Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.
A cyclin D subtype which is regulated by GATA4 TRANSCRIPTION FACTOR. Experiments using KNOCKOUT MICE suggest a role for cyclin D2 in granulosa cell proliferation and gonadal development.
A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.
A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.
A cyclin subtype that is specific for CYCLIN-DEPENDENT KINASE 4 and CYCLIN-DEPENDENT KINASE 6. Unlike most cyclins, cyclin D expression is not cyclical, but rather it is expressed in response to proliferative signals. Cyclin D may therefore play a role in cellular responses to mitogenic signals.
A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.
A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.
A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.
A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.
A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.
Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
A cyclin G subtype that is constitutively expressed throughout the cell cycle. Cyclin G1 is considered a major transcriptional target of TUMOR SUPPRESSOR PROTEIN P53 and is highly induced in response to DNA damage.
A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.
The B-cell leukemia/lymphoma-1 genes, associated with various neoplasms when overexpressed. Overexpression results from the t(11;14) translocation, which is characteristic of mantle zone-derived B-cell lymphomas. The human c-bcl-1 gene is located at 11q13 on the long arm of chromosome 11.
A cyclin subtype that binds to the CYCLIN-DEPENDENT KINASE 3 and CYCLIN-DEPENDENT KINASE 8. Cyclin C plays a dual role as a transcriptional regulator and a G1 phase CELL CYCLE regulator.
Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.
A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.
A cyclin B subtype that colocalizes with GOLGI APPARATUS during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 9. Unlike traditional cyclins, which regulate the CELL CYCLE, type T cyclins appear to regulate transcription and are components of positive transcriptional elongation factor B.
Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).
A cyclin subtype that is found as a component of a heterotrimeric complex containing cyclin-dependent kinase 7 and CDK-activating kinase assembly factor. The complex plays a role in cellular proliferation by phosphorylating several CYCLIN DEPENDENT KINASES at specific regulatory threonine sites.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
An unusual cyclin subtype that is found highly expressed in terminally differentiated cells. Unlike conventional cyclins increased expression of cyclin G2 is believed to cause a withdrawal of cells from the CELL CYCLE.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A cell line derived from cultured tumor cells.
A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
A cyclin subtype that is found abundantly in post-mitotic tissues. In contrast to the classical cyclins, its level does not fluctuate during the cell cycle.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
A quiescent state of cells during G1 PHASE.
A form of non-Hodgkin lymphoma having a usually diffuse pattern with both small and medium lymphocytes and small cleaved cells. It accounts for about 5% of adult non-Hodgkin lymphomas in the United States and Europe. The majority of mantle-cell lymphomas are associated with a t(11;14) translocation resulting in overexpression of the CYCLIN D1 gene (GENES, BCL-1).
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Established cell cultures that have the potential to propagate indefinitely.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.
A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS.
Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
A CELL CYCLE and tumor growth marker which can be readily detected using IMMUNOCYTOCHEMISTRY methods. Ki-67 is a nuclear antigen present only in the nuclei of cycling cells.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Tumors or cancer of the human BREAST.
A family of proteins that share the F-BOX MOTIF and are involved in protein-protein interactions. They play an important role in process of protein ubiquition by associating with a variety of substrates and then associating into SCF UBIQUITIN LIGASE complexes. They are held in the ubiquitin-ligase complex via binding to SKP DOMAIN PROTEINS.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.
A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from http://www.atcc.org/)
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
A transcription factor that possesses DNA-binding and E2F-binding domains but lacks a transcriptional activation domain. It is a binding partner for E2F TRANSCRIPTION FACTORS and enhances the DNA binding and transactivation function of the DP-E2F complex.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A negative regulator of the CELL CYCLE that undergoes PHOSPHORYLATION by CYCLIN-DEPENDENT KINASES. It contains a conserved pocket region that binds E2F4 TRANSCRIPTION FACTOR and interacts with viral ONCOPROTEINS such as POLYOMAVIRUS TUMOR ANTIGENS; ADENOVIRUS E1A PROTEINS; and PAPILLOMAVIRUS E7 PROTEINS.
A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
A ubiquitously expressed regulatory protein that contains a retinoblastoma protein binding domain and an AT-rich interactive domain. The protein may play a role in recruiting HISTONE DEACETYLASES to the site of RETINOBLASTOMA PROTEIN-containing transcriptional repressor complexes.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
A family of structurally-related proteins that were originally identified by their ability to complex with cyclin proteins (CYCLINS). They share a common domain that binds specifically to F-BOX MOTIFS. They take part in SKP CULLIN F-BOX PROTEIN LIGASES, where they can bind to a variety of F-BOX PROTEINS.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.
Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
Elements of limited time intervals, contributing to particular results or situations.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.
MAMMARY GLANDS in the non-human MAMMALS.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
An aspect of protein kinase (EC 2.7.1.37) in which serine residues in protamines and histones are phosphorylated in the presence of ATP.
Transport proteins that carry specific substances in the blood or across cell membranes.
A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION.
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)
Regulatory signaling systems that control the progression of the CELL CYCLE through the G1 PHASE and allow transition to S PHASE when the cells are ready to undergo DNA REPLICATION. DNA DAMAGE, or the deficiencies in specific cellular components or nutrients may cause the cells to halt before progressing through G1 phase.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
Protein kinase that drives both the mitotic and meiotic cycles in all eukaryotic organisms. In meiosis it induces immature oocytes to undergo meiotic maturation. In mitosis it has a role in the G2/M phase transition. Once activated by CYCLINS; MPF directly phosphorylates some of the proteins involved in nuclear envelope breakdown, chromosome condensation, spindle assembly, and the degradation of cyclins. The catalytic subunit of MPF is PROTEIN P34CDC2.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Family of retrovirus-associated DNA sequences (myc) originally isolated from an avian myelocytomatosis virus. The proto-oncogene myc (c-myc) codes for a nuclear protein which is involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Truncation of the first exon, which appears to regulate c-myc expression, is crucial for tumorigenicity. The human c-myc gene is located at 8q24 on the long arm of chromosome 8.
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
Processes required for CELL ENLARGEMENT and CELL PROLIFERATION.
Gated transport mechanisms by which proteins or RNA are moved across the NUCLEAR MEMBRANE.
A multifunctional CDC2 kinase-related kinase that plays roles in transcriptional elongation, CELL DIFFERENTIATION, and APOPTOSIS. It is found associated with CYCLIN T and is a component of POSITIVE TRANSCRIPTIONAL ELONGATION FACTOR B.
A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.
A family of proteins that are structurally-related to Ubiquitin. Ubiquitins and ubiquitin-like proteins participate in diverse cellular functions, such as protein degradation and HEAT-SHOCK RESPONSE, by conjugation to other proteins.
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
Echinoderms having bodies of usually five radially disposed arms coalescing at the center.
A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.
The process by which a DNA molecule is duplicated.
An E2F transcription factor that represses GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F4 recruits chromatin remodeling factors indirectly to target gene PROMOTER REGIONS through RETINOBLASTOMA LIKE PROTEIN P130 and RETINOBLASTOMA LIKE PROTEIN P107.
Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN and the alpha-amino groups of LYSINE residues in the protein. The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex of enzymes can be broken down into three components that involve activation of ubiquitin (UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex (UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES).
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.

Coupling of the cell cycle and myogenesis through the cyclin D1-dependent interaction of MyoD with cdk4. (1/3253)

Proliferating myoblasts express the muscle determination factor, MyoD, throughout the cell cycle in the absence of differentiation. Here we show that a mitogen-sensitive mechanism, involving the direct interaction between MyoD and cdk4, restricts myoblast differentiation to cells that have entered into the G0 phase of the cell cycle under mitogen withdrawal. Interaction between MyoD and cdk4 disrupts MyoD DNA-binding, muscle-specific gene activation and myogenic conversion of 10T1/2 cells independently of cyclin D1 and the CAK activation of cdk4. Forced induction of cyclin D1 in myotubes results in the cytoplasmic to nuclear translocation of cdk4. The specific MyoD-cdk4 interaction in dividing myoblasts, coupled with the cyclin D1-dependent nuclear targeting of cdk4, suggests a mitogen-sensitive mechanism whereby cyclin D1 can regulate MyoD function and the onset of myogenesis by controlling the cellular location of cdk4 rather than the phosphorylation status of MyoD.  (+info)

Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (2/3253)

The irreversible G1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). We show that the Cdk inhibitor p21(Sdi1,Cip1,Waf1), which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active. Furthermore, the senescent-cell-cycle arrest occurs prior to the accumulation of the Cdk4-Cdk6 inhibitor p16(Ink4a), suggesting that p21 may be sufficient for this event. Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16. Instead, the cyclin D1-Cdk4 and cyclin D1-Cdk6 complexes in these cells are associated with an increased amount of p21, suggesting that p21 may be responsible for inactivation of both cyclin E- and cyclin D1-associated kinase activity at the early stage of senescence. Moreover, even in the late stage of senescence when p16 is high, cyclin D1-Cdk4 complexes are persistent, albeit reduced by +info)

Progesterone inhibits estrogen-induced cyclin D1 and cdk4 nuclear translocation, cyclin E- and cyclin A-cdk2 kinase activation, and cell proliferation in uterine epithelial cells in mice. (3/3253)

The response of the uterine epithelium to female sex steroid hormones provides an excellent model to study cell proliferation in vivo since both stimulation and inhibition of cell proliferation can be studied. Thus, when administered to ovariectomized adult mice 17beta-estradiol (E2) stimulates a synchronized wave of DNA synthesis and cell division in the epithelial cells, while pretreatment with progesterone (P4) completely inhibits this E2-induced cell proliferation. Using a simple method to isolate the uterine epithelium with high purity, we have shown that E2 treatment induces a relocalization of cyclin D1 and, to a lesser extent, cdk4 from the cytoplasm into the nucleus and results in the orderly activation of cyclin E- and cyclin A-cdk2 kinases and hyperphosphorylation of pRb and p107. P4 pretreatment did not alter overall levels of cyclin D1, cdk4, or cdk6 nor their associated kinase activities but instead inhibited the E2-induced nuclear localization of cyclin D1 to below the control level and, to a lesser extent, nuclear cdk4 levels, with a consequent inhibition of pRb and p107 phosphorylation. In addition, it abrogated E2-induced cyclin E-cdk2 activation by dephosphorylation of cdk2, followed by inhibition of cyclin A expression and consequently of cyclin A-cdk2 kinase activity and further inhibition of phosphorylation of pRb and p107. P4 is used therapeutically to oppose the effect of E2 during hormone replacement therapy and in the treatment of uterine adenocarcinoma. This study showing a novel mechanism of cell cycle inhibition by P4 may provide the basis for the development of new antiestrogens.  (+info)

Insertion of excised IgH switch sequences causes overexpression of cyclin D1 in a myeloma tumor cell. (4/3253)

Oncogenes are often dysregulated in B cell tumors as a result of a reciprocal translocation involving an immunoglobulin locus. The translocations are caused by errors in two developmentally regulated DNA recombination processes: V(D)J and IgH switch recombination. Both processes share the property of joining discontinuous sequences from one chromosome and releasing intervening sequences as circles that are lost from progeny cells. Here we show that these intervening sequences may instead insert in the genome and that during productive IgH mu-epsilon switch recombination in U266 myeloma tumor cells, a portion of the excised IgH switch intervening sequences containing the 3' alpha-1 enhancer has inserted on chromosome 11q13, resulting in overexpression of the adjacent cyclin D1 oncogene.  (+info)

Alternatively spliced EDA segment regulates fibronectin-dependent cell cycle progression and mitogenic signal transduction. (5/3253)

Fibronectin (FN) is comprised of multiple isoforms arising from alternative splicing of a single gene transcript. One of the alternatively spliced segments, EDA, is expressed prominently in embryonic development, malignant transformation, and wound healing. We showed previously that EDA+ FN was more potent than EDA- FN in promoting cell spreading and cell migration because of its enhanced binding affinity to integrin alpha5beta1 (Manabe, R., Oh-e, N., Maeda, T., Fukuda, T., and Sekiguchi, K. (1997) J. Cell Biol. 139, 295-307). In this study, we compared the cell cycle progression and its associated signal transduction events induced by FN isoforms with or without the EDA segment to examine whether the EDA segment modulates the cell proliferative potential of FN. We found that EDA+ FN was more potent than EDA- FN in inducing G1-S phase transition. Inclusion of the EDA segment potentiated the ability of FN to induce expression of cyclin D1, hyperphosphorylation of pRb, and activation of mitogen-activated protein kinase extracellular signal regulated kinase 2 (ERK2). EDA+ FN was also more potent than EDA- FN in promoting FN-mediated tyrosine phosphorylation of p130(Cas), but not focal adhesion kinase, which occurred in parallel with the activation of ERK2, suggesting that p130(Cas) may be involved in activation of ERK2. These results indicated that alternative splicing at the EDA region is a novel mechanism that promotes FN-induced cell cycle progression through up-regulation of integrin-mediated mitogenic signal transduction.  (+info)

Survey of gene amplifications during prostate cancer progression by high-throughout fluorescence in situ hybridization on tissue microarrays. (6/3253)

Prostate cancer development and progression is driven by the accumulation of genetic changes, the nature of which remains incompletely understood To facilitate high-throughput analysis of molecular events taking place in primary, recurrent, and metastat prostate cancer, we constructed a tissue microarray containing small 0.6-mm cylindrical samples acquired from 371 formalin-fixed blocks, including benign prostatic hyperplasia (n = 32) and primary tumors (n = 223), as well as both locally recurrent tumors (n = 54) and metastases (n = 62) from patients with hormone-refractory disease. Fluorescence in situ hybridization (FISH) was applied to the analysis of consecutive tissue microarray sections with probes for five different genes. High-level (> or =3X) amplifications were very rare (<2%) in primary prostate cancers However, in metastases from patients with hormone-refractory disease, amplification of the androgen receptor gene was seen in 22%, MYC in 11%, and Cyclin-D1 in 5% of the cases. In specimens from locally recurrent tumors, the corresponding percentages were 23, 4, and 8%. ERBB2 and NMYC amplifications were never detected at any stage of prostate cancer progression. In conclusion, FISH to tissue microarray sections enables high-throughput analysis of genetic alterations contributing to cancer development and progression. Our results implicate a role for amplification of androgen receptor in hormonal therapy failure and that of MYC in the metastatic progression of human prostate cancer.  (+info)

Alterations of Rb pathway (Rb-p16INK4-cyclin D1) in preinvasive bronchial lesions. (7/3253)

Lung cancer results from a stepwise accumulation of genetic and molecular abnormalities with unknown temporal relationships to precursor bronchial lesions. In a search for biomarkers of malignant progression, we analyzed the expression of the tumor suppressor gene Rb and of the proteins regulating its phosphorylation and function in G1 arrest, p16INK4A and cyclin D1, in preinvasive bronchial lesions accompanying cancer in 75 patients, in comparison with similar lesions in 22 patients with no cancer history. Rb was constantly expressed in preinvasive lesions, including carcinoma in situ (CIS). In contrast, p16 expression was lost in moderate dysplasia (12%) and in CIS (30%) in patients with lung cancer. p16 loss occurred exclusively in patients who displayed loss of p16 expression in their related invasive carcinoma. Loss of p16 expression was not seen in nine patients with dysplasia but no cancer progression. Cyclin D1 overexpression was seen in hyperplasia and metaplasia (6%), mild dysplasia (17%), moderate dysplasia (46%), and CIS (38%) in patients with cancer but was lost in 5% of the patients during the process of invasion; it was also observed in patients with no cancer progression (14%). Our results indicate that Rb protein function can be invalidated before invasion through alteration of the Rb phosphorylation pathway, by p16 inhibition, and/or by cyclin D1 overexpression and suggest a role for p16 and cyclin D1 deregulation in progression of preinvasive bronchial lesions to invasive carcinoma.  (+info)

Cyclin D1 proteolysis: a retinoid chemoprevention signal in normal, immortalized, and transformed human bronchial epithelial cells. (8/3253)

BACKGROUND: Retinoids (derivatives of vitamin A) are reported to reduce the occurrence of some second primary cancers, including aerodigestive tract tumors. In contrast, beta-carotene does not reduce the occurrence of primary aerodigestive tract cancers. Mechanisms explaining these effective retinoid and ineffective carotenoid chemoprevention results are poorly defined. Recently, the all-trans-retinoic acid (RA)-induced proteolysis of cyclin D1 that leads to the arrest of cells in G1 phase of the cell cycle was described in human bronchial epithelial cells and is a promising candidate for such a mechanism. In this study, we have investigated this proteolysis as a common signal used by carotenoids or receptor-selective and receptor-nonselective retinoids. METHODS: We treated cultured normal human bronchial epithelial cells, immortalized human bronchial epithelial cells (BEAS-2B), and transformed human bronchial epithelial cells (BEAS-2BNNK) with receptor-selective or receptor-nonselective retinoids or with carotenoids and studied the effects on cell proliferation by means of tritiated thymidine incorporation and on cyclin D1 expression by means of immunoblot analysis. We also examined whether calpain inhibitor I, an inhibitor of the 26S proteasome degradation pathway, affected the decline (i.e., proteolysis) of cyclin D1. RESULTS: Receptor-nonselective retinoids were superior to the carotenoids studied in mediating the decline in cyclin D1 expression and in suppressing the growth of bronchial epithelial cells. Retinoids that activated retinoic acid receptor beta or retinoid X receptor pathways preferentially led to a decrease in the amount of cyclin D1 protein and a corresponding decline in growth. The retinoid-mediated degradation of cyclin D1 was blocked by cotreatment with calpain inhibitor I. CONCLUSIONS: Retinoid-dependent cyclin D1 proteolysis is a common chemoprevention signal in normal and neoplastic human bronchial epithelial cells. In contrast, carotenoids did not affect cyclin D1 expression. Thus, the degradation of cyclin D1 is a candidate intermediate marker for effective retinoid-mediated cancer chemoprevention in the aerodigestive tract.  (+info)

PURPOSE: We analyzed the expression of critical cell cycle regulators cyclin E and cyclin D1 in familial breast cancer, focusing on BRCA mutation-negative tumors. Cyclin E expression in tumors of BRCA1 or BRCA2 carriers is higher, and cyclin D1 expression lower, than in sporadic tumors. In familial non-BRCA1/2 tumors, cyclin E and cyclin D1 expression has not been studied. EXPERIMENTAL DESIGN: Cyclin E and cyclin D1 immunohistochemical expression was studied in tissue microarrays consisting of 53 BRCA1, 58 BRCA2, 798 familial non-BRCA1/2, and 439 sporadic breast tumors. RESULTS: In univariate analysis, BRCA1 tumors had significantly more frequently high cyclin E (88%) and low cyclin D1 (84%) expression than sporadic (54% and 49%, respectively) or familial non-BRCA1/2 (38% and 45%, respectively) tumors. BRCA2 tumors had significantly more frequently low cyclin D1 expression (68%) than sporadic or familial non-BRCA1/2 tumors and significantly more frequently high cyclin E expression than familial ...
TY - JOUR. T1 - Cyclin D1 is not an immediate target of beta-catenin following Apc loss in the intestine.. AU - Sansom, O.J.. AU - Reed, K.R.. AU - Wetering, M.van de. AU - Muncan, V.. AU - Winston, D.. AU - Clevers, J.C.. AU - Clarke, A.R.. N1 - doi: 10.1074/jbc.M500191200. PY - 2005. Y1 - 2005. N2 - Cyclin D1 is postulated to be a target of the canonical Wnt pathway and critical for intestinal adenoma development. We show here that, unlike cyclin D1 reporter assays, endogenous cyclin D1 levels are not affected following antagonism of the Wnt pathway in vitro, nor is cyclin D1immediately up-regulated following conditional loss of Apc in vivo. Cyclin D1 levels do, however, increase in a delayed manner in a small subset of cells, suggesting such up-regulation occurs as a secondary event. We also analyzed the immediate consequences of Apc loss in a cyclin D1(-/-) background and failed to find any cyclin D1-dependent phenotypes. However, we did observe elevated cyclin D1 expression in lesions ...
Cyclin D1 is a G1-specific cyclin that has been linked to lymphoid, parathyroid, and breast tumors. Recent studies suggested that high protein levels of cyclin D1 are not always produced when cyclin D1 mRNA is overexpressed in transfected cells, suggesting that posttranscriptional events may be important in cyclin D1 regulation. The mRNA cap-binding protein (eukaryotic initiation factor 4E [eIF-4E]) is a potential regulatory of several posttranscriptional events, and it can itself induce neoplastic transformation. Consequently, we examined eIF-4E as a potential regulator of cyclin D1. Overexpression of cyclin D1 mRNA in NIH 3T3 cells did not increase cyclin D1 protein. In contrast, overexpression of eIF-4E markedly increased the amount of cyclin D1 protein in NIH 3T3 cells. This increase was specific to cyclin D1 in comparison with the retinoblastoma gene product, c-Myc, actin, and eukaryotic initiation factor 2 alpha. We also examined cyclin D1 protein in cells expressing an estrogen ...
The treatment of quiescent cells with growth factors results in the transcriptional activation of the D-type cyclin genes during G1. Expression of the members of this family of cyclins, D1, 2 and 3, is spatially and temporally regulated with respect to growth factor receptor ligation. Transcription of these particular cyclins is proposed to monitor the growth factor signal and the encoded proteins participate in G1 progression. I have been defining the cis-acting elements and trans-acting factors that control transcription of the human cyclin D3 gene in T-cells. Genomic clones for the human cyclin D3 gene, isolated from a human chromosome 6 library, were analysed by restriction endonuclease digestion and a sub-clone extending 1.7kb upstream of exon 1 was sequenced and studied. The human cyclin D3 gene has a TATA-less promoter and a single dominant initiation site. The minimal cyclin D3 promoter sequence was identified as a region 173bp upstream of the transcription initiation site. Transient ...
Cyclin D1 is an important cell cycle regulator but in cancer its overexpression also increases cellular migration mediated by p27KlP1 stabilization and RhoA inhibition. Recently, a common polymorphism at the exon 4-intron 4 boundary of the human cyclin D1 gene within a splice donor region was associated with an altered risk of developing cancer. Altered RNA splicing caused by this polymorphism gives rise to a variant cyclin D1 isoform termed cyclin D1b, which has the same N-terminus as the canonical cyclin D1a isoform but a distinct C-terminus. In this study we show that these different isoforms have unique properties with regard to the cellular migration function of cyclin D1. Whereas they displayed little difference in transcriptional co-repression assays on idealized reporter genes, microarray cDNA expression analysis revealed differential regulation of genes including those that influence cellular migration. Additionally, while cyclin D1a stabilized p27KIP1 and inhibited RhoA-induced ROCK kinase
TY - JOUR. T1 - Interaction between the pRb2/p130 C-terminal domain and the N-terminal portion of cyclin D3. AU - Bonetto, Francesco. AU - Fanciulli, Maurizio. AU - Battista, Tullio. AU - De Luca, Antonio. AU - Russo, Patrizia. AU - Bruno, Tiziana. AU - De Angelis, Roberta. AU - Di Padova, Monica. AU - Giordano, Antonio. AU - Felsani, Armando. AU - Paggi, Marco C.. PY - 1999/12/15. Y1 - 1999/12/15. N2 - An association between cyclin D3 and the C-terminal domain of pRb2/p130 was demonstrated using the yeast two-hybrid system. Further analysis restricted the epitope responsible for the binding within the 74 N-terminal amino acids of cyclin D3, independent of the LXCXE amino acid motif present in the D-type cyclin N-terminal region. In a coprecipitation assay in T98G cells, a human glioblastoma cell line, the C-terminal domain of pRb2/p130 was able to interact solely with cyclin D3, while the corresponding portion of pRb interacted with either cyclin D3 or cyclin D1. In T98G cells, endogenous ...
FIG.9. Effects of UV stimulation on cyclin D1 and p52. (A) UV treatment down regulates cyclin D1 protein levels. U-2 OS cells were treated with 40-J/m2 UV radiation for the indicated times. Whole-cell lysates were prepared and immunoblotted for cyclin D1 and a β-actin control as indicated. (B) UV treatment inhibits the cyclin D1 promoter in a manner dependent upon the proximal κB element. One and a half micrograms of each of the cyclin D1 (−66) and cyclin D1 (−66 mut) luciferase reporter plasmids were transfected into U-2 OS cells. Cells were treated with 40-J/m2 UV radiation for 6 h as indicated. Results are expressed as change in activation or repression (n-fold) relative to levels seen in the relevant untreated cell controls. luc, luciferase. (C) UV treatment induces Ser-15 phosphorylated endogenous p53 and down regulates Bcl-3 levels. U-2 OS cells were treated with 40-J/m2 UV radiation for the indicated times. Nuclear protein extracts were prepared and immunoblotted for p53, ...
Expression profile and molecular genetic regulation of cyclin D1 expression in epithelioid sarcoma Epithelioid sarcoma is a distinctive, aggressive soft tissue tumor typically presenting as a subcutaneous or deep dermal mass in the distal extremities of young adults. Molecular genetic data of well-characterized cases of epithelioid sarcoma are sparse. A recent cytogenetic study of epithelioid sarcoma by conventional metaphase comparative genomic hybridization reported recurrent gains at chromosome 11q13, a region containing many genes, including the cyclin D1 gene. Cyclin D1 is a positive cell cycle regulator that is overexpressed in a variety of neoplasms, including mantle cell lymphoma and breast carcinoma. The objective of this study was to examine cyclin D1 expression in epithelioid sarcoma. Of 24 cases evaluated, 23 (96%) displayed cyclin D1 nuclear expression using immunohistochemical evaluation. Eight cases, which expressed cyclin D1 by immunohistochemistry, were evaluated by fluorescence ...
The protein encoded by the Bcl-1 oncogene, known as cyclin D1, belongs to the highly conserved family of cyclin-dependent kinase (CDK) regulators. It is also known as CCND1, B-cell lymphoma 1 protein (BCL1), parathyroid adenomatosis 1 (PRAD1), B-cell CLL/lymphoma 1, G1/S-specific cyclin-D1, D11S287E, and U21B31. Different cyclins exhibit distinct expression and degradation patterns that contribute to the coordination of the cell cycle during mitosis. Cyclin D1 interacts with CDK4 and CDK6, whose activity is required for the cell cycle G1/S transition. Cyclin D1 also interacts with tumor suppressor protein Rb. Mutations in the Bcl-1 gene are associated with a variety of cancers, including esophageal, breast, and bladder cancer, as well as a variety of B-cell-related leukemias and lymphomas.. ...
Aberrant expression of cyclin D1, frequently observed in human malignant disorders, has been linked to the control of G1→S cell cycle phase transition and development and progression in carcinogenesis. Cyclin D1 level changes are partially controlled by GSK-3β-dependent phosphorylation at threonine-286 (Thr286), which targets cyclin D1 for ubiquitination and proteolytic degradation. In our continuing studies on the mechanism of prostate cancer prevention by resveratrol, focusing on the role of its recently discovered target protein, quinone reductase 2 (NQO2), we generated NQO2 knockdown CWR22Rv1 using short hairpin RNA (shRNA)-mediated gene silencing approach. We found that, compared with cells expressing NQO2 (shRNA08), NQO2 knockdown cells (shRNA25) displayed slower proliferation and G1 phase cell accumulation. Immunoblot analyses revealed a significant decrease in phosphorylation of retinoblastoma Rb and cyclin D1 in shRNA25 compared with shRNA08. Moreover, shRNA25 cells showed a 37% ...
TY - JOUR. T1 - Prognostic role of cyclin d1 in lung cancer relationship to proliferating cell nuclear antigen. AU - Caputi, Mario. AU - Groeger, Angela M.. AU - Esposito, Vincenzo. AU - Dean, Charity. AU - De Luca, Antonio. AU - Pacilio, Carmen. AU - Muller, Michael R.. AU - Giordano, Giovan G.. AU - Baldi, Feliciano. AU - Wolner, Ernst. AU - Giordano, Antonio. PY - 1999. Y1 - 1999. N2 - We developed an immunohistochemical assay specific for cyclin D1 and suitable for formalin-fixed and paraffin-embedded sections, to evaluate cyclin D1 expression in a group of 135 surgically resected lung-cancer patients for the purpose of investigating the prognostic role of this protein in lung cancer. In addition, we compared cyclin D1 expression with the expression of proliferating cell nuclear antigen (PCNA), considered to be a reliable index of the proliferation rate. We found cyclin D1 expressed in more than 60% of the neoplastic cells in 26.5% of our specimens. A total of 24.5% of the specimens showed ...
Data Availability StatementData are contained inside the paper. analysis from the transcriptional activity for ATF3, Wnt or NF-B. siRNA for ATF3 or p65 was employed for the knockdown of ATF3 and p65. Outcomes TC-HW decreased the cell viability in individual colorectal cancers cells. TC-HW reduced cyclin D1 proteins level through cyclin D1 degradation via GSK3-reliant threonine-286 (T286) phosphorylation of cyclin D1, indicating that cyclin D1 degradation might donate to TC-HW-mediated loss of cyclin D1 protein level. TC-HW downregulated the appearance of cyclin D1 mRNA level and Rabbit polyclonal to AREB6 inhibited Wnt activation through the downregulation of -catenin and TCF4 manifestation, indicating that inhibition of cyclin D1 transcription may also result in TC-HW-mediated decrease of cyclin D1 protein level. In addition, TC-HW was observed to induce apoptosis through ROS-dependent DNA damage. TC-HW-induced ROS improved NF-B and ATF3 activation, and inhibition of NF-B and ATF3 activation ...
and a shift of cyclin D1 mRNA from the polysome-associated to free mRNA fraction, indicating that 15d-PGJ2 inhibits the initiation of cyclin D1 mRNA translation. The selective rapid decrease in cyclin D1 protein accumulation is facilitated by its rapid turnover (t1/2=34 min) after inhibition of cyclin D1 protein synthesis. The half-life of cyclin D1 protein is not significantly altered in cells treated with 15d-PGJ2. Treatment of cells with 15d-PGJ2 results in strong induction of heat shock protein 70 (HSP70) gene expression, suggesting that 15d-PGJ2 might activate protein kinase R (PKR), an eIF- ...
THE D-type cyclins (D1, D2 and D3) are critical governors of the cell-cycle clock apparatus during the G1 phase of the mammalian cell cycle. These three D-type cyclins are expressed in overlapping, apparently redundant fashion in the proliferating tissues. To investigate why mammalian cells need three distinct D-type cyclins, we have generated mice bearing a disrupted cyclin D2 gene by using gene targeting in embryonic stem cells. Cyclin D2-deficient females are sterile owing to the inability of ovarian granulosa cells to proliferate normally in response to follicle-stimulating hormone (FSH), whereas mutant males display hypoplastic testes. In ovarian granulosa cells, cyclin D2 is specifically induced by FSH via a cyclic-AMP-dependent pathway, indicating that expression of the various D-type cyclins is under control of distinct intracellular signalling pathways. The hypoplasia seen in cyclin D2(-/-) ovaries and testes prompted us to examine human cancers deriving from corresponding tissues.
Metabolism of L-Arg by arginase I-producing MDSCs leads to a significant decrease in the extracellular levels of L-Arg in murine tumor models and in patients with cancer (5, 25). The decreased levels of L-Arg induced the prolonged loss in the expression of CD3ζ (7, 26) and inhibited T cell proliferation (8). These effects were not associated with the induction of apoptosis and were rapidly reversible after replenishment of L-Arg or citrulline (8). We recently showed that activated primary T cells cultured in the absence of L-Arg were arrested in the G0-G1 phase of the cell cycle (8). The G0-G1 arrest in the cell cycle observed in L-Arg-deprived T cells correlated with an inability to upregulate the expression of cyclin D3 (8). Results from cyclin D3 knockout mice had demonstrated that cyclin D3 is essential for the maturation of T cells in the thymus (27), and they suggested a potential and selective role in T cell proliferation. Additionally, silencing of cyclin D3 induced a similar inhibition ...
Cyclin D1 is an oncogene frequently overexpressed in human cancers that has a dual function as cell cycle and transcriptional regulator, although the latter is widely unexplored. Here, we investigated the transcriptional role of cyclin D1 in lymphoid tumor cells with cyclin D1 oncogenic overexpression. Cyclin D1 showed widespread binding to the promoters of most actively transcribed genes, and the promoter occupancy positively correlated with the transcriptional output of targeted genes. Despite this association, the overexpression of cyclin D1 in lymphoid cells led to a global transcriptional downmodulation that was proportional to cyclin D1 levels. This cyclin D1-dependent global transcriptional downregulation was associated with a reduced nascent transcription and an accumulation of promoter-proximal paused RNA polymerase II (Pol II) that colocalized with cyclin D1. Concordantly, cyclin D1 overexpression promoted an increase in the Poll II pausing index. This transcriptional impairment seems ...
As described above, we have reported a new physiological function of Cyclin D2 in the neuronal development of the mouse. We next questioned whether this mechanism is conserved among mammalian species. In humans, we found an accumulation of Cyclin D2 protein at the basal side of the cortical primordium at gestation week 16 (Tsunekawa et al. 2012). We also noted that the cis-acting element identified in mice that promotes basal transportation is highly conserved in human (74% match in the National Center for Biotechnology Information [NCBI] database). Therefore, it is tempting to speculate that in the human cortical primordium, Cyclin D2 mRNA is similarly transported within the basal process toward the basal endfoot and locally translated into protein. Notably, the basal transport cis-element that we have identified appears to be unique to mammals, as similar sequences are not found in avians or amphibians (NCBI database). Similarly, no accumulation of Cyclin D2 mRNA in the basal side of the chick ...
...(PHILADELPHIA) Cyclin D1 a protein that helps push a replicating cel... In addition to its role in regulating the cell cycle cyclin D1 induc...Using antisense RNA Dr. Pestells group was the first to show that cy...In the current study the group sought to investigate the mechanism by...,Cyclin,D1,governs,microRNA,processing,in,breast,cancer,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
B-cell lymphoma gene (BCL-6) upregulation contributes to immortalization of mouse embryo fibroblast and primary B cells via upregulation of cyclin D1. As cyclin D1 overexpression is a common phenomenon in different cancers, BCL-6 protein overexpression may not be restricted to lymphomas. In this study, expression of BCL-6 was investigated by immunohistochemistry on ... read more paraffin-embedded specimens from 150 breast cancer patients and 10 specimens of normal breast tissue. The results showed BCL-6 overexpression (X10% of cells) in 24/150 (16%) breast cancer patients, whereas in normal breast low expression (o1%) of BCL-6 was observed. In linear regression analysis BCL-6 expression was associated with cyclin D1 (r=0.197, P=0.016). Further, in v2 analyses, BCL-6-positivity was associated with overexpression of p53 (P=0.016), and hypoxia-inducible factor-1a (P,0.001). Involvement of BCL-6 in breast carcinogenesis is further underscored by comparative genomic hybridization analysis that showed ...
The alternatively spliced cyclin D1b variant of the CCND1 gene has been proposed to have higher oncogenic potential than cyclin D1a (8, 9). In breast cancer, aberrant cyclin D1b expression confers resistance to therapeutic treatment (30) and is associated with poor prognosis in patients (31). Cyclin D1b was also recently shown to enhance cell invasiveness and anchorage-independent growth of bladder cancer cells (32), and this isoform has been detected in various other cancer types (8, 28, 33). In PCa, changes in the cyclin D1b/cyclin D1a ratio are of particular relevance. Indeed, whereas both isoforms support cell cycle progression, they behave differently in the interaction with the AR pathway. Cyclin D1a was reported to associate with AR and to negatively regulate its transcriptional activity, thereby representing a brake for uncontrolled proliferation of PCa cells (6). By contrast, this negative feedback function is lacking in cyclin D1b (11), and its expression positively correlated with PCa ...
Smad nuclear interacting protein 1 (SNIP1) is an evolutionarily conserved protein containing a forkhead-associated (FHA) domain that regulates gene expression through interactions with multiple transcriptional regulators. Here, we have used short interfering RNAs (siRNAs) to knockdown SNIP1 expression in human cell lines. Surprisingly, we found that reduction in SNIP1 levels resulted in significantly reduced cell proliferation and accumulation of cells in the G1 phase of the cell cycle. Consistent with this result, we observed that cyclin D1 protein and mRNA levels were reduced. Moreover, SNIP1 depletion results in inhibition of cyclin D1 promoter activity in a manner dependent upon a previously characterized binding site for the AP-1 transcription factor family. SNIP1 itself is induced upon serum stimulation immediately prior to cyclin D1 expression. These effects were independent of the tumour suppressors p53 and retinoblastoma (Rb), but were consistent with an interaction with BRG1, a component of
BACKGROUND: To investigate markers for predicting breast cancer progression, we performed a candidate gene-based study that assessed expression change of three genes, cyclin D1, β-catenin, and metastasis-associated protein-1 (MTA1), involving in aggressive phenotypes of cancerous cells, namely hyperproliferation, epithelial-mesenchymal transition, and global transcriptional regulation.. METHODS: Specimens were from 150 enrolled female patients, with invasive ductal carcinoma, followed up for more than 10 years. mRNA expression of cyclin D1, β-catenin, and MTA1 in cancerous and noncancerous cells microdissected from the primary tumor site was determined by quantitative real-time PCR. The relationship between mRNA expression levels of the genes and clinicopathologic features was assessed by statistical analysis. Disease-free and overall survival (DFS and OS) were analyzed by Kaplan-Meier analysis with log-rank test and a multivariate Cox regression model.. RESULTS: Cyclin D1 was shown to be ...
These events induce a proliferative hereditary program (Shape 2) thats appropriately controlled during mammary gland development but clearly becomes deleterious when recapitulated and deregulated in cancer cells expressing abundant cyclin D1. Understanding the functional linkage between PRs and cell pattern regulatory proteins such as for example cyclins and CDKs might provide novel focuses on to prevent or reverse the looks of early lesions and halt cell pattern progression in hormonally controlled breasts tumors. cyclin D1 copurified in whole-cell lysates of transiently transfected COS-1 cells and in PR-positive T47D breasts cancers cells expressing endogenous cyclin D1. PRs, cyclin D1, and SP1 had been recruited towards the promoter in progestin-treated T47D breasts cancers cells. Mutation of PR Ser345 to Ala (S345A) or inhibition of CDK2 activity using roscovitine disrupted PR/cyclin D1 relationships with DNA and clogged mRNA manifestation. Discussion of phosphorylated PRs with SP1 and ...
购买经敲除验证的重组Cyclin D1兔单克隆抗体[EP272Y](ab40754),Cyclin D1抗体经WB,IP验证,可与人,小鼠,大鼠样本反应。8篇文献引用,4个独立用户反馈。
Malignant gliomas frequently show genetic aberrations of genes coding for cell cycle regulatory proteins involved in the control of G1/S phase transition. These include mutation and/or deletion of the retinoblastoma (RB1) gene, homozygous deletion of the CDKN2A and CDKN2B genes, as well as amplification and overexpression of the CDK4 and CDK6 genes. The D‐type cyclins (cyclin D1, D2, and D3) promote cell cycle progression from G1 to S phase by binding to and activating the cyclin dependent kinases Cdk4 and Cdk6. Here, we have investigated a series of 110 primary malignant gliomas and 8 glioma cell lines for amplification and expression of the D‐type cyclin genes CCND1 (11q13), CCND2 (12p13), and CCND3 (6p21). We found the CCND1 gene amplified and overexpressed in one anaplastic astrocytoma of our tumor series. Two glioblastomas and one anaplastic astrocytoma showed CCND2 gene amplification, but lacked significant overexpression of CCND2 transcripts. Amplification and overexpression of the ...
Plasmid -962 human cyclin D1 promoter EtsB site mutant pGL3Basic from Dr. Frank McCormicks lab contains the insert CCND1 and is published in Nature. 1999 Apr 1;398(6726):422-6. This plasmid is available through Addgene.
The generation of robust T-cell-dependent humoral immune responses requires the formation and expansion of germinal center structures within the follicular regions of the secondary lymphoid tissues. was only observed in mature GCs (Fig. ?(Fig.5D).5D). These data correlate with the lack of cyclin D2 manifestation in adult GCs and the requirement for cyclin D3 specifically at this stage. Based on our observation that cyclin D3 transcripts were observed in both follicular and GC B cells whereas cyclin D3 protein was only detected in GC cells and previous reports showing that cyclin D3 was regulated by pre-BCR mediated inhibition of proteosomal degradation (7) we hypothesized that GC-specific signaling events promote cyclin D3 protein stability. The proteosomal degradation of D-type cyclins upon phosphorylation of a conserved threonine residue by GSK3α/β has been previously reported (10). In addition phosphorylation of GSK3α/β on serine 21/9 residues leads to reduced kinase activity (27). We ...
The generation of robust T-cell-dependent humoral immune responses requires the formation and expansion of germinal center structures within the follicular regions of the secondary lymphoid tissues. was only observed in mature GCs (Fig. ?(Fig.5D).5D). These data correlate with the lack of cyclin D2 manifestation in adult GCs and the requirement for cyclin D3 specifically at this stage. Based on our observation that cyclin D3 transcripts were observed in both follicular and GC B cells whereas cyclin D3 protein was only detected in GC cells and previous reports showing that cyclin D3 was regulated by pre-BCR mediated inhibition of proteosomal degradation (7) we hypothesized that GC-specific signaling events promote cyclin D3 protein stability. The proteosomal degradation of D-type cyclins upon phosphorylation of a conserved threonine residue by GSK3α/β has been previously reported (10). In addition phosphorylation of GSK3α/β on serine 21/9 residues leads to reduced kinase activity (27). We ...
Cyclin D1 expression is induced by Sox17.(A-B) Immunohistochemistry for cyclin D1 was performed on lung sections from adult CCSPrtTA (A) and CCSPrtTA/tetO-Sox
Plasmid pIS1 Cyclin D2 short UTR from Dr. David Bartels lab contains the insert Cyclin D2 short UTR and is published in Cell. 2009 Aug 21. 138(4):673-84. This plasmid is available through Addgene.
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Cyclin D1 is a target for positive regulation by estrogens in growth-responsive cells, in which it mediates their mitogenic effects. Amplification and overexpression of the cyclin D1 gene (CCND1) might thus represent a genetic lesion inducing hormone-independent growth of transformed cells. Indeed, cyclin D1 overexpression has been found in up to 50% of primary breast cancers, and in about one-third of these cases, this is linked to amplification of the 11q13 chromosomal region, which also includes the CCND1 gene. These tumors are predominantly estrogen receptor-positive, and for this reason, these patients are often selected for adjuvant antiestrogen therapy. No information is available, however, as to whether cyclin D1 overexpression due to gene amplification might interfere with and reduce antiestrogen efficacy. This was investigated here by taking advantage of an experimental model that reproduces cyclin D1 overexpression resulting from increased CCND1 gene dosage in hormone-responsive human ...
The cyclin D1 expression pattern is not altered by signaling inhibitors. If the PI3K/AKT/GSK3 pathway stabilizes cyclin D1 levels specifically during G1 and G2 phases as suggested above, inhibitors of this pathway would produce a reduction in cyclin D1 expression during these cell cycle phases to the low levels seen during S phase. Thus, inhibition of these signaling pathways would be expected to result in low, uniform expression of cyclin D1 throughout the cell cycle. PI3K was inhibited by LY294002, while the kinase mTOR was inhibited by rapamycin in actively cycling human diploid fibroblast (MRC5) cultures. After 2 hrs treatment, including a terminal pulse with BrdU, the culture was fixed and stained with fluorescent antibodies against both cyclin D1 and BrdU, while DNA was stained with DAPI. Individual images of each fluorochrome were collected with a sensitive CCD camera, and subjected to image analysis to accurately quantitate the level of each fluorochrome in each cell (see [20]). The ...
B78 Growth arrest represents an innate barrier to carcinogenesis. DNA damage and replicational stress are known to induce growth arrest and apoptotic death to avert genomic instability and consequently carcinogenesis. Working on the genotoxic stress induced by hydroxyurea and methylmethanesulfone, we observed a growth arrest at G1/S-phase that was mediated by destabilization of cyclin D1. The growth arrest was independent of the stability of cdc25A and preceded transcriptional up-regulation of p21waf1. Cyclin D1 destabilization involved its phosphorylation by GSK-3beta at threonine-286 since overexpression of the kinase-dead mutant of GSK-3beta or cyclin D1T286A mutant conferred stability to cyclin D1. Further, overexpression of cyclin D1T286A also helped in bypassing G1/S phase growth arrest. We also observed a rapid inactivation of Akt/PKB kinase in the presence of hydroxyurea. Enforced expression of the constitutively active Akt or viral oncoprotein HBx was sufficient to overcome growth ...
Alterations in cell cycle regulators have been implicated in human malignancies including breast cancer. PD 0332991 is an orally active, highly selective inhibitor of the cyclin D kinases (CDK)4 and CDK6 with ability to block retinoblastoma (Rb) phosphorylation in the low nanomolar range. To identify predictors of response, we determined the in vitro sensitivity to PD 0332991 across a panel of molecularly characterized human breast cancer cell lines. Forty-seven human breast cancer and immortalized cell lines representing the known molecular subgroups of breast cancer were treated with PD 0332991 to determine IC50 values. These data were analyzed against baseline gene expression data to identify genes associated with PD 0332991 response. Cell lines representing luminal estrogen receptor-positive (ER+) subtype (including those that are HER2 amplified) were most sensitive to growth inhibition by PD 0332991 while nonluminal/basal subtypes were most resistant. Analysis of variance identified 450
TY - JOUR. T1 - Identification of interaction partners and substrates of the cyclin A1-CDK2 complex. AU - Diederichs, Sven. AU - Bäumer, Nicole. AU - Ji, Ping. AU - Metzelder, Stephan K.. AU - Idos, Gregory E.. AU - Cauvet, Thomas. AU - Wang, Wenbing. AU - Möller, Maria. AU - Pierschalski, Sarah. AU - Gromoll, Jörg. AU - Schrader, Mark G.. AU - Koeffler, H. Phillip. AU - Berdel, Wolfgang E.. AU - Serve, Hubert. AU - Müller-Tidow, Carsten. PY - 2004/8/6. Y1 - 2004/8/6. N2 - The CDK2-associated cyclin A1 is essential for spermatogenesis and contributes to leukemogenesis. The detailed molecular functions of cyclin A1 remain unclear, since the molecular networks involving cyclin A1-CDK2 have not been elucidated. Here, we identified novel cyclin A1/CDK2 interaction partners in a yeast triple-hybrid approach. Several novel proteins (INCA1, KARCA1, and PROCA1) as well as the known proteins GPS2 (G-protein pathway suppressor 2), Ku70, receptor for activated protein kinase C1/guanine ...
We report the isolation of UME3, a C‐type cyclin that is required for the full repression of several early meiotic genes (e.g. SPO13) and SSA1, a member of the HSP70 superfamily. Similarly to other cyclin C family members, UME3 mRNA and protein levels remained unchanged throughout the mitotic cell cycle. However, under conditions that induce SSA1 or SPO13 transcription, we demonstrate that Ume3p is subjected to degradation. This destruction is required for normal meiotic gene induction, as a mutation that stabilizes Ume3p resulted in a 2‐fold reduction in SPO13 mRNA accumulation. These findings reveal the first observed regulation of a C‐type cyclin. Moreover, the destruction of Ume3p in response to heat shock or developmental cues represents a new set of regulatory signals by which any cyclin is controlled. We identified three cis‐acting domains (PEST‐rich, RXXL and the cyclin box) that contribute to the destruction of Ume3p during heat shock. In cultures exposed to heat shock, Ume3p ...
Citation: Soni R. and Chaudhuri B. (2001) Cell cycle arrest mediated by a pyridopyrimidine is not abrogated by over-expression of Bcl-2 and cyclin D1. International Journal of Oncology. 18 (5) pp.1035-40 ...
Supplementary Materials Supplemental Data supp_285_5_3510__index. aspect BB-induced cyclin D1 promoter-luciferase reporter gene activity. Furthermore to its function in cell routine development, cyclin D1 mediated HASMC migration within an NFATc1-reliant way. Balloon injury-induced cyclin D1-CDK4 activity needs NFAT activation, and adenovirus-mediated transduction of cyclin D1 was discovered to be enough to get over the blockade aftereffect […]. ...
The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of cyclin-dependent kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. Knockout studies of the homologous gene in mouse suggest the essential roles of this gene in ovarian granulosa and germ cell proliferation. High level expression of this gene was observed in ovarian and testicular tumors.[2] ...
Cyclin A2 activates the cyclin-dependent kinases Cdk1 and Cdk2 and is expressed at elevated levels from S phase until early mitosis. We found that mutant mice that cannot elevate cyclin A2 are chromosomally unstable and tumor-prone. Underlying the chromosomal instability is a failure to up-regulate the meiotic recombination 11 (Mre11) nuclease in S phase, which leads to impaired resolution of stalled replication forks, insufficient repair of double-stranded DNA breaks, and improper segregation of sister chromosomes. Unexpectedly, cyclin A2 controlled Mre11 abundance through a C-terminal RNA binding domain that selectively and directly binds Mre11 transcripts to mediate polysome loading and translation. These data reveal cyclin A2 as a mechanistically diverse regulator of DNA replication combining multifaceted kinase-dependent functions with a kinase-independent, RNA binding-dependent role that ensures adequate repair of common replication errors. ...
Mouse Monoclonal Anti-Cyclin D1 Antibody (DCS-6). G1-Cyclin & Mantle Cell Marker. Validated: WB, ELISA, Flow, ICC/IF, IHC-Fr, IHC-P, IP, PAGE. Tested Reactivity: Human, Mouse, Rat, and more. 100% Guaranteed.
Amino acids S11 - H267 (end residue is R580) of human Cyclin K. Residue S232 of the fusion protein is equivalent to S11 of the native enzyme. The GST tag is located at residues 1 - 220 ...
Amino acids M1 - S341 (end) of human Cyclin Y. Residue M232 of the fusion protein is equivalent to M1 of the native enzyme. The GST tag is located at residues 1 - 220 ...
Monoclonal clone# G2 antibody for CYCLIN D2/CCND2 detection. Host: Mouse.Size: 100μg/vial. Tested applications: ICC. Reactive species: Human. CYCLIN D2/CCND2 information: Molecular Weight: 32826 MW; Subcellular Localization: Nucleus . Cytoplasm . Membran
context : http://schema.org, @type : Product, name : Rat Cyclin D1 ELISA Kit, image : https://www.elisagenie.com/product_images/k/085/ER0328__34855.jpg, description : Rat Cyclin D1 ELISA Kit assay has a sensitivity of 0.094ng/ml ...
The cyclin E oncogene activates CDK2 to drive cells from G1 to S phase of the cell cycle to commence DNA replication. It coordinates essential cellular functions with the cell cycle including histone biogenesis, splicing, centrosome duplication and origin firing for DNA replication. The two E-cyclins, E1 and E2, are assumed to act interchangeably in these functions. However recent reports have identified unique functions for cyclins E1 and E2 in different tissues, and particularly in breast cancer. Cyclins E1 and E2 localise to distinct foci in breast cancer cells as well as co-localising within the cell. Both E-cyclins are found in complex with CDK2, at centrosomes and with the splicing machinery in nuclear speckles. However cyclin E2 uniquely co-localises with NPAT, the main activator of cell-cycle regulated histone transcription. Increased cyclin E2, but not cyclin E1, expression is associated with high expression of replication-dependent histones in breast cancers. The preferential localisation of
Results Normal epidermis showed parabasal Ki67 and cyclin D1 staining while fascin labelled cells in the lower one-third of the epithelium. Reactive and dVIN specimens demonstrated mildly increased Ki67 and cyclin D1 expression that maintained parabasal polarity, whereas uVIN and p16-positive SCC were characterised by loss of cyclin D1 staining. However, in 14 of 20 p16-positive SCC small infiltrative tumour groups and single infiltrating cells at the invasive front showed a cyclin D1-positive/ Ki67-negative phenotype. In contrast, p16-negative SCC generally showed diffuse and concordant cyclin D1 and Ki67 labelling, including at the invasive margin. Fascin expression was increased in all VIN and SCC lesions.. ...
Cyclin E is one of the key regulators of the G(1)/S transition in the cell cycle. Overexpression of cyclin E has been observed in several malignancies and is associated with high proliferation, aberrant expression of other cell cycle regulators and chromosomal instability in vitro. To explore potential associations between cyclin E deregulation and inactivation of the p53 tumor suppressor gene in human breast cancer, we investigated the immunohistochemical expression of cyclin E in paraffin embedded breast cancers from 270 women with known p53 status by cDNA based sequencing of the p53 gene. The breast cancers were divided into three subgroups according to the percentage of cyclin E-positive cells. One hundred and seventy-one patients (63%) had low cyclin E, 72 (27%) medium and 27 (10%) had high cyclin E content. Fifty-six percent (15/27) of the breast cancers with high cyclin E had p53 gene mutations, compared with 14% (24/171) of those with low cyclin E content (P , 0.0001). In p53 mutated ...
TY - JOUR. T1 - PKCα tumor suppression in the intestine is associated with transcriptional and translational inhibition of cyclin D1. AU - Pysz, Marybeth A.. AU - Leontieva, Olga V.. AU - Bateman, Nicholas W.. AU - Uronis, Joshua M.. AU - Curry, Kathryn J.. AU - Threadgill, David W.. AU - Janssen, Klaus Peter. AU - Robine, Sylvie. AU - Velcich, Anna. AU - Augenlicht, Leonard H.. AU - Black, Adrian R.. AU - Black, Jennifer D.. PY - 2009/5/1. Y1 - 2009/5/1. N2 - Alterations in PKC isozyme expression and aberrant induction of cyclin D1 are early events in intestinal tumorigenesis. Previous studies have identified cyclin D1 as a major target in the antiproliferative effects of PKCα in non-transformed intestinal cells; however, a link between PKC signaling and cyclin D1 in colon cancer remained to be established. The current study further characterized PKC isozyme expression in intestinal neoplasms and explored the consequences of restoring PKCα or PKCδ in a panel of colon carcinoma cell lines. ...
The present study was conducted to analyze the alterations affecting cyclins D1, E, and A in bilharzial bladder cancer and to assess their potential clinical significance. A total of 125 cases were examined. Histopathological subtypes included 68 squamous cell carcinomas, 55 transitional cell carcinomas, and 2 adenocarcinomas. Immunohistochemical analyses were performed using a panel of well-characterized antibodies. The results were correlated with proliferative index, as assessed by Ki67 antigen expression. The cyclin D1-positive phenotype, defined as the identification of positive immunoreactivity in the nuclei of ,/=20% of tumor cells, was found in 33 of 107 (31%) evaluable cases. A significant association was observed between the cyclin D1-positive phenotype and deep muscle invasion (P = 0.02), high tumor grade (P = 0.02), and Ki67 high proliferative index (P = 0.03). The cyclin E-positive phenotype, defined as per cyclin D1, was found in 79 of 106 (75%) evaluable cases. The cyclin ...
Although mutations that activate the Hedgehog (Hh) signalling pathway have been linked to several types of cancer, the molecular and cellular basis of Hhs ability to induce tumour formation is not well understood. We identified a mutation in patched (ptc), an inhibitor of Hh signalling, in a genetic screen for regulators of the Retinoblastoma (Rb) pathway in Drosophila. Here we show that Hh signalling promotes transcription of Cyclin E and Cyclin D, two inhibitors of Rb, and principal regulators of the cell cycle during development in Drosophila. Upregulation of Cyclin E expression, accomplished through binding of Cubitus interruptus (Ci) to the Cyclin E promoter, mediates the ability of Hh to induce DNA replication. Upregulation of Cyclin D expression by Hh mediates the distinct ability of Hh to promote cellular growth. The discovery of a direct connection between Hh signalling and principal cell-cycle regulators provides insight into the mechanism by which deregulated Hh signalling promotes ...
In contrast to cyclin D1 and D2, the expression level of cyclin D3 was high in the hindbrain at the E15.5 stage (Figure 3I, arrowhead). Moreover, in the midbrain cyclin D3 was expressed in cells closer to the ventricle than those expressing cyclin D2 (Figure 3H, I, arrows).. Discussion. At the E10.5 stage, all three D-type cyclins were expressed in most of the spinal cord cells but cyclin D1 and D3 showed higher expression levels in the dorsal half of the spinal cord. Wianny et al. (1998) found that the dorso-ventral gradient of the cyclin D1 transcript also occurs in the spinal cord of 7-9 somite-stage embryos. However, in our study we found that at the E10.5 stage cyclin D2 was not missing from the floor plate and also that cyclin D3 was not expressed only ventrally, as was reported for the transcripts of the genes in 7-9 somite stage embryos by Wianny et al. (1998). This may have been due to altered expression patterns of these genes during the time course of spinal cord development and ...
The G1 cyclins, cyclin D1 and E, are rate limiting for progression through G1 phase of the cell cycle in breast epithelial cells and are oncogenic when expressed in the mammary epithelium of transgenic mice. These genes are frequently overexpressed in clinical breast cancer where overexpression appears to be associated with specific disease phenotypes, altered responsiveness to therapeutic intervention and patient survival. In order to investigate the functional correlates of cyclin D1 and cyclin E overexpression we employed a panel of normal, immortalized and neoplastic breast epithelial cell lines to examine the relationships between cyclin gene expression, cyclin-CDK complex formation and CDK activity. In agreement with earlier studies cyclin D1 and E expression varied over an approximately tenfold range among the 18 cell lines studied. There was no apparent relationship, however, between cyclin D1 expression and the in vitro activity of its major kinase partner, Cdk4, although MDA-MB-134 cells
Severe and prolonged cytopenias represent a considerable problem in clinical stem cell transplantations. Cytokine-induced ex vivo expansion of hematopoietic stem and progenitor cells has been intensively explored as a means of accelerating hematopoietic recovery following transplantation but have so far had limited success. Herein, overexpression of D-type cyclins, promoting G0/G1 to S transition, was investigated as an alternative approach to accelerate myeloid reconstitution following stem cell transplantation. With the use of retroviral-mediated gene transfer, cyclin D2 was overexpressed in murine bone marrow progenitor cells, which at limited doses showed enhanced ability to rescue lethally ablated recipients. Competitive repopulation studies demonstrated that overexpression of cyclin D2 accelerated myeloid reconstitution following transplantation, and, in agreement with this, cyclin D2-transduced myeloid progenitors showed an enhanced proliferative response to cytokines in vitro. Furthermore,
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Progestin antagonists inhibit the proliferation of progesterone receptor-positive cells, including breast cancer cells, by G1 phase-specific actions, but the molecular targets involved are not defined. Reduced phosphorylation of pRB, a substrate for G1 cyclin-dependent kinases (CDKs) in vivo, was apparent after 9 h treatment of T-47D breast cancer cells with the antiprogestins RU 486 or ORG 31710, accompanying changes in S phase fraction. Although the abundance of cyclin D1, Cdk4, and Cdk6 did not decrease cyclin D1-associated kinase activity was reduced by approximately 50% at 9-18 h. Similarly, cyclin E-associated kinase activity decreased by approximately 60% at 12-24 h in the absence of significant changes in the abundance of cyclin E and Cdk2. The CDK inhibitor p21 increased in mRNA and protein abundance and was present at increased levels in cyclin D1 and cyclin E complexes at times when their kinase activity was decreased. Increased p21 protein abundance was observed in another antiprogestin
Transforming growth factor-β (TGF-β) signaling members, TGF-β receptor type II (TBRII), Smad2, Smad4 and Smad adaptor, embryonic liver fodrin (ELF), are prominent tumor suppressors in gastrointestinal cancers. Here, we show that 40% of elf+/- mice spontaneously develop hepatocellular cancer (HCC) with markedly increased cyclin D1, cyclin-dependent kinase 4 (Cdk4), c-Myc and MDM2 expression. Reduced ELF but not TBRII, or Smad4 was observed in 8 of 9 human HCCs (P|0.017). ELF and TBRII are also markedly decreased in human HCC cell lines SNU-398 and SNU-475. Restoration of ELF and TBRII in SNU-398 cells markedly decreases cyclin D1 as well as hyperphosphorylated-retinoblastoma (hyperphosphorylated-pRb). Thus, we show that TGF-β signaling and Smad adaptor ELF suppress human hepatocarcinogenesis, potentially through cyclin D1 deregulation. Loss of ELF could serve as a primary event in progression toward a fully transformed phenotype and could hold promise for new therapeutic approaches in human HCCs. ©
The relative levels of cyclin D1 (CCND1) (a) and (b) transcripts were determined by real-time reverse transcription polymerase chain reaction (RT-PCR) and found to vary according to the tissue origin in both control and tumor samples. A five-fold overexpression of both isoforms was observed in 28/38 cases of mantle cell lymphoma (MCL) and of only one isoform in 10/38 MCL. No correlation was observed between expression of cyclin D1 isoforms and CCND1 genotype at position 870. ...
Chromosomal instability (CIN) in tumors is characterized by chromosomal abnormalities and an altered gene expression signature; however, the mechanism of CIN is poorly understood. CCND1 (which encodes cyclin D1) is overexpressed in human malignancies and has been shown to play a direct role in transcriptional regulation. Here, we used genome-wide ChIP sequencing and found that the DNA-bound form of cyclin D1 occupied the regulatory region of genes governing chromosomal integrity and mitochondrial biogenesis. Adding cyclin D1 back to Ccnd1-/- mouse embryonic fibroblasts resulted in CIN gene regulatory region occupancy by the DNA-bound form of cyclin D1 and induction of CIN gene expression. Furthermore, increased chromosomal aberrations, aneuploidy, and centrosome abnormalities were observed in the cyclin D1-rescued cells by spectral karyotyping and immunofluorescence. To assess cyclin D1 effects in vivo, we generated transgenic mice with acute and continuous mammary gland-targeted cyclin D1 ...
Jang S.W., Liu X., Fu H., Rees H., Yepes M., Levey A., Ye K.. Terminally differentiated neurons are unable to reenter the cell cycle. Aberrant cell cycle activation provokes neuronal cell death, whereas cell cycle inhibition elevates neuronal survival. However, the molecular mechanism regulating the cell cycle and cell death in mature neurons remains elusive. Here we show that SRPK2, a protein kinase specific for the serine/arginine (SR) family of splicing factors, triggers cell cycle progression in neurons and induces apoptosis through regulation of nuclear cyclin D1. Akt phosphorylates SRPK2 on Thr-492 and promotes its nuclear translocation leading to cyclin D1 up-regulation, cell cycle reentry, and neuronal apoptosis. In addition, SRPK2 phosphorylates SC35 and, thus, inactivates p53, resulting in cyclin D1 up-regulation. 14-3-3 binding to SRPK2, regulated by Akt phosphorylation, inhibits these events. We find that SRPK2 is phosphorylated in ischemia-attacked brain, correlating with the ...
Overexpressed cyclin E in tumours is a prognosticator for poor patient outcome. Cells that overexpress cyclin E have been shown to be impaired in S-phase progression and exhibit genetic instability that may drive this subset of cancers. However, the
Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13.
TY - JOUR. T1 - Mantle cell lymphoma with a novel t(11;12)(q13;p11.2). T2 - a proposed alternative mechanism of CCND1 up-regulation. AU - Menke, Joshua R.. AU - Vasmatzis, George. AU - Murphy, Stephen. AU - Yang, Lin. AU - Menke, David M.. AU - Tun, Han W. AU - King, Rebecca. AU - Smoley, Stephanie A.. AU - Ketterling, Rhett P.. AU - Sukov, William R.. PY - 2017/6/1. Y1 - 2017/6/1. N2 - Mantle cell lymphoma (MCL) is typically characterized by t(11;14), which places the [email protected] enhancer elements upstream of CCND1. This fusion results in up-regulation of CCND1 and consequently its protein product cyclin D1. Recent studies have shown that in MCL, mutations or translocations occurring within the 3′ untranslated region (UTR) of the CCND1 gene can result in a truncated mRNA transcript that is more stable and associated with more aggressive disease. We identified a case of MCL showing cyclin D1 overexpression by immunohistochemistry and a t(11;12)(q13;p11.2) by conventional cytogenetic studies. ...
In response to DNA damage, eukaryotic cells initiate a complex signalling pathway, termed the DNA damage response (DDR), which coordinates cell cycle arrest with DNA repair. Studies have shown that oncogene-induced senescence, which provides a barrier to tumour development, involves activation of the DDR. Using a genome-wide RNA interference (RNAi) screen, we have identified 17 factors required for oncogenic BRAF to induce senescence in primary fibroblasts and melanocytes. One of these factors is an F-box protein, FBXO31, a candidate tumour suppressor encoded in 16q24.3, a region in which there is loss of heterozygosity in breast, ovarian, hepatocellular and prostate cancers. Here we study the cellular role of FBXO31, identify its target substrate and determine the basis for its growth inhibitory activity. We show that ectopic expression of FBXO31 acts through a proteasome-directed pathway to mediate the degradation of cyclin D1, an important regulator of progression from G1 to S phase, resulting in
Cell proliferation is regulated by the balance between cyclin-dependent kinases (CDKs) and CDK inhibitors such as p27. In neonatal cardiomyocytes, p27 is a key inhibitor of cell proliferation (6) and cyclin D1 is important for cell cycle progression (36). To delineate the pathway through which TIMP-3 inhibits neonatal cardiomyocyte proliferation, the effect of TIMP-3 on cyclin D1 and p27 expression was investigated. Our data showed that cyclin D1 was increased in TIMP-3−/− cardiomyocytes and decreased in rTIMP-3-treated cells as compared with WT. Consistent with these results, p27 expression was decreased in the TIMP-3−/− cardiomyocytes and neonatal hearts as compared with WT. This decrease in p27 expression resulted in an increase in cardiomyocyte proliferation both in vitro and in vivo. Furthermore, treatment of cardiomyocytes with rTIMP-3 resulted in a significant increase in p27 expression, which led to a significant decrease in cardiomyocyte proliferation. Our data suggest that ...
Home » meis1 regulates cyclin D1 and c-myc expression, and controls the proliferation of the multipotent cells in the early developing zebrafish ...
The transcription factor GATA-2 is critical regulator of hematopoietic stem and progenitor cell (HSPC) development and function, and mutations in the enhancer region of GATA2 are linked to blood disorders. In this episode, Emery Bresnick and colleagues develop and characterize a mouse model that harbors a human disease-associated GATA2 enhancer mutation. In this model, hematopoietic development and function were normal unless the animals were exposed to a secondary stress that necessitated blood cell regeneration. The results of this study provide important insight into GATA-2-dependent pathogenesis.. ...
Pathogenic remodeling following heart injury is due, in part, to the limited regenerative capacity of adult cardiomyocytes. Cell cycle induction has been recently explored as a therapeutic approach for heart failure, and to this end, expression of cyclin D2 in cardiomyocytes improves outcomes in mouse models follwoing myocardial infarction. In this episode, Gerd Hasenfuß, Loren Field, and Karl Toischer discuss their collaborative effort to further evaluate the effect of increased cyclin D2 on outcomes in response to other forms of heart failure. Cyclin D2 expression improved survival and cardiac function in mice exposed to pressure overload; however, cyclin D2-espressing mice were not protected from adverse effects in response to chronic volume overload. These results support further effort into the development of strategies to improve cardiomyocyte proliferation for some types cardiac injury.. ...
Pathogenic remodeling following heart injury is due, in part, to the limited regenerative capacity of adult cardiomyocytes. Cell cycle induction has been recently explored as a therapeutic approach for heart failure, and to this end, expression of cyclin D2 in cardiomyocytes improves outcomes in mouse models follwoing myocardial infarction. In this episode, Gerd Hasenfuß, Loren Field, and Karl Toischer discuss their collaborative effort to further evaluate the effect of increased cyclin D2 on outcomes in response to other forms of heart failure. Cyclin D2 expression improved survival and cardiac function in mice exposed to pressure overload; however, cyclin D2-espressing mice were not protected from adverse effects in response to chronic volume overload. These results support further effort into the development of strategies to improve cardiomyocyte proliferation for some types cardiac injury.. ...
Pathogenic remodeling following heart injury is due, in part, to the limited regenerative capacity of adult cardiomyocytes. Cell cycle induction has been recently explored as a therapeutic approach for heart failure, and to this end, expression of cyclin D2 in cardiomyocytes improves outcomes in mouse models follwoing myocardial infarction. In this episode, Gerd Hasenfuß, Loren Field, and Karl Toischer discuss their collaborative effort to further evaluate the effect of increased cyclin D2 on outcomes in response to other forms of heart failure. Cyclin D2 expression improved survival and cardiac function in mice exposed to pressure overload; however, cyclin D2-espressing mice were not protected from adverse effects in response to chronic volume overload. These results support further effort into the development of strategies to improve cardiomyocyte proliferation for some types cardiac injury.. ...
Pathogenic remodeling following heart injury is due, in part, to the limited regenerative capacity of adult cardiomyocytes. Cell cycle induction has been recently explored as a therapeutic approach for heart failure, and to this end, expression of cyclin D2 in cardiomyocytes improves outcomes in mouse models follwoing myocardial infarction. In this episode, Gerd Hasenfuß, Loren Field, and Karl Toischer discuss their collaborative effort to further evaluate the effect of increased cyclin D2 on outcomes in response to other forms of heart failure. Cyclin D2 expression improved survival and cardiac function in mice exposed to pressure overload; however, cyclin D2-espressing mice were not protected from adverse effects in response to chronic volume overload. These results support further effort into the development of strategies to improve cardiomyocyte proliferation for some types cardiac injury.. ...
Pathogenic remodeling following heart injury is due, in part, to the limited regenerative capacity of adult cardiomyocytes. Cell cycle induction has been recently explored as a therapeutic approach for heart failure, and to this end, expression of cyclin D2 in cardiomyocytes improves outcomes in mouse models follwoing myocardial infarction. In this episode, Gerd Hasenfuß, Loren Field, and Karl Toischer discuss their collaborative effort to further evaluate the effect of increased cyclin D2 on outcomes in response to other forms of heart failure. Cyclin D2 expression improved survival and cardiac function in mice exposed to pressure overload; however, cyclin D2-espressing mice were not protected from adverse effects in response to chronic volume overload. These results support further effort into the development of strategies to improve cardiomyocyte proliferation for some types cardiac injury.. ...
The smooth progression of the eukaryotic cell cycle relies on the periodic activation of members of a family of cell cycle kinases by regulatory proteins called cyclins. Outside of the cell cycle, cyclin homologs play important roles in regulating the assembly of transcription complexes; distant structural relatives of the conserved cyclin core or box can also function as general transcription factors (like TFIIB) or survive embedded in the chain of the tumor suppressor, retinoblastoma protein. The present work attempts the prediction of the canonical secondary, supersecondary, and tertiary fold of the minimal cyclin box domain using a combination of techniques that make use of the evolutionary information captured in a multiple alignment of homolog sequences. A tandem set of closely packed, helical modules are predicted to form the cyclin box domain.
ABSTRACT: A modified version of a previously developed mathematical model [Obeyesekere et al., Cell Prolif. (1997)] of the G1-phase of the cell cycle is presented. This model describes the regulation of the G1-phase that includes the interactions of the nuclear proteins, RB, cyclin E, cyclin D, cdk2, cdk4 and E2F. The effects of the growth factors on cyclin D synthesis under saturated or unsaturated growth factor conditions are investigated based on this model. The solutions to this model (a system of nonlinear ordinary differential equations) are discussed with respect to existing experiments. Predictions based on mathematical analysis of this model are presented. In particular, results are presented on the existence of two stablesolutions, i.e., bistability within the G1-phase. It is shown that this bistability exists under unsaturated growth factor concentration levels. This phenomenon is very noticeable if the efficiency of the signal transduction, initiated by the growth factors leading to ...
The effect was found to be associated with increased expression of E2F-1 in cervical cancer cells as there is no CAPE-mediated induction of E2F-1 in the precancerous cervical Z172 cells. CAPE also upregulated the E2F-1 target genes cyclin A, cyclin E, and apoptotic protease activation of factor 1 (Apaf-1) but down regulated cyclin B and myeloid leukemia cell differentiation protein (Mcl-1). These results suggested the involvement of E2F-1 in CAPE-mediated growth inhibition and cell cycle arrest. Transient transfection studies with luciferase reporters revealed that CAPE altered transcriptional activity of the apaf-1 and mcl-1 promoters. Further studies using chromatin immunoprecipitation (ChIP) assays demonstrated that in CAPE-treated cells, E2F-1 binding to the apaf-1 and cyclin B promoters was increased and decreased, respectively. Furthermore, E2F-1 silencing abolished CAPE-mediated effects on cell cycle arrest, apoptosis, and related gene expression ...
Cyclin E2, but not cyclin E1, is included in several gene signatures that predict disease progression in either tamoxifen-resistant or metastatic breast cancer. We therefore examined the role of cyclin E2 in antiestrogen resistance in vitro and its potential for therapeutic targeting through cyclin- …
Using two endometrial cancer cell lines, IL11Rα blockade reduced IL11 action, but there was a blunted functional response in grade 1 Ishikawa endometrial cancer-derived cells compared with grade 2 HEC1A cells, likely due to differences in IL11 ligand production and/or IL11Rα expression levels between the cell lines. IL11Rα blockade only transiently reduced Ishikawa cell proliferation in vitro and tumor growth in vivo. When protein levels of cyclin D3 were determined, hIL11Rα antibody treatment downregulated this established IL11-regulated cell-cycle target (21,25) in HEC1A tumors compared with IgG control. However, there was no effect of IL11Rα inhibition on cyclin D3 levels in Ishikawa tumors. This finding coincided with a more profound reduction in HEC1A cell proliferation in response to IL11 blockade in vitro, compared with Ishikawa cells. Both Ishikawa and HEC1A cells are responsive to exogenous IL11, as shown previously by STAT3 activation (22). However, as Ishikawa cells endogenously ...
The reasons for increased levels of CyD1 mRNA in cases with predominance of the truncated variant probably lie in the destabilizing function of the 3UTR, which contains AU-rich elements, which are crucial for regulating mRNA stability.36 Genes with long 3UTR such as CyD1 usually encode for short-lived proteins involved in proliferation and other tightly regulated, transient cellular functions.37 In addition, truncation of the 3UTR of the CyD1 mRNA results in loss of miR-16-1 binding sites and may change regulation of CyD1 protein expression.38. Although the predominance of the short CyD1 isoform in MCL is common - 23% in our series, similar to the 18% observed by Wiestner et al. - the reasons for this are evident only in a minority of cases.19 Only 6% of MCL lacked the long canonical transcript completely, and in only half of these cases were we able to demonstrate a genomic deletion of the 3UTR explaining the complete loss of expression. Since previously described mutations introducing stop ...
This product is specific for Cyclin D1, a member of the cyclin family that function as CKD reculators. Cyclin D1 is involved in cell cycle transition and has been shown to interact with the retinoblastoma protein. The unprocessed precursor is 295 amino acids long. It is expressed in abnormally high levels in a number of cancers and is specifically implicated in breast cancer development ...
We report several novel observations. First, we find that multiple cdk4/6 and D-cyclin combinations can robustly stimulate human β-cell replication in vitro. Surprisingly, among all of the possible cdk4/6-D-cyclin combinations, cyclin D3 appeared to be a particularly effective partner for cdk6 and cdk4. Second, we demonstrate that, although cyclin D2 is a very effective partner for both cdk4 and cdk6 in stimulating human β-cell replication, and despite its being both present and essential for rodent β-cell replication and function, it is only marginally detectable in human β-cells. Third, we observe that the D-cyclins and cdks 4 and 6 are principally cytosolic proteins in the human β-cell. Fourth, we report that a single member of the cdk4/6 D-cyclin complex, cdk6, is able to enhance human β-cell transplantation in vivo. Fifth, we demonstrate that human β-cell replication can be sustained in vivo for at least four weeks using cdk6.. The rapid proliferation induced by the D3 combinations ...
CCNE1 / Cyclin E1 Protein LS-G97233 is a Recombinant Human CCNE1 / Cyclin E1 produced in Baculovirus Met 1-Ala 410 with His tag(s). It is low in endotoxin; Less than 1.0 EU/µg protein (determined by LAL method).
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Although most efforts to develop antagonists of CDK function have focused on identifying and optimizing ATP-competitive CDK inhibitors, a number of studies have been published in which new, creative strategies have been used. Most of these approaches focus on CDK2 inhibition. This is in part due to the fact that X-ray crystal structures of CDK2 and the cyclin A/CDK2 complex have been available longer than similar data for other CDK and cyclin/CDK complexes. A crystal structure of cyclin A/CDK2 in complex with ATP and a substrate peptide (Brown et al., 1999) (Fig. 3A) shows ATP bound in a cleft formed on one side by the GEGTYG nucleotide-binding motif (red- and blue-colored residues). The peptide substrate is bound in a cleft adjacent to the ATP binding site and in close apposition to ATP. Interestingly, binding of the endogenous CDK inhibitor p27 to cyclin A/CDK2 causes large-scale structural changes to the cyclin A/CDK2 complex (Fig. 3B) (Russo et al., 1996). p27 inserts itself into the ATP ...
An Intron-Retaining Splice Variant of Human Cyclin A2, Expressed in Adult Differentiated Tissues, Induces a G1-S Cell Cycle Arrest In Vitro. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
References for Abcams Recombinant Human Cyclin E1 protein (ab119719). Please let us know if you have used this product in your publication
Whereas many components regulating the progression from S phase through G2 phase into mitosis have been identified, the mechanism by which these components control this critical cell cycle progression is still not fully elucidated. Cyclin A/Cdk2 has
The overexpression of cyclin D1 is thought to be a major factor in the development of ISMCL and its progression to MCL. ... The cyclin D1-expressing lymphocytes generally populate the inner layers of the marginal zone but on occasion some of these ... "CCND1 cyclin D1 [Homo sapiens (human)] - Gene - NCBI". "TP53 tumor protein p53 [Homo sapiens (human)] - Gene - NCBI". "CDKN2B ... In consequence, CCND1 overexpresses cyclin D1, a protein which promotes the cell cycle and thereby cellular proliferation. ...
Jiang Q, Feng MG, Mo YY (June 2009). "Systematic validation of predicted microRNAs for cyclin D1". BMC Cancer. 9: 194. doi: ...
It has been shown to activate the cell division cycle 2, cyclin D1, and insulin-like growth factor-binding protein 5 genes. ... Horstmann S, Ferrari S, Klempnauer KH (January 2000). "Regulation of B-Myb activity by cyclin D1". Oncogene. 19 (2): 298-306. ... April 2001). "Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at functionally important serine ... The encoded protein is phosphorylated by cyclin A/cyclin-dependent kinase 2 during the S-phase of the cell cycle and possesses ...
LKB1 catalytic deficient mutants found in Peutz-Jeghers Syndrome activate the expression of cyclin D1 through recruitment to ... Scott KD, Nath-Sain S, Agnew MD, Marignani PA (June 2007). "LKB1 catalytically deficient mutants enhance cyclin D1 expression ...
Jiang Q, Feng MG, Mo YY (2009). "Systematic validation of predicted microRNAs for cyclin D1". BMC Cancer. 9: 194. doi:10.1186/ ...
AKAP13 AHR BRCA1 CAV1 CCNC CDC25B CEBPB COBRA1 COUP-TFI CREBBP CRSP3 Cyclin D1 DDX17 DDX5 DNTTIP2 EP300 ESR2 FOXO1 GREB1 GTF2H1 ... "CDK-independent activation of estrogen receptor by cyclin D1". Cell. 88 (3): 405-15. doi:10.1016/S0092-8674(00)81879-6. hdl: ... also a D1-like receptor full agonist (R,R)-Tetrahydrochrysene ((R,R)-THC) - actually not selective over ERβ, but rather an ... a cyclin-dependent kinase-activating kinase complex ring finger factor, and regulates estrogen receptor transactivation ...
Cyclin D1, Cyclin-dependent kinase 7, DACH1, Death associated protein 6, L-DOPA, EFCAB6, Epidermal growth factor receptor, ... Reutens AT, Watanabe G, Albanese C, McPhaul MJ, Balk SP, Pestell RG (1998). "Cyclin D1 binds activating mutants of the androgen ... "Cyclin D1 binds the androgen receptor and regulates hormone-dependent signaling in a p300/CBP-associated factor (P/CAF)- ... "A central domain of cyclin D1 mediates nuclear receptor corepressor activity". Oncogene. 24 (3): 431-44. doi:10.1038/sj.onc. ...
Cyclin D1 and cancer development in laryngeal premalignancy patients. Cancer Prev Res (Phila) 2(1):14-21, 2009. Spitz MR, Hong ...
... can be associated with overexpression of the cyclin D1 gene. It is also associated with multiple endocrine ... Hsi ED, Zukerberg LR, Yang WI, Arnold A (May 1996). "Cyclin D1/PRAD1 expression in parathyroid adenomas: an immunohistochemical ...
Both MyoD and pRb are necessary for the repression of cyclin D1, but rather than acting directly on cyclin D1, they act on Fra- ... and thus cyclin D1) as either MyoD or pRb on its own is not sufficient alone to induce cyclin D1 repression and thus cell cycle ... This is done through regulation of the Cyclin, Cyclin D1. Cell cycle arrest (in which myoblasts would indicate the conclusion ... Zhang JM, Wei Q, Zhao X, Paterson BM (February 1999). "Coupling of the cell cycle and myogenesis through the cyclin D1- ...
Yano M, Naito Z, Yokoyama M, Shiraki Y, Ishiwata T, Inokuchi M, Asano G (Mar 1999). "Expression of hsp90 and cyclin D1 in human ... For example, the co-chaperone CDC37 (cell division cycle 37) stabilizes the cell cycle regulatory proteins CDK4 (cyclin ...
It, combined with the Ras pathway, downregulate cyclin D1, a cyclin-dependent kinase, if they are not stimulated by the ... In the presence of mitogens, sufficient cyclin D1 can be produced. This process cascades onwards, producing other cyclins which ... Smad proteins then trigger an increase in p15, which inhibits cyclin D1 and prevents cell cycle progression. In many cancers, ... and depends on cyclins to be passed. One of the most important of these is TP53, a gene which produces a family of proteins ...
Adnane J, Shao Z, Robbins PD (January 1999). "Cyclin D1 associates with the TBP-associated factor TAF(II)250 to regulate Sp1- ... Siegert JL, Rushton JJ, Sellers WR, Kaelin WG, Robbins PD (November 2000). "Cyclin D1 suppresses retinoblastoma protein- ...
Immunostains for smooth muscle actin and cyclin D1 are characteristically positive. The main histologic differential diagnosis ...
It reduces the growth of new cells by inhibiting cyclin D1. As a result, cells arrest during G1 phase and enter apoptosis. ... "Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin D1". J. Biol. Chem. 277 (19): 16464-9. doi: ...
Mantle cell lymphoma is excluded due to the lack of CD5 and cyclin-D1 expression. Clonal rearrangements of the immunoglobulin ... July 1998). "Absence of cyclin D1 protein expression in splenic marginal zone lymphoma". Mod. Pathol. 11 (7): 601-6. PMID ... November 1999). "Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q ...
Cyclin D1 overexpression supports stable EBV infection in nasopharyngeal epithelial cells. Proc.Natl.Acad.Sci.U.S.A 109, E3473- ...
... cyclin D1 is expressed but it may not be required. Cyclin D1 negative mantle cell lymphoma can be diagnosed by detecting SOX11 ... A defining characteristic of MCL is mutation and overexpression of cyclin D1, a cell cycle gene, that contributes to the ... MCL cells generally over-express cyclin D1 due to a t(11:14) chromosomal translocation in the DNA. Specifically, the ...
Lin HM, Zhao L, Cheng SY (August 2002). "Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors". J. Biol ... "A central domain of cyclin D1 mediates nuclear receptor corepressor activity". Oncogene. 24 (3): 431-44. doi:10.1038/sj.onc. ...
Cyclin-D1-binding protein 1 is a protein that in humans is encoded by the CCNDBP1 gene. This gene was identified by the ... CCNDBP1 has been shown to interact with GRAP2 and Cyclin D1. GRCh38: Ensembl release 89: ENSG00000166946 - Ensembl, May 2017 ... "Entrez Gene: CCNDBP1 cyclin D-type binding-protein 1". Xia, C; Bao Z; Tabassam F; Ma W; Qiu M; Hua S; Liu M (Jul 2000). "GCIP, ... Xia C, Bao Z, Tabassam F, Ma W, Qiu M, Hua S, Liu M (Aug 2000). "GCIP, a novel human grap2 and cyclin D interacting protein, ...
"Induction of cyclin D1 by simian virus 40 small tumor antigen". Proceedings of the National Academy of Sciences of the United ...
"Phosphorylation-dependent ubiquitination of cyclin D1 by the SCFFBX4-αBcrystallin complex". Mol. Cell. 24 (3): 355-66. doi: ...
... overexpression of FHL2 inhibit the proliferative activity of the HCC Hep3B cell line by decreasing its cyclin D1 expression and ... "Fos family members induce cell cycle entry by activating cyclin D1". Molecular and Cellular Biology. 18 (9): 5609-19. doi: ...
The lymphocytes have marker protein profiles (e.g. CD20 and Bcl-2 positive; CD5, cyclin D1 and CD10 negative) that are typical ... or cyclin D1 marker proteins along with some plasma cells and a variable number of reactive T-cells. Fifty percent of cases ... or cyclin D1. Some 6-19% of NMZL cases have been reported to be associated with autoimmune diseases such as rheumatoid ... marker proteins but do not express the cyclin D1 marker protein., the T-cell marker, CD10, or BCL6. There are various EMZL ...
Yoshihara T, Collado D, Hamaguchi M (2007). "Cyclin D1 down-regulation is essential for DBC2's tumor suppressor function". ...
Takahashi-Yanaga F, Sasaguri T (Apr 2008). "GSK-3beta regulates cyclin D1 expression: a new target for chemotherapy". Cellular ...
Diehl, JA; Yang, W; Rimerman, RA; Xiao, H; Emili, A (March 2003). "Hsc70 regulates accumulation of cyclin D1 and cyclin D1- ... For example, Hsc70 regulates the nuclear accumulation of cyclin D1, which is a key player in G1 to S phase cell cycle ...
"Estrogen regulation of cyclin E2 requires cyclin D1 but not c-Myc". Molecular and Cellular Biology. 29 (17): 4623-39. doi: ... "The chromatin remodeling factor CHD8 interacts with elongating RNA polymerase II and controls expression of the cyclin E2 gene ...
Maeda I, Ohta T, Koizumi H, Fukuda M (April 2001). "In vitro ubiquitination of cyclin D1 by ROC1-CUL1 and ROC1-CUL3". FEBS ... Singer JD, Gurian-West M, Clurman B, Roberts JM (September 1999). "Cullin-3 targets cyclin E for ubiquitination and controls S ... Singer JD, Gurian-West M, Clurman B, Roberts JM (September 1999). "Cullin-3 targets cyclin E for ubiquitination and controls S ... CUL3 has been shown to interact with: CAND1, Cyclin E1, DCUN1D1, KEAP1, and KLHL12. GRCh38: Ensembl release 89: ENSG00000036257 ...
Lin HM, Zhao L, Cheng SY (August 2002). "Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors". J. Biol ...
... activity and nuclear accumulation of cyclin D1-Cdk4 during G1". J. Biol. Chem. 273 (50): 33279-86. doi:10.1074/jbc.273.50.33279 ... cyclin-dependent protein serine/threonine kinase regulator activity. • protein binding. • ATP binding. • cyclin binding. • ... Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 ... 1993). "Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent ...
Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase ... cyclin binding. • cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine ... p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin- ... "Entrez Gene: CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1)".. *^ Gartel AL, Radhakrishnan SK (May 2005). "Lost in ...
Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... cyclin-dependent kinases, and other cell cycle proteins. The ... All these phases in the cell cycle are highly regulated by cyclins, ...
"CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle progression". Cell. 151 (6): 1308-18. doi ...
Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ...
... absence of regulator of G protein signalling 13 and differential expression of Cyclin D1 in mantle cell lymphoma". Leukemia. 17 ...
Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... "Activation of phospholipase D1 by Cdc42 requires the Rho insert ...
... , sold under the brand name Kisqali,[1] is an inhibitor of cyclin D1/CDK4 and CDK6, and is used for the treatment of ... Cyclin-dependent kinases (CDKs) 4 and 6 are enzymes that have been shown to promote cell division and multiplication in both ...
... has been shown to interact with DNM1,[7][8][9][10][11] Phospholipase D1,[12] CDK5R1,[13] PLD2,[12] CABIN1[14] and ... Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P (March 2001). "Amphiphysin 1 binds the cyclin-dependent kinase ... Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P (March 2001). "Amphiphysin 1 binds the cyclin-dependent kinase ...
細胞週期的進行是由不同的週期素(Cyclin)所調控。週期素意味著這些蛋白質的表現量會隨著細胞週期的進行而有所變化,進而確認週期素原來是扮演細胞週期調控的角色。依照目前的認知,就如同細胞週期G1期→S期→G2期→M期的進行,在G1期大量表現的週期素D( ... 兩類關鍵
... cyclin D1. The recruitment of TLS to the promoter of cyclin D1 is directed by long ncRNAs expressed at low levels and tethered ... Yik JH, Chen R, Nishimura R, Jennings JL, Link AJ, Zhou Q (October 2003). "Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA ... 44 (D1): D1161-D1166. doi:10.1093/nar/gkv1215. ISSN 0305-1048. PMC 4702861 . PMID 26578586. Kapranov P, Willingham AT, Gingeras ...
negative regulation of cyclin-dependent protein serine/threonine kinase activity. • lung development. • cytokine-mediated ...
Sustained D1 receptor activity is kept in check by Cyclin-dependent kinase 5. Dopamine receptor activation of Ca2+/calmodulin- ... D1 receptor agonism and D2 receptor blockade also increases mRNA translation by phosphorylating ribosomal protein s6, resulting ... Hummel M, Unterwald EM (2002). "D1 dopamine receptor: a putative neurochemical and behavioral link to cocaine action". J. Cell ... Williams GV, Castner SA (2006). "Under the curve: critical issues for elucidating D1 receptor function in working memory". ...
Siegert JL, Rushton JJ, Sellers WR, Kaelin WG, Robbins PD (November 2000). "Cyclin D1 suppresses retinoblastoma protein- ... One such example of E2F-regulated genes repressed by Rb are cyclin E and cyclin A. Both of these cyclins are able to bind to ... When E2F is free it activates factors like cyclins (e.g. cyclin E and cyclin A), which push the cell through the cell cycle by ... See also: cyclin-dependent kinase and DREAM complex. When it is time for a cell to enter S phase, complexes of cyclin-dependent ...
... this reduction in ERK also affects cyclin D1. The expression of the SHC proteins (all three) were also dramatically reduced ...
Both MyoD and pRb are necessary for the repression of cyclin D1, but rather than acting directly on cyclin D1, they act on Fra- ... and thus cyclin D1) as either MyoD or pRb on its own is not sufficient alone to induce cyclin D1 repression and thus cell cycle ... This is done through regulation of the Cyclin, Cyclin D1. Cell cycle arrest (in which myoblasts would indicate the conclusion ... "Coupling of the cell cycle and myogenesis through the cyclin D1-dependent interaction of MyoD with cdk4". EMBO J. 18 (4): 926- ...
CDKN2C, INK4C, p18, p18-INK4C, cyclin-dependent kinase inhibitor 2C, cyclin dependent kinase inhibitor 2C. ... CDKN2C‏ (Cyclin dependent kinase inhibitor 2C) هوَ بروتين يُشَفر بواسطة جين CDKN2C في الإنسان.[1][2][3] ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". مؤرشف من الأصل في 05 ديسمبر 2010.. الوسيط , ... negative regulation of cyclin-dependent protein serine/threonine kinase activity. • G1/S transition of mitotic cell cycle. • ...
"ARA54 is involved in transcriptional regulation of the cyclin D1 gene in human cancer cells". Carcinogenesis. 28 (8): 1752-8. ...
Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ...
As the amount of cyclin increases, more and more cyclin dependent kinases attach to cyclin signaling the cell further into ... A-1 - A-34; B-1; C-1; D-1; E-1 - E-2; F-1 - F-3; CR-1 - CR-6; G-1 - G-34; I-1 - I-48 (index)". The Quarterly Review of Biology ... At the peak of the cyclin attached to the cyclin dependent kinases this system pushes the cell out of interphase and into the M ... The control of each checkpoint is controlled by cyclin and cyclin-dependent kinases. The progression of interphase is the ...
"Initiation and termination of DNA replication during S phase in relation to cyclins D1, E and A, p21WAF1, Cdt1 and the p12 ... cyclin E, A (Cdk2,1) cyclin A, B, B3 (Cdk1) H. sapiens cyclin D 1,2,3 (Cdk4, Cdk6) cyclin E (Cdk2) cyclin A (Cdk2, Cdk1) cyclin ... Cyclin A / CDK2 - active in S phase.. *Cyclin D / CDK4, Cyclin D / CDK6, and Cyclin E / CDK2 - regulates transition from G1 to ... cyclin D (Cdk4) cyclin E (Cdk2) cyclin E, A (Cdk2,1) cyclin A, B, B3 (Cdk1) ...
CDK4/6 z cyklinami D1, D2 lub D3 oraz CDK2 inaktywują RB i promują przejście do fazy S. Z kolei CDK2 i CDK1 z odpowiednimi ... The cyclin-dependent kinase inhibitor SCH 727965 (dinacliclib) induces the apoptosis of osteosarcoma cells. „Mol Cancer Ther". ... cycliny D1, metaloproteinaz i c-MET[95]. Aktywacja TCF jest odpowiedzialna za hamowanie proapoptycznego syndekanu-2, który jest ...
Zhao L, Samuels T, Winckler S, Korgaonkar C, Tompkins V, Horne MC, Quelle DE (January 2003). "Cyclin G1 has growth inhibitory ... "The MDM2 C-terminal region binds to TAFII250 and is required for MDM2 regulation of the cyclin A promoter". The Journal of ...
de 2002). «Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4». Mol. Cell ... de 2001). «Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at functionally important serine and ... de 1997). «Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 complexes». Oncogene ( ... cyclins and cyclin dependent kinases». Oncogene (ENGLAND) 15 (2): 143-57. ISSN 0950-9232. PMID 9244350. doi:10.1038/sj.onc. ...
The first to be discovered was its capability to drive cell proliferation (upregulates cyclins, downregulates p21), but it also ... 15 D1,15 26.19 cM. Start. 61,985,391 bp[2]. End. 61,990,374 bp[2]. ...
Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... CDK8, K35, cyclin-dependent kinase 8, cyclin dependent kinase 8 ... Rickert P, Corden JL, Lees E (Jan 1999). "Cyclin C/CDK8 and cyclin H/CDK7/p36 are biochemically distinct CTD kinases". Oncogene ... The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate ... "Entrez Gene: CDK8 cyclin-dependent kinase 8".. *^ Nemet J, Jelicic B, Rubelj I, Sopta M (Feb 2014). "The two faces of Cdk8, a ...
2002). "Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin D1". J. Biol. Chem. 277 (19): 16464-9. ...
... cyclin D1 is translocated to the IgH promoter leading to cyclin D1 overexpression. Chromosomal translocation of the cyclin D1 ... Cyclin D1 is a protein that in humans is encoded by the CCND1 gene. The CCND1 gene encodes the cyclin D1 protein. The human ... Cyclin D1 is degraded via the CRL4-Ambra1 E3 at the end of the G1 phase. Phosphorylation of cyclin D1s threonine residue T286 ... Cyclin D1 and the mechanisms it regulates have the potential to be a therapeutic target for cancer drugs: Cyclin D1 has been ...
Although cyclin D1 had no effect on STAT3 DNA binding, cyclin D1 did bind to the transcriptional activation domain of STAT3, ... Bienvenu et al. have found that cyclin D1, independent of cyclin-dependent kinase 4 (Cdk4) activity, can inhibit STAT3-mediated ... Endogenous cyclin D1 associated with STAT3 in cells treated for 2 hours after treatment with interleukin 6 (IL-6), an activator ... F. Bienvenu, H. Gascan, O. Coqueret, Cyclin D1 represses STAT3 activation through a Cdk4-independent mechanism. J. Biol. Chem. ...
Cyclin D1 governs microRNA processing in breast cancer Cyclin D1 controls cell cycle progression and microRNA biogenesis ... regulates expression of cyclin D1. Furthermore, the group showed that many cancer patients encode a form of cyclin D1 that ... Cyclin D1 governs microRNA processing in breast cancer. Thomas Jefferson University. Journal. Nature Communications. Keywords. ... and colleagues developed transgenic mice that could induce cyclin D1 expression in the breast and examined cells with cyclin D1 ...
... encoding cyclin D1. Three clones, with cyclin D1 levels similar to those seen in colon cancer cell lines, were further ... In conclusion, cyclin D1 can act as an oncogene in vitro and in vivo, when produced in immortalized normal intestinal ... Oncogenic transformation of normal enterocytes by overexpression of cyclin D1.. Kazanov D1, Shapira I, Pick M, Kolker O, ... Cyclin D1 plays an important role in the multi-step process of gastrointestinal tumorigenesis. We hypothesize that normal ...
Expression of cyclin D1 correlates with malignancy in human ovarian tumours.. Barbieri F1, Cagnoli M, Ragni N, Pedullà F, ... Cyclin D1 is a cell cycle regulator of G1 progression that has been suggested to play a relevant role in the pathogenesis of ... The levels of cyclin D1 protein were undetectable in patients with benign disease, detectable in the majority of patients with ... Cyclin D1 protein and mRNA content were analysed by Western blotting and reverse transcriptase polymerase chain reaction ...
A team of researchers from Taiwan has linked the biomarker cyclin D1 with the level of aggressiveness of oral cancer, and ... This supports results from earlier studies that suggest that cyclin D1 could be used as a prognostic biomarker. ... More research is needed, but assessing levels of cyclin D1 at diagnosis could help to personalize treatment. ... and the results showed that increased levels of cyclin D1 were linked with later stage cancer and increased chance of the tumor ...
Cyclin D1 Down-Regulation, Cyclin-Dependent Kinase 4 Down-Regulation, P21 Activation, Phosphorylated Rb Down-Regulation ... 60 Abstracts with Cyclin D1 Down-Regulation Research. Filter by Study Type. Animal Study. ... Kahweol-mediated cyclin D1 degradation may contribute to the inhibition of the proliferation in human colorectal cancer cells. ... Pharmacological Actions : Antiproliferative , Apoptotic, Cell cycle arrest, Cyclin D1 Down-Regulation. Additional Keywords : ...
... no cyclin D2, and virtually no cyclin D3. As expected, the retinas of double-mutant cyclin D1−/−p27−/− mice lacked cyclin D1 ... namely D-cyclins and cyclin E. The D-cyclins (cyclins D1, D2, and D3) are expressed in an overlapping, redundant fashion in all ... Cyclin D1+/− mice (7, 8) were crossed with p27+/− (11) mice. The resulting cyclin D1+/−p27+/− heterozygotes were bred to ... Cyclin D1−/−p27−/− mice, derived from crossing cyclin D1+/−p27+/− heterozygotes, were born with the expected frequency. As ...
Rabbit polyclonal Cyclin D1 (phospho T286) antibody validated for WB, ELISA and tested in Human. Referenced in 1 publication. ... Anti-Cyclin D1 (phospho T286) antibody. See all Cyclin D1 primary antibodies. ... All lanes : Anti-Cyclin D1 (phospho T286) antibody (ab62151) at 1/500 dilution. Lane 1 : Extracts from Jurkat cells treated ... Evidence for cell cycle suppression and microRNA regulation of cyclin D1 during anoxia exposure in turtles.. Cell Cycle 11:1705 ...
Activation of the Cyclin D1 Promoter and Elevation of Cyclin D1 in Cells Transfected with β-Catenin.. We assessed the effect of ... Induction of cyclin D1 and β-catenin-responsive transactivation of the cyclin D1 promoter. (A) Cells from the 293T line were ... Identification of a LEF-1 Binding Sequence in the Cyclin D1 Promoter.. To identify the sequences in the cyclin D1 promoter that ... A recent study showed that cyclin D1 is a target for GSK-3β, which, by regulating cyclin D1 phosphorylation, may control the ...
... we observed that cyclin D1 protein and mRNA levels were reduced. Moreover, SNIP1 depletion results in inhibition of cyclin D1 ... SNIP1 itself is induced upon serum stimulation immediately prior to cyclin D1 expression. These effects were independent of the ... results define both a new function for SNIP1 and identify a previously unrecognized regulator of the cell cycle and cyclin D1 ... SNIP1 regulates cyclin D1 promoter activity. U-2 OS (a) and Saos-2 (b) cells were transfected with 1.5 μg of cyclin D1, cyclin ...
Cyclin D1 a protein that helps push a replicating cel... In addition to its role in regulating the cell cycle cyclin D1 induc ... Cyclin,D1,governs,microRNA,processing,in,breast,cancer,biological,biology news articles,biology news today,latest biology news, ... Cyclin D1 governs microRNA processing in breast cancer. ...(PHILADELPHIA) Cyclin D1 a protein that helps push a replicating cel ... regulates expression of cyclin D1. Furthermore, the group showed that many cancer patients encode a form of cyclin D1 that ...
The expression of cyclin D1 in mid-G1 phase is associated with sustained ERK activity, and we show here that Rho is required ... which results in a strikingly early G1-phase expression of cyclin D1. Thus, cyclin D1 is induced in mid-G1 phase because a Rho ... Timing of cyclin D1 expression within G1 phase is controlled by Rho Nat Cell Biol. 2001 Nov;3(11):950-7. doi: 10.1038/ncb1101- ... The expression of cyclin D1 in mid-G1 phase is associated with sustained ERK activity, and we show here that Rho is required ...
May act at least in part via inhibition of the cyclin-D1/CDK4 complex, thereby preventing phosphorylation of RB1 and blocking ... Cyclin-D1-binding protein 1Add BLAST. 359. Amino acid modifications. Feature key. Position(s). DescriptionActions. Graphical ... May act at least in part via inhibition of the cyclin-D1/CDK4 complex, thereby preventing phosphorylation of RB1 and blocking ... sp,O95273,CCDB1_HUMAN Cyclin-D1-binding protein 1 OS=Homo sapiens OX=9606 GN=CCNDBP1 PE=1 SV=2 ...
Rabbit recombinant monoclonal Cyclin D1 antibody [EPR2241] - C-terminal. Validated in WB, IP, IHC, ICC/IF and tested in Mouse, ... Anti-Cyclin D1 antibody [EPR2241] - BSA and Azide free (ab156448) *Anti-Cyclin D1 antibody [EPR2241] (Alexa Fluor® 488) ( ... Anti-Cyclin D1 antibody [EPR2241] (Alexa Fluor® 594) (ab203446) *Anti-Cyclin D1 antibody [EPR2241] (Alexa Fluor® 555) (ab203448 ... Lane 2 : Anti-Cyclin D1 antibody [EPR2241] - C-terminal (ab134175) at 2 µg/ml. Lane 1 : His-Tagged full-length human Cyclin D1 ...
Following extensive washing, Cyclin D1 Mouse Detection Antibody is added to detect the captured cyclin D1 protein. Anti-mouse ... PathScan® Total Cyclin D1 Sandwich ELISA Kit detects endogenous levels of cyclin D1 protein in human, monkey, mouse, and rat ... Total Cyclin D1 Sandwich ELISA Kit #7918. However, this kit has a low detection level for cyclin D1 in some cell lines, such as ... Total Cyclin D1 Sandwich ELISA Kit #7918. However, this kit has a low detection level for cyclin D1 in some cell lines, such as ...
... vergleichen Sie unsere Cyclin D1 Proteine von vielen Spezies. Finden Sie das richtige Produkt auf antikoerper-online.de. ... G1/S-specific cyclin-D1 b , cyclin D1 b , parathyroid adenomatosis 1 , G1/S-specific cyclin-D1 a , cyclin D1 a (PRAD1: ... Am meisten referenzierte Cyclin D1 Proteine. Show all Cyclin D1 Proteine (CCND1) with Pubmed References. * Human Cyclin D1 ... Weitere Proteine zu Cyclin D1 Interaktionspartnern. Human Cyclin D1 (CCND1) Interaktionspartner * Cyclin D1 is unsuitable for ...
The induction of cyclin D1 can also be mediated by a target of p53, the p21 (WAF1/CIP1) inhibitor of cyclin-dependent kinases. ... p53, through p21 (WAF1/CIP1), Induces Cyclin D1 Synthesis. Xinbin Chen, Jill Bargonetti and Carol Prives ... p53, through p21 (WAF1/CIP1), Induces Cyclin D1 Synthesis Message Subject (Your Name) has forwarded a page to you from Cancer ... The relationship between the induction of cyclin D1 and G1 arrest defines a new cellular response to p53. ...
Cyclin D1 expression is associated with poor prognostic features in estrogen receptor positive breast cancer ... whereas cyclin D1 in hormone receptor positive and low grade breast cancer. Experimental data has suggested that cyclin D1 and ... Cyclins D1 and E play an important role in breast carcinogenesis. High cyclin E expression is common in hormone receptor ... High cyclin D1 expression was associated with high grade (P , 0.0005), high cyclin A (P , 0.0005) and Ki67 (P , 0.0005) ...
Selected quality suppliers for anti-Cyclin D1 antibodies. ... Order monoclonal and polyclonal Cyclin D1 antibodies for many ... G1/S-specific cyclin-D1 b , cyclin D1 b , parathyroid adenomatosis 1 , G1/S-specific cyclin-D1 a , cyclin D1 a (PRAD1: ... Top referenced anti-Cyclin D1 Antibodies. Show all anti-Cyclin D1 (CCND1) Antibodies with Pubmed References. * Human Polyclonal ... Browse our anti-Cyclin D1 (CCND1) Antibodies. Full name:. anti-Cyclin D1 Antibodies (CCND1). On www.antibodies-online.com are ...
G1/S-specific cyclin-D1. A. 249. Homo sapiens. Mutation(s): 0 Gene Names: CCND1, BCL1, PRAD1. ... We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1 ... Cyclin-dependent kinase 4. B. 302. Homo sapiens. Mutation(s): 2 Gene Names: CDK4. EC: 2.7.11.22. ... Cyclin-dependent kinase inhibitor 1B. C. 72. Homo sapiens. Mutation(s): 0 Gene Names: CDKN1B, KIP1. ...
cyclin-D1-binding protein 1. Orthologs:. Homo sapiens (human) : CCNDBP1 (cyclin D1 binding protein 1) HGNC Alliance Mus ... Sus scrofa (pig) : CCNDBP1 (cyclin D1 binding protein 1) Chlorocebus sabaeus (green monkey) : CCNDBP1 (cyclin D1 binding ... cyclin D1 binding protein 1) Alliance Chinchilla lanigera (long-tailed chinchilla) : Ccndbp1 (cyclin D1 binding protein 1) Pan ... cyclin D1 binding protein 1) Ictidomys tridecemlineatus (thirteen-lined ground squirrel) : Ccndbp1 (cyclin D1 binding protein 1 ...
G1-Cyclin & Mantle Cell Marker. Validated: WB, ELISA, Flow, ICC/IF, IHC-Fr, IHC-P, IP, PAGE. Tested Reactivity: Human, Mouse, ... Cyclin D1 Antibody (DCS-6) [NBP2-15189] - analysis of Cyclin D1 in 1) C2C12, 2) HepG2, and 3) NIH3T3 lysate probed with Cyclin ... Cyclin D1 Antibody (DCS-6) Summary. Immunogen. Human recombinant full length Cyclin D1 protein was used as immunogen to ... The deregulation of cyclin D1 or other D types is commonly involved in a wide range of cancers. For example cyclin D1 is ...
... Br J Haematol. 1997 Oct; ... On the other hand, mature myeloma cells did not express cyclin D1 but expressed p16, not p21 or p27, as well as normal mature ... Immature myeloma cells as well as myeloma cell lines expressed cyclin D1 mRNA and protein, but not any Cdk inhibitors. ... Therefore these results show that immature myeloma cells constitutively express cyclin D1 and can proliferate, and mature ...
962 human cyclin D1 promoter CREB site mutant pGL3Basic from Dr. Frank McCormicks lab contains the insert CCND1 Promoter and ... 962 human cyclin D1 promoter CREB site mutant pGL3Basic (Plasmid #32732) Print ... Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Tetsu O, McCormick F. Nature. 1999 Apr 1;398(6726):422 ... Map Image for -962 human cyclin D1 promoter CREB site mutant pGL3Basic ...
NPFcyclin D1 cells (b), NPF alone (c), and NPFcyclin D1 alone (d). The graft volume of BPH-1 + NPFcyclin D1 was significantly ... BPH-1C7-cyclin D1, BPH-1C7-Δ, BPH-1NPF, NPFcyclin D1, and BPH-1NPF-cyclin D1 cells were generated as described below. All of ... and cyclin D1-overexpressing (BPH-1C7-cyclin D1) BPH-1 cell lines were generated by stable retroviral infection. Cyclin D1 ... A, gross morphology of 3-month grafts of BPH-1NPF (left) and BPH-1NPF-cyclin D1 (right). The volume of the BPH-1NPF-cyclin D1 ...
M. Abou EL-Ela, N. Nagui, D. Mahgoub, N. El-Eishi, M. Fawzy, A. El-Tawdy, R. Abdel Hay, L. Rashed, Expression of cyclin D1 and ... Cyclin D1, B and A expression and cell turnover in psoriatic skin lesions before and after cyclosporin treatment. Authors. *. C ... 2-3). Cyclin D1 was negative or expressed in a low percentage of nuclei in psoriasis before therapy (0·78), whereas it was ... Aim We evaluated epidermal cell turnover and thickness, as well as the expression of cyclins D1, B and A in psoriatic skin ...
Downloading a figure as powerpoint requires a browser with javascript support. Enable javascript and try again For help please contact [email protected] ...
G1-Cyclin & Mantle Cell Marker. Validated: IHC-P. Tested Reactivity: Human, Mouse, Rat, and more. 100% Guaranteed. ... Mouse Monoclonal Anti-Cyclin D1 Antibody (DCS-6) - IHC-Prediluted. ... Home » Cyclin D1 » Cyclin D1 Antibodies » Cyclin D1 Antibody (DCS-6) - IHC-Prediluted ... Cyclin D1 Antibody (DCS-6) - IHC-Prediluted Summary. Immunogen. Human recombinant full length Cyclin D1 protein was used as ...
... is a mouse monoclonal recommended for detecting cyclin D1 of mouse, rat and human origin by WB, IP, IF, IHC(P), FCM and ELISA ... Additional Cyclin Antibodies including cyclin A, cyclin A1, cyclin A2, cyclin B, cyclin B1, cyclin B2, cyclin B3, cyclin D2, ... cyclin D1 Antibody (DCS-6): sc-20044 cyclin D1 Antibody (DCS-6) is rated 4.2 out of 5 by 19. ... cyclin D1 Antibody (DCS-6) recommended for detection of cyclin D1 of mouse, rat and human origin by WB, IP, IF, IHC(P), FCM and ...
  • Cyclin D1 is a protein that in humans is encoded by the CCND1 gene. (wikipedia.org)
  • The CCND1 gene encodes the cyclin D1 protein. (wikipedia.org)
  • The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. (wikipedia.org)
  • Cyclin D1 is a protein required for progression through the G1 phase of the cell cycle. (wikipedia.org)
  • The cyclin D1-CDK4 complex promotes passage through the G1 phase by inhibiting the retinoblastoma protein (pRb). (wikipedia.org)
  • Phosphorylation of cyclin D1's threonine residue T286 marks the protein for binding to Ambra1, a substrate receptor of the CRL4 E3, which promotes cyclin D1 ubiquitylation and its subsequent degradation by the proteasome. (wikipedia.org)
  • The researchers noticed that cells lacking cyclin D1 produced less of the miRNA-processing protein, Dicer, and therefore had reduced levels of mature miRNA. (eurekalert.org)
  • Cyclin D1 protein and mRNA content were analysed by Western blotting and reverse transcriptase polymerase chain reaction respectively. (nih.gov)
  • Moreover, eight benign lesions, two borderline tumours and 11 carcinomas proved to be suitable for the analysis of cyclin D1 transcript, and emerging data demonstrated significant agreement between protein abundance and mRNA expression. (nih.gov)
  • Cyclin D1 protein levels were induced by β-catenin overexpression and reduced in cells overexpressing the cadherin cytoplasmic domain. (pnas.org)
  • Consistent with this result, we observed that cyclin D1 protein and mRNA levels were reduced. (nature.com)
  • PHILADELPHIA) Cyclin D1 a protein that helps push a replicating cel. (bio-medicine.org)
  • recombinant human Cyclin D 1 protein. (abcam.com)
  • Cyclin D1 protein from human (HT-1080 and MCF7), monkey (COS-7), mouse (C2C12), and rat (C6) cells was detected using PathScan ® Total Cyclin D1 Sandwich ELISA Kit #7918. (cellsignal.com)
  • The PathScan ® Total Cyclin D1 Sandwich ELISA Kit is a solid phase sandwich enzyme-linked immunosorbent assay (ELISA) that detects endogenous levels of total cyclin D1 protein. (cellsignal.com)
  • Following extensive washing, Cyclin D1 Mouse Detection Antibody is added to detect the captured cyclin D1 protein. (cellsignal.com)
  • The magnitude of absorbance for this developed color is proportional to the quantity of total cyclin D1 protein. (cellsignal.com)
  • Zusätzlich bieten wir Ihnen Cyclin D1 Antikörper (552) und Cyclin D1 Kits (62) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
  • This arrest is characterized by accumulation of the cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) and of underphosphorylated forms of retinoblastoma protein. (aacrjournals.org)
  • We show here that accumulation of the wild-type p53 protein in either human or murine cells markedly increases expression of cyclin D1. (aacrjournals.org)
  • Additionally we are shipping Cyclin D1 Kits (73) and Cyclin D1 Proteins (27) and many more products for this protein. (antibodies-online.com)
  • The p27 protein is a canonical negative regulator of cell proliferation and acts primarily by inhibiting cyclin-dependent kinases (CDKs). (rcsb.org)
  • Human recombinant full length Cyclin D1 protein was used as immunogen to generate this antibody. (novusbio.com)
  • Recognizes a protein of 36kDa, identified as cyclin D1. (novusbio.com)
  • Immature myeloma cells as well as myeloma cell lines expressed cyclin D1 mRNA and protein, but not any Cdk inhibitors. (nih.gov)
  • The cyclin D1 oncogene encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the Rb protein and promotes progression through G 1 to S phase of the cell cycle. (aacrjournals.org)
  • Several prostate cancer cell lines and a subset of primary prostate cancer samples have increased cyclin D1 protein expression. (aacrjournals.org)
  • Human prostate carcinoma cell lines frequently express elevated levels of cyclin D1 protein, although the gene is not amplified in these cells ( 18 ). (aacrjournals.org)
  • It is well established that the Cdc2 p34-cyclin B protein kinase plays a critical role in the G2 to M transition while cyclin A associates with Cdk2 p33 and functions in S phase. (scbt.com)
  • Cyclin D1 is frequently overexpressed in cancers and its overexpression can be attributed to many factors including increased transcription, translation, and protein stability. (pubmedcentralcanada.ca)
  • Cyclin D1 expression and accumulation are induced by growth factors and occur at multiple levels including increased transcription, translation, and protein stability. (pubmedcentralcanada.ca)
  • We constructed cyclin D1 and CDK4 protein interaction network in a human breast cancer cell line MCF7, and identified novel CDK4 protein partners. (sigmaaldrich.com)
  • We show that NGF represses over 6-8 d the levels of specific cdk kinase proteins and the G2-M phase specific cyclin B1 and the S phase marker PCNA as well as the level of phosphorylation of the retinoblastoma (Rb) protein. (jneurosci.org)
  • In agreement, NGF induced the cdk inhibitory protein, p21, which was found in cyclin D1/cdk kinase complexes after NGF treatment. (jneurosci.org)
  • The Cyclin D1- Cdk4/6 complex phosphorylates the Rb protein, leading to the release of E2F1, which then binds and activates other target genes, leading to G1-S transition of the cell cycle. (duke.edu)
  • We found that while TTP was not required for the PR-mediated decrease in Cyclin D1 mRNA stability, overexpression of this tumor suppressive protein was able to inhibit IL-1β-mediated stimulation of inflammatory genes in our breast cancer model. (duke.edu)
  • Cyclin D1 protein is overexpressed in hyperplasia and intraductal carcinoma of the breast. (aacrjournals.org)
  • Using immunohistochemistry, we examined cyclin D1 protein expression in 471 breast tissue samples. (aacrjournals.org)
  • This suggests that overexpression of cyclin D1 protein is important at the earliest stages of breast oncogenesis and continues to have a crucial role throughout the development of malignancy. (aacrjournals.org)
  • The finding that cyclin D1 is required for recruitment of G9a to target genes in chromatin and for H3K9 dimethylation, identifies a novel mechanism coordinating protein methylation. (jefferson.edu)
  • Regulation of cyclin D1 is responsive to native RASSF1A activity, because RNA interference-mediated downregulation of endogenous RASSF1A expression in human epithelial cells results in abnormal accumulation of cyclin D1 protein. (asm.org)
  • We reported previously that epidermal growth factor stimulation markedly increased cyclin D1 protein expression in human bronchial epithelial (HBE) cells, and this was opposed by chemoprevention with all- trans- retinoic acid. (aacrjournals.org)
  • The current study sought to determine whether the EGFR TKI erlotinib repressed cyclin D1 protein expression in immortalized HBE cells, lung cancer cell lines, and clinical aerodigestive tract cancers. (aacrjournals.org)
  • Non-small-cell lung cancer cell lines were also evaluated for changes in proliferation and cyclin protein expression after erlotinib treatments. (aacrjournals.org)
  • Erlotinib, at clinically achievable dosages, repressed BEAS-2B cell growth, triggered G 1 arrest, and preferentially reduced cyclin D1 protein expression and transcriptional activation. (aacrjournals.org)
  • Erlotinib also preferentially repressed proliferation and cyclin D1 protein expression in responsive, but not resistant, non-small-cell lung cancer cell lines. (aacrjournals.org)
  • Taken together, these in vitro and in vivo findings provide direct evidence for repression of cyclin D1 protein as a surrogate marker of response in aerodigestive tract cancers to erlotinib treatment. (aacrjournals.org)
  • The protein encoded by the Bcl-1 oncogene, known as cyclin D1, belongs to the highly conserved family of cyclin-dependent kinase (CDK) regulators. (clontech.com)
  • It is also known as CCND1, B-cell lymphoma 1 protein (BCL1), parathyroid adenomatosis 1 (PRAD1), B-cell CLL/lymphoma 1, G1/S-specific cyclin-D1, D11S287E, and U21B31. (clontech.com)
  • Cyclin D1 also interacts with tumor suppressor protein Rb. (clontech.com)
  • The antibodies were raised in mouse using a recombinant protein, and can be used for Western blot (WB) detection or immunohistochemical (IHC) detection of human cyclin D1 protein. (clontech.com)
  • The mouse monoclonal antibody DCS-6 recognizes cyclin D1, an ubiquitously expressed 33 kDa intracellular protein that migrates as a 36 kDa band under reducing SDS-PAGE conditions. (exbio.cz)
  • Background Mantle cell lymphoma is a clinically heterogeneous disease characterized by overexpression of cyclin D1 protein. (haematologica.org)
  • Simultaneous assessment of cyclin D1 and p16INK4A protein levels define subgroups of patients at increased risk of relapse and may be of clinical utility in optimizing therapy. (garvan.org.au)
  • Aims To investigate cyclin D1 and fascin immunoreactivity in normal, reactive and neoplastic vulvar skin correlating the findings with p16 protein and Ki67 expression. (bmj.com)
  • Methods 66 vulvar biopsy or resection specimens demonstrating normal appearances, reactive epidermal changes, usual-type vulvar intraepithelial neoplasia (uVIN), differentiated-type VIN (dVIN), p16-positive squamous cell carcinoma (SCC) and p16-negative SCC were examined immunohistochemically for cyclin D1, fascin, Ki67 and p16 protein. (bmj.com)
  • Mechanistic studies revealed that ETV4 directly regulates the expression of Cyclin D1 CCND1 , a protein crucial for cell-cycle progression from G 1 - to S-phase. (aacrjournals.org)
  • We show that this exit is preceded by p27-dependent inhibition of cyclin A-Cdk1/2, cyclin D1 downregulation and reduced pre-mitotic pRb pocket protein phosphorylation. (cnrs.fr)
  • ER subtype agonist based activation on A431 cells was performed to investigate their role in modulating mRNA and protein expression of tumor markers CD55 and Cyclin D1. (tu-dortmund.de)
  • Akt/cAMP-responsive element binding protein/cyclin D1 network: a novel target for prostate cancer inhibition in transgenic adenocarcinoma of mouse prostate model mediated by Nexrutine, a Phellodendron amurense bark extract. (semanticscholar.org)
  • Additionally, the report provides an overview of key players involved in G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1) targeted therapeutics development and features dormant and discontinued projects. (globalmarketsdirect.com)
  • The report analyses the pipeline products across relevant therapy areas under development targeting G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1). (globalmarketsdirect.com)
  • The report provides a snapshot of the Global therapeutic landscape for G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1). (globalmarketsdirect.com)
  • The report reviews G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1) targeted therapeutics under development by companies and universities/research institutes based on information derived from company and industry-specific sources. (globalmarketsdirect.com)
  • The report reviews key players involved in G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1) targeted therapeutics and enlists all their major and minor projects. (globalmarketsdirect.com)
  • The report assesses G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1) targeted therapeutics based on Mechanism of Action (MoA), Route of Administration (RoA) and Molecule Type. (globalmarketsdirect.com)
  • The report reviews latest news and deals related to G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1) targeted therapeutics. (globalmarketsdirect.com)
  • Identify and understand the targeted therapy areas and indications for G1/S Specific Cyclin D1 (B Cell Lymphoma 1 Protein or BCL 1 Oncogene or PRAD1 Oncogene or CCND1). (globalmarketsdirect.com)
  • Nuclei from SINE treated cells showed increased protein localization of XPO-1, survivin and cyclin D1 followed by degradation of these proteins leading to cell cycle arrest and apoptosis. (biomedcentral.com)
  • Using an activated allele of mitogen-activated protein kinase kinase 1 (MEK1), we show that this kinase plays a significant role in positively regulating the expression of cyclin D1. (elsevier.com)
  • Feeding WD to Apc(1638N/+) mice not only enhanced cyclin D1 expression in colonic epithelium compared with AIN-76A treatment as previously reported but also significantly increased the expression of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) concomitantly with a decrease in the proapoptotic Bcl2-associated X protein and the number of apoptotic epithelial cells. (pubfacts.com)
  • Phosphorylation of JunB by the p34 cdc2 -cyclin B kinase is associated with lower JunB protein levels in mitotic and early G 1 cells. (embopress.org)
  • Specific cyclin-cdk complexes affect transcription through phosphorylation of components of the basal transcription apparatus (RNA polymerases and basal transcription factors), transcriptional modulators such as the retinoblastoma protein Rb, and transcription factors. (embopress.org)
  • The best studied example of the regulation of transcription factors by the cell cycle machinery is the modulation of the E2F protein family activity by cyclin-cdk complexes. (embopress.org)
  • Furthermore, the correlation between the mRNA/protein and GCA clinical pathologic parameters were analyzed, and the ralationship of p57 kip2 and cyclinD1 in GCA were also evaluated. (oncotarget.com)
  • The protein expression of p57 kip2 was not correlated to the protein expression of cyclinD1 ( P = 0.55). (oncotarget.com)
  • Cyclin D1 is a key mediator of cell cycle progression in hepatocytes, and transient expression of this protein is sufficient to promote robust proliferation of these cells in vivo. (lu.se)
  • Cyclin D1 is involved in cell cycle transition and has been shown to interact with the retinoblastoma protein. (bio-rad-antibodies.com)
  • Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. (bosterbio.com)
  • The gain of cytosolic DEDD enhances cyclin D1 expression by interacting with heat shock 71 kDa protein 8 (HSC70). (nature.com)
  • Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. (wikipedia.org)
  • By definition, a CDK binds a regulatory protein called a cyclin. (wikipedia.org)
  • Cyclins function as regulators of CDKs (Cyclin-dependent kinase). (wikipedia.org)
  • have found that cyclin D1, independent of cyclin-dependent kinase 4 (Cdk4) activity, can inhibit STAT3-mediated signaling. (sciencemag.org)
  • These proteins are believed to drive cell cycle progression by associating with their kinase partners, cyclin-dependent kinases, and by directing phosphorylation of critical cellular substrates. (pnas.org)
  • In addition, D-cyclins play a kinase-independent role by sequestering cell cycle inhibitors p27 Kip1 and p21 Cip1 . (pnas.org)
  • More recent work indicates that the induction of cyclin D-CDK complexes results in the redistribution of CDK inhibitor p27 Kip1 from cyclin E-CDK2 complexes to cyclin D-CDK4/6 complexes, thereby triggering the kinase activity of cyclin E-CDK2 holoenzyme ( 6 ). (pnas.org)
  • Thus, D-cyclins also control cell cycle progression in a kinase-independent manner, via their interaction with p27 Kip1 . (pnas.org)
  • In order to further clarify the biological differences between these immature and mature myeloma cells, we examined survival of these cells with or without IL-6 in vitro, and investigated the underlying mechanism of the proliferative or non-proliferative character of these cells by examining expression of cell cycle regulators such as cyclin D1 and inhibitors for cyclin-dependent kinase (Cdk), p16INK4A, p21CIP1 and p27KIP1 by RT-PCR and immunohistochemistry. (nih.gov)
  • It is known that the cell cycle and cell proliferation are regulated by the sequential activation of cyclin-dependent kinase/cyclin complexes. (wiley.com)
  • While our fundamental understanding of the normal physiological functions of the cyclin-dependent kinase has increased dramatically, the potential pathological functions/activities remain to be established. (pubmedcentralcanada.ca)
  • Recent efforts have provided insights into the precise mechanisms whereby the cyclin D1-dependent kinase promotes tumorigenic growth and are discussed below. (pubmedcentralcanada.ca)
  • Although the levels of cyclin D1/cdk2 and cyclin D1/cdk4 complexes increased following NGF treatment, as did cyclin D1/Rb complexes, the associated kinase activities declined, indicating that NGF also induces an inhibitor of cdk kinase activity. (jneurosci.org)
  • Takano Y, Takenaka H, Kato Y, Masuda M, Mikami T, Saegusa M, Okayasu I. Cyclin D1 overexpression in invasive breast cancers: correlation with cyclin-dependent kinase 4 and oestrogen receptor overexpression, and lack of correlation with mitotic activity. (acronymattic.com)
  • CCND1 (cyclin D1), a key regulator of the mammalian G 1 -S-phase transition, is phosphorylated on Thr 286 by GSK3β (glycogen synthase kinase 3β) to promote its degradation. (portlandpress.com)
  • Diehl JA, Cheng M, Roussel MF, Sherr CJ: Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. (exbio.cz)
  • Yang W, Zhang Y, Li Y, Wu Z, Zhu D: Myostatin induces cyclin D1 degradation to cause cell cycle arrest through a phosphatidylinositol 3-kinase/AKT/GSK-3 beta pathway and is antagonized by insulin-like growth factor 1. (exbio.cz)
  • Cyclin D1-dependent kinase phosphorylates NRF-1 at S47. (jefferson.edu)
  • Cyclin D1 destabilization involved its phosphorylation by GSK-3beta at threonine-286 since overexpression of the kinase-dead mutant of GSK-3beta or cyclin D1T286A mutant conferred stability to cyclin D1. (aacrjournals.org)
  • We report here the crucial role of cyclin D1 in promoting this effect in a cyclin-dependent kinase (CDK)4/6-independent manner in multiple myeloma (MM) cells. (archives-ouvertes.fr)
  • The synthesis of cyclin D1 and its assembly with cyclin-dependent kinase 4 (CDK4) to form an active complex is a rate-limiting step in progression through the G 1 phase of the cell cycle. (elsevier.com)
  • abstract = "The synthesis of cyclin D1 and its assembly with cyclin-dependent kinase 4 (CDK4) to form an active complex is a rate-limiting step in progression through the G1 phase of the cell cycle. (elsevier.com)
  • Moreover, some but not all E2F proteins are direct substrates of specific cyclin-cdk kinase complexes and phosphorylation affects their binding to DNA. (embopress.org)
  • only the cyclin-CDK complex is an active kinase but its activity can be typically further modulated by phosphorylation and other binding proteins, like p27. (wikipedia.org)
  • Amplification of the CCND1 gene is present in: non-small cell lung cancers (30-46%) head and neck squamous cell carcinomas (30-50%) pancreatic carcinomas (25%) bladder cancer (15%) pituitary adenomas (49-54%) breast carcinoma (13%) Cyclin D1 overexpression is strongly correlated to ER+ breast cancer and deregulation of cyclin D1 is associated with hormone therapy resistance in breast cancer. (wikipedia.org)
  • The nontumorigenic intestinal epithelial cell line, IEC-18, was transfected with the vector pMV7-CCND1, encoding cyclin D1. (nih.gov)
  • Background: Cyclin D1 gene (CCND1) plays pivotal roles in the development of several human cancers, including breast cancer, functioning as an oncogene. (hindawi.com)
  • Auf www.antikoerper-online.de finden Sie aktuell 24 Cyclin D1 (CCND1) Proteine von 9 unterschiedlichen Herstellern. (antikoerper-online.de)
  • On www.antibodies-online.com are 609 Cyclin D1 (CCND1) Antibodies from 40 different suppliers available. (antibodies-online.com)
  • The t(11;14) translocation that juxtaposes the Cyclin D1 ( CCND1 ) gene to the immunoglobulin heavy chain gene is considered a hallmark of mantel cell lymphoma (MCL). (haematologica.org)
  • Staining for Cyclin D1 (CCND1) revealed internal positive controls (macrophages and endothelial cells) but no staining of lymphoma cells (G). Fluorescence in situ hybridization using a break apart probe shows that the CCND1 gene of patient A has a chromosomal rearrangement (H). A cell nucleus where the segregation of the two fluorescent probes (red and green) is clearly visible is indicated by two arrows. (haematologica.org)
  • Mouse IgG monoclonal antibody for Cyclin D1, cyclin D1 (CCND1) detection. (bosterbio.com)
  • The absorbance readings at 450 nm are shown in the top figure, while the corresponding western blot using Cyclin D1 Antibody #2922, is shown in the bottom figure. (cellsignal.com)
  • A Cyclin D1 Rabbit Antibody has been coated onto the microwells. (cellsignal.com)
  • After incubation with cell lysates, both phospho and nonphospho cyclin D1 proteins are captured by the coated antibody. (cellsignal.com)
  • Western Blot: Cyclin D1 Antibody (DCS-6) [NBP2-15189] - Human uterine mesodermal tumor cell extract was separated on SDS-PAGE and probed with Monoclonal AB to Cyclin D1 (DCS-6). (novusbio.com)
  • Immunohistochemistry-Paraffin: Cyclin D1 Antibody (DCS-6) [NBP2-15189] - Formalin-paraffin human mantle cell lymphoma stained with Cyclin D1 Ab (Clone DCS-6). (novusbio.com)
  • Flow Cytometry: Cyclin D1 Antibody (DCS-6) [NBP2-15189] - Analysis using Alexa Fluor (R) 647 conjugate of NBP2-15189. (novusbio.com)
  • Cyclin D1 staining of HCT116 cells using Alexa Fluor 647 conjugated Cyclin D1 antibody. (novusbio.com)
  • This antibody neutralizes the activity of cyclin D1 in vivo. (novusbio.com)
  • This antibody is useful in identifying mantle cell lymphomas (cyclin D1 positive) from CLL/SLL and follicular lymphomas (cyclin D1 negative). (novusbio.com)
  • There are currently no images for Cyclin D1 Antibody (NBP2-44584). (novusbio.com)
  • Is there any possibility to obtain the cytometric protocol that displayed these results?For WB this antibody is very clear, but by Flow cytometry there is no difference in signal fro cyclin D1 negat/pos cells. (scbt.com)
  • WB result of Cyclin D1 antibody (60186-1-Ig, 1:12,000) with si-Control and si-Cyclin D1 transfected HeLa cells. (cosmobio.co.jp)
  • Flow cytometry intracellular staining pattern of HUVEC cells stained using anti-Cyclin D1 (DCS-6) PE antibody (concentration in sample 15 μg/ml). (exbio.cz)
  • Separation of HUVEC cells stained using anti-Cyclin D1 (DCS-6) PE antibody (concentration in sample 15 μg/ml, red-filled) from HUVEC cells stained using mouse IgG2a isotype control (MOPC-173) PE antibody (concentration in sample 15 μg/ml, black-dashed) in flow cytometry analysis (intracellular staining) of HUVEC cell suspension. (exbio.cz)
  • Cyclin D1+D2 antibody LS-C525346 is a biotin-conjugated mouse monoclonal antibody to Cyclin D1+D2 from human. (lsbio.com)
  • Rabbit anti cyclin D1 antibody recognizes Cyclin D1, a member of the cyclin family that function as CKD reculators. (bio-rad-antibodies.com)
  • In conclusion, cyclin D1 can act as an oncogene in vitro and in vivo, when produced in immortalized normal intestinal epithelial cells. (nih.gov)
  • Cyclin D1 is an oncogene frequently overexpressed in human cancers that has a dual function as cell cycle and transcriptional regulator, although the latter is widely unexplored. (jci.org)
  • Cyclin D1, one of the key cell cycle regulators, is a putative proto-oncogene overexpressed in a wide variety of human neoplasms. (novusbio.com)
  • Considerable effort directed towards the identification of G1 cyclins has led to the isolation of cyclin D, cyclin C and cyclin E. Of these, cyclin D corresponds to a putative human oncogene, designated PRAD1, which maps at the site of the Bcl1 rearrangement in certain lymphomas and leukemias. (scbt.com)
  • An integrative analysis of the extended cyclin D1 cancer interactome and somatic copy number alterations in human cancers identified BAIAPL21 as a potential novel human oncogene. (sigmaaldrich.com)
  • The cell cycle regulatory gene cyclin D1 is a candidate oncogene in breast cancer. (aacrjournals.org)
  • Targeted deletion of the gene encoding cyclin D1 demonstrates an essential role in normal mammary gland development while transgenic studies provide evidence that cyclin D1 is a weak oncogene in mammary epithelium. (garvan.org.au)
  • Cyclin D1 proto-oncogene is an important regulator of G1 to S phase progression in many different cell types. (alliedacademies.org)
  • The cyclin D1 gene is overexpressed in human breast cancers and is required for oncogene-induced tumorigenesis. (elsevier.com)
  • Cyclin D1-CDK4 inhibits pRb through phosphorylation, allowing E2F transcription factors to transcribe genes required for entry into the S phase. (wikipedia.org)
  • Synthetic phosphopeptide derived from human Cyclin D1 around the phosphorylation site of threonine 286 (A-C-T P -P-T). (abcam.com)
  • May act at least in part via inhibition of the cyclin-D1/CDK4 complex, thereby preventing phosphorylation of RB1 and blocking E2F-dependent transcription. (uniprot.org)
  • Evidence has established that members of the cyclin D family function to regulate phosphorylation of the retinoblastoma gene product, thereby activating E2F transcription factors. (scbt.com)
  • Early work resulted in the identification of the individual cyclin-dependent kinases that are activated during distinct cell cycle phases and contributed to our understanding of how phosphorylation of downstream targets in turn contributes to regulated cell cycle transitions. (pubmedcentralcanada.ca)
  • Diehl JA, Zindy F, Sherr CJ: Inhibition of cyclin D1 phosphorylation on threonine-286 prevents its rapid degradation via the ubiquitin-proteasome pathway. (exbio.cz)
  • Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. (jefferson.edu)
  • Cyclin D1 level changes are partially controlled by GSK-3β-dependent phosphorylation at threonine-286 (Thr286), which targets cyclin D1 for ubiquitination and proteolytic degradation. (oup.com)
  • Immunoblot analyses revealed a significant decrease in phosphorylation of retinoblastoma Rb and cyclin D1 in shRNA25 compared with shRNA08. (oup.com)
  • An increase in AKT activity was also observed in shRNA25, supported by a ∼1.5-fold elevation in phosphorylation and ∼50% reduction/deactivation of GSK-3α/β at Ser21/9, which were accompanied by a decrease in phosphorylation of cyclin D1 at T286. (oup.com)
  • Repression of E2F transactivation through binding to the Rb family of pocket proteins is relieved by cyclin-cdk‐mediated pRb phosphorylation. (embopress.org)
  • The four major mechanisms of CDK regulation are cyclin binding, CAK phosphorylation, regulatory inhibitory phosphorylation, and binding of CDK inhibitory subunits (CKIs). (wikipedia.org)
  • In mammalian cells, the activating phosphorylation occurs after cyclin binding. (wikipedia.org)
  • Studies have shown that mouse prostatic normal and Rb −/− epithelial cells have elevated cyclin D1 expression as they enter the cell cycle ( 18 ). (aacrjournals.org)
  • In prior work, they showed that cyclin D1 regulates the non coding genome, and that the non-coding genome, in turn, regulates expression of cyclin D1. (eurekalert.org)
  • Expression of cyclin D1 correlates with malignancy in human ovarian tumours. (nih.gov)
  • In the current study, the expression of cyclin D1 has been investigated in a series of 33 patients, with benign (10 patients), borderline (five patients) and malignant (18 patients) ovarian disease. (nih.gov)
  • Although the cyclin D1 gene is not amplified in human colon cancer, the expression of cyclin D1 is elevated in about 30% of human adenocarcinomas and in adenomatous polyps of the colon ( 28 , 29 ), and expression of anti-sense cyclin D1 cDNA abolished the growth of SW480 colon cancer cells in nude mice, indicating a critical role for cyclin D1 in tumorigenesis ( 30 ). (pnas.org)
  • The expression of cyclin D1 in mid-G1 phase is associated with sustained ERK activity, and we show here that Rho is required for the sustained ERK signal. (nih.gov)
  • However, we also report that Rho inhibits an alternative Rac/Cdc42-dependent pathway, which results in a strikingly early G1-phase expression of cyclin D1. (nih.gov)
  • q32) translocation resulting in over-expression of cyclin D1. (novusbio.com)
  • We show that vector over expression of cyclin D1 in PC12 is sufficient on its own to arrest the cells in G1 phase and inhibit expression of PCNA. (jneurosci.org)
  • RASSF1A inhibits accumulation of native cyclin D1, and the RASSF1A-induced cell cycle arrest can be relieved by ectopic expression of cyclin D1 or of other downstream activators of the G 1 /S-phase transition (cyclin A and E7). (asm.org)
  • Expression of cyclin D1 is required for cancer cell survival and proliferation. (biologists.org)
  • Therefore, expression of cyclin D1 prevents cancer cells from undergoing senescence, at least partially, by keeping the level of intracellular oxidative stress at a tolerable sub-lethal level. (biologists.org)
  • No expression of Cyclin D1 was observed in either ADH or UDH. (eurekamag.com)
  • These effects on the growth and cell cycle were reversed by the forced expression of Cyclin D1 in ETV4-silenced pancreatic cancer cells. (aacrjournals.org)
  • The aims of this study were to examine the immunohistochemical expression of Cyclin D1 in prostatic carcinoma and to demonstrate the association or relation between Cyclin D1 expressions and to determine the aggressiveness of the malignant tumors by Gleason Score. (alliedacademies.org)
  • Aberrant expression of cyclin D1, frequently observed in human malignant disorders, has been linked to the control of G 1 →S cell cycle phase transition and development and progression in carcinogenesis. (oup.com)
  • A single topical application of OTA (100 nmol/mouse) caused significant enhancement in short-term markers of skin tumor promotion such as ornithine decarboxylase activity, DNA synthesis, hyperplasia as well as expression of cyclin-D1 and COX-2 in mouse skin. (oup.com)
  • Adipocyte differentiation by PPARγ-specific ligands (BRL49653, troglitazone) was enhanced in cyclin D1 -/- fibroblasts and reversed by retroviral expression of cyclin D1. (elsevier.com)
  • Increased expression of cyclin D1 and amplification of its gene along with immunolabelling of HBME-1 in WDT-UMP lesions showing cytological features of papillary thyroid carcinoma within follicular adenomatoid nodules suggest that these areas could correspond to a precursor lesion of follicular variant of PTC. (biomedcentral.com)
  • Cyclin D1 was originally cloned as a breakpoint rearrangement in parathyroid adenoma and was shown to be required for progression through the G1 phase of the cell cycle to induce cell migration, angiogenesis and to induce the Warburg effect. (wikipedia.org)
  • Cyclin D1 overexpression has been shown to correlate with early cancer onset and tumor progression and it can lead to oncogenesis by increasing anchorage-independent growth and angiogenesis via VEGF production. (wikipedia.org)
  • The work supports the idea that cancer-causing proteins like cyclin D1 may drive cancer progression in part via miRNA biogenesis. (eurekalert.org)
  • Cyclin D1 is a cell cycle regulator of G1 progression that has been suggested to play a relevant role in the pathogenesis of several human cancer types. (nih.gov)
  • The progression of mammalian cells through the G 1 phase of the cell cycle is governed by two classes of cyclins, namely D-cyclins and cyclin E. The D-cyclins (cyclins D1, D2, and D3) are expressed in an overlapping, redundant fashion in all proliferating cell types. (pnas.org)
  • D-cyclins are thought to drive cell cycle progression by associating with their catalytic partners (termed cyclin-dependent kinases CDK4 and CDK6) and by guiding these kinases to their cellular substrates ( 1 ). (pnas.org)
  • Increased β-catenin levels may thus promote neoplastic conversion by triggering cyclin D1 gene expression and, consequently, uncontrolled progression into the cell cycle. (pnas.org)
  • Cyclin D1 is a major regulator of the progression of cells into the proliferative stage of the cell cycle ( 27 ). (pnas.org)
  • Unscheduled activation of cyclin D1 transcription by the β-catenin/LEF-1 complex in colon cancer cells may result in uncontrolled cell proliferation and thus contribute to tumor progression in these cells. (pnas.org)
  • Our results show that Rho is crucial for maintaining the correct timing of cyclin D1 expression in G1 phase and describe a new role for cytoskeletal integrity in the regulation of cell cycle progression. (nih.gov)
  • However, the relationship between cyclin D1 expression and prostate tumor progression has yet to be clearly characterized. (aacrjournals.org)
  • D-type cyclins (D1, D2, and D3) are G1-specific cyclins that associate with CDK4 or CDK6, and promote restriction point progression during G1 phase ( Sherr, 1993 ). (pubmedcentralcanada.ca)
  • Unlike other cyclins that are periodically synthesized during cell cycle progression, expression and accumulation of D-cyclins are strongly dependent on extracellular mitogenic cues. (pubmedcentralcanada.ca)
  • The increase in cyclin D1 expression in the overall progression from NBE to IC was also highly significant (P = 0.0001). (aacrjournals.org)
  • Therefore, cyclin D1 expression was detected at levels significantly greater than in NBE in the earliest proliferative epithelial lesions of the breast with a further significant increase accompanying the progression to any form of cancer. (aacrjournals.org)
  • The cyclin D1 gene product encodes the regulatory subunit of the holoenzyme that phosphorylates pRB and NRF1 thereby governing cell-cycle progression and mitochondrial metabolism. (jefferson.edu)
  • Rare alleles of RASSF1A, isolated from tumor cell lines, encode proteins that fail to block cyclin D1 accumulation and cell cycle progression. (asm.org)
  • Hyperphosphorylation of Rb by cyclin D-CDK4 and cyclin E-CDK2 complexes is permissive for progression of proliferating cells into S phase. (asm.org)
  • Using diploid fibroblasts, we demonstrate that NF-κB is required to induce cyclin D1 expression and pRb hyperphosphorylation and promote G 1 -to-S progression. (asm.org)
  • In conclusion, our findings indicate that the circMYLK/miR-195/cyclin D1 regulatory axis could affect the proliferation and cell cycle progression of LSCC cells, and may provide a novel therapeutic target for the treatment of LSCC. (portlandpress.com)
  • Albrecht JH, Hansen LK: Cyclin D1 promotes mitogen-independent cell cycle progression in hepatocytes. (exbio.cz)
  • The cell cycle regulatory gene, Cyclin D1, plays a critical role in the growth and progression of several types of human cancer, including breast cancer. (eurekamag.com)
  • Moreover, to clarify whether Cyclin D1 expression is involved in multistep carcinogenesis or the progression of human breast cancer, we immunohistochemically investigated Cyclin D1 expression in 57 DCIS, 10 atypical ductal hyperplasia (ADH), 70 usual ductal hyperplasia (UDH), 44 PIC and 92 IDC. (eurekamag.com)
  • Since JunB represses and c‐Jun activates the cyclin D1 promoter, these modifications of AP‐1 activity during the M-G 1 transition could provide an impetus for G 1 progression by a temporal increase in cyclin D1 transcription. (embopress.org)
  • While experiments in different organisms have helped to dissect the post‐transcriptional mechanisms by which cell cycle proteins are regulated, less is known about the mechanisms that regulate cyclin gene transcription during cell cycle progression. (embopress.org)
  • On the contrary, cyclinD1 is a positive regulator of cell cycle progression. (oncotarget.com)
  • Conclusion: The expression of p57 kip2 and cyclinD1 are likely to suppress or promote the tumorigenesis and progression of GCA. (oncotarget.com)
  • In cdk2 -/- mice and animals treated with the cdk2 inhibitor seliciclib, cyclin D1 failed to induce hepatocyte cell cycle progression. (lu.se)
  • Most of the known cyclin-CDK complexes regulate the progression through the cell cycle. (wikipedia.org)
  • Cyclin D1-CDK4 also associates with several transcription factors and transcriptional co-regulators. (wikipedia.org)
  • Although cyclin D1 had no effect on STAT3 DNA binding, cyclin D1 did bind to the transcriptional activation domain of STAT3, suggesting a mechanism whereby STAT3-dependent transcription could be immediately attenuated. (sciencemag.org)
  • Here, we investigated the transcriptional role of cyclin D1 in lymphoid tumor cells with cyclin D1 oncogenic overexpression. (jci.org)
  • Cyclin D1 showed widespread binding to the promoters of most actively transcribed genes, and the promoter occupancy positively correlated with the transcriptional output of targeted genes. (jci.org)
  • Despite this association, the overexpression of cyclin D1 in lymphoid cells led to a global transcriptional downmodulation that was proportional to cyclin D1 levels. (jci.org)
  • This cyclin D1-dependent global transcriptional downregulation was associated with a reduced nascent transcription and an accumulation of promoter-proximal paused RNA polymerase II (Pol II) that colocalized with cyclin D1. (jci.org)
  • This transcriptional impairment seems to be mediated by the interaction of cyclin D1 with the transcription machinery. (jci.org)
  • This finding of global transcriptional dysregulation expands the known functions of oncogenic cyclin D1 and suggests the therapeutic potential of targeting the transcriptional machinery in cyclin D1-overexpressing tumors. (jci.org)
  • We further show that transcriptional activation of the cyclin D1 gene in such cells can be inhibited by enhancing the degradation of β-catenin with wild-type APC and axin or by its binding to the cadherin cytoplasmic tail. (pnas.org)
  • Unexpectedly, we found that contrary to what has been published before, the induction of Cyclin D1 mRNA expression was a primary transcriptional event and we have demonstrated the specific interaction of PR with PREs (progesterone response elements) located on this gene. (duke.edu)
  • NF-κB regulation of cyclin D1 occurs at the transcriptional level and is mediated by direct binding of NF-κB to multiple sites in the cyclin D1 promoter. (asm.org)
  • These data therefore identify cyclin D1 as an important transcriptional target of NF-κB and reveal a mechanism to explain how NF-κB is involved in the early phases of the cell cycle to regulate cell growth and differentiation. (asm.org)
  • Furthermore, genetic inactivation of the β-catenin transcriptional target, cyclin D1, impairs expansion of the skeletogenic precursors contributing to deficiencies in calvarial ossification. (biomedcentral.com)
  • Cyclin D1 is a regulatory subunit of cyclin-dependent kinases CDK4 and CDK6. (wikipedia.org)
  • The induction of cyclin D1 can also be mediated by a target of p53, the p21 (WAF1/CIP1) inhibitor of cyclin-dependent kinases. (aacrjournals.org)
  • We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1). (rcsb.org)
  • Cyclins function as allosteric regulatory subunits for the cyclin-dependent kinases (CDKs). (pubmedcentralcanada.ca)
  • These results indicate that NGF induction of cyclin D1 and inactivation of cdk kinases, the latter possibly by increase of p21, play a central role in the NGF block of PC12 cell cycling. (jneurosci.org)
  • Stimulation by growth factors induces the transcription of Cyclin D1 which in turn activates the cyclin dependent kinases (CDKs). (duke.edu)
  • In eukaryotic cells, these include the different cyclins, cyclin‐dependent kinases (cdks) and their inhibitors. (embopress.org)
  • Cyclins function as regulators of CDK kinases. (abclonal.com)
  • Using antisense RNA, Dr. Pestell's group was the first to show that cyclin D1 drives mammary tumor growth in vivo. (eurekalert.org)
  • The study involved cancer samples from 264 Taiwanese male oral cavity squamous cell carcinoma (OSCC) patients, and the results showed that increased levels of cyclin D1 were linked with later stage cancer and increased chance of the tumor spreading, as well as a reduced chance of survival. (fiercebiotech.com)
  • These data indicated that the tumor-promoting activity of cyclin D1 may be tissue specific. (aacrjournals.org)
  • Lastly, we derived an Aggregate Expression Score (AES), which quantifies the expression of all cyclin D1 interactors in a given tumor. (sigmaaldrich.com)
  • Overexpression of cyclin D1 occurred in 68% of tumors (100 of 147) and was associated with increased lymph node stage (P = 0.014), increased tumor grade (P = 0.003), and reduced disease-free (P = 0.006) and overall (P = 0.01) survival. (garvan.org.au)
  • We found high-frequency expression of MAGE-A9 and NY-ESO-1 in 36% and 55% of samples, respectively, and overexpression of PRAME, RAGE-1, CA-IX, Cyclin D1, ADFP, C-MET, and RGS-5 in many of the tumor samples. (uzh.ch)
  • Cyclin D1-specific CD8+ T cells secreted TNF-α, IFN-γ, and interleukin-2 (IL-2), and degranulated, indicating the presence of polyfunctional tumor-specific CD8+ T cells in the blood of these patients with ccRCC. (uzh.ch)
  • TCF1 knockdown in PyMT tumor cells suppressed Wnt signaling and mammosphere formation, which was due to Cyclin D1 attenuation. (aacrjournals.org)
  • The aim of this study was to describe the clinical features and expression of bcl-2, cyclin D1, p53, and proliferating cell nuclear antigen (PCNA) antibodies in syndromic (nevoid basal cell carcinoma syndrome [NBCCS]) and nonsyndromic patients diagnosed with keratocystic odontogenic tumor (KCOT). (ovid.com)
  • The focus of current study was to determine ER subtype specific expression on cSCC A431 cells and investigate if ER agonist based activation modulates tumor markers CD55 and Cyclin D1 in the cells. (tu-dortmund.de)
  • Taken together, here we demonstrate for the first time that all three ERs- ERα, ERβ and GPR30 are expressed in human A431 cSCC cells and further ER agonist based activation modulates the expression of tumor markers CD55 and Cyclin D1. (tu-dortmund.de)
  • These results suggest that OTA has cell proliferative and tumor-promoting potential in mouse skin, which involves EGFR-mediated MAPKs and Akt pathways along with NF-κB and AP-1 transcription factors and that cyclin-D1 and COX-2 are the target genes responsible for tumor-promoting activity of OTA. (oup.com)
  • Overexpression of cyclin D1 reduced STAT3-dependent gene expression in a dose-dependent manner. (sciencemag.org)
  • Dr. Pestell and colleagues developed transgenic mice that could induce cyclin D1 expression in the breast and examined cells with cyclin D1 gene deleted. (eurekalert.org)
  • Because the cyclin D1 gene has been implicated in a variety of other human cancers these findings may have broad implications for processing of non coding RNA in human tumorigenesis. (eurekalert.org)
  • Here, we show that the cyclin D1 gene is a direct target for transactivation by the β-catenin/LEF-1 pathway through a LEF-1 binding site in the cyclin D1 promoter. (pnas.org)
  • In this study, we investigated the possibility that the cyclin D1 gene is a target for the β-catenin/LEF-1 complex and show that the cyclin D1 promoter contains a LEF-1 binding sequence that is activated in human colon cancer cells. (pnas.org)
  • Cyclin D1 overexpression is a common event in cancer but does not occur solely as a consequence of gene amplification. (acronymattic.com)
  • The co-regulation of cyclin E1 and cyclin E2 with distinct gene sets could explain the different relationship of each gene to disease. (acronymattic.com)
  • Homozygous deletion of the cyclin D1 gene, enhanced expression by PPARγ ligands of PPARγ and PPARγ-responsive genes, and cyclin D1 -/- mice exhibit hepatic steatosis. (elsevier.com)
  • Lesions were analyzed for cyclin D1 gene amplification by fluorescent in-situ hybridization. (biomedcentral.com)
  • A low rate of cyclin D1 gene amplification was identified in a significant proportion of cells in the WDT-UMP lesions as compared to surrounding benign adenomatoid areas. (biomedcentral.com)
  • Overexpression of cyclin D1, associated with the amplification of the gene suggests that these WDT-UMP lesions are an intermediate between the benign and malignant groups making this group of lesions a reliable precursor of FVPTC. (biomedcentral.com)
  • Age Dependent Switching Role of Cyclin D1 in Breast Cancer," Analytical Cellular Pathology , vol. 35, no. 3, pp. 179-185, 2012. (hindawi.com)
  • The results demonstrate that not all functions of individual D cyclins are redundant, and highlight a master role of cyclin D1 in hematopoiesis. (antikoerper-online.de)
  • Because the role of cyclin D1 in the proliferative and early noninvasive stages of breast cancer is largely unknown, we examined normal breast epithelium (NBE), proliferative disease (PD), ductal carcinoma in situ (DCIS), and invasive carcinoma (IC) to evaluate the timing and possible importance of cyclin D1 expression in the development of breast cancer. (aacrjournals.org)
  • This is presumably due to the role of cyclin D1 in RB inactivation. (biologists.org)
  • Cyclin D1-CDK4 also enables the activation of cyclin E-CDK2 complex by sequestering Cip/Kip family CDK inhibitory proteins p21 and p27, allowing entry into the S phase. (wikipedia.org)
  • Cyclin D1 is a member of a superfamily of cyclins, proteins that govern transitions through distinct phases of the cell cycle by regulating CDKs. (novusbio.com)
  • The observation that PR reduces the Cyclin D1 mRNA stability led us to investigate the effects of PR on RNA binding proteins, especially those which are involved in RNA stability. (duke.edu)
  • Although the work to determine the effects of these RNA binding proteins on CyclinD1 mRNA stability is still ongoing, we have discovered a role for one of the PR-induced RNA binding proteins tristetraprolin (TTP), in the suppression of the inflammation pathway in breast cancer. (duke.edu)
  • Immunohistochemical detection of nuclear proteins cyclin D1, p53, and p16INK4A, and the Ki-67 labeling index was undertaken in tissue sections from 148 tongue cancers treated by surgical resection. (garvan.org.au)
  • Substrate specificity of S cyclins is imparted by the hydrophobic batch (centered on the MRAIL sequence), which has affinity for substrate proteins that contain a hydrophobic RXL (or Cy) motif. (wikipedia.org)
  • We have further determined that the half-life of Cyclin D1 mRNA is decreased significantly by progestin addition explaining how the levels of this mRNA following the addition of hormone are quickly attenuated. (duke.edu)
  • b) PS1-deficient cells showed higher levels of cyclin D1 mRNA. (nih.gov)
  • Expression profiling of mantle cell lymphoma revealed that predominance of the 3'UTR-deficient, short cyclin D1 mRNA isoform was associated with high cyclin D1 levels, a high "proliferation signature" and poor prognosis. (haematologica.org)
  • Design and Methods Sixty-two cases of mantle cell lymphoma were analyzed for cyclin D1 mRNA isoforms and total cyclin D1 levels by real-time reverse transcriptase polymerase chain reaction, and TP53 alterations were assessed by immunohistochemistry and molecular analysis. (haematologica.org)
  • Results Predominance of the short cyclin D1 mRNA was found in 14 (23%) samples, including four with complete loss of the standard transcript. (haematologica.org)
  • Median survival time was 34 months in patients with high mRNA expression of cyclinD1, which was shorter than in patients with low expression of cyclinD1 mRNA (41 months, X 2 = 4.071, P = 0.044). (oncotarget.com)
  • Independent of CDK, cyclin D1 binds to nuclear receptors (including estrogen receptor α, thyroid hormone receptor, PPARγ and AR ) to regulate cell proliferation, growth, and differentiation. (wikipedia.org)
  • Cyclin D1 also binds to histone acetylases and histone deacetylases to regulate cell proliferation and cell differentiation genes in the early to mid-G1 phase. (wikipedia.org)
  • In the present work we set out to examine the significance of cyclin D1-p27 Kip1 interaction in driving cell proliferation within the context of a living animal. (pnas.org)
  • We reasoned that analyses of these cyclin D1 −/− p27 −/− animals would provide a stringent test for the significance of cyclin D1-p27 Kip1 interaction in controlling the cell proliferation of various cyclin D1-dependent lineages. (pnas.org)
  • Experimental data has suggested that cyclin D1 and E mediate cell proliferation by different mechanisms in estrogen receptor (ER) positive and negative breast cancer. (kb.se)
  • To test this hypotheses in large breast cancer material and to clarify the histopathological correlations of cyclin E and D1, especially the association with proliferation, we analyzed cyclin E and D1 immunohistochemical expression on breast tumour microarrays consisting of 1348 invasive breast cancers. (kb.se)
  • In conclusion, the findings of this study show that cyclin D1 has separate roles, and proliferation is driven by different mechanisms in ER positive and negative breast cancers. (kb.se)
  • Therefore these results show that immature myeloma cells constitutively express cyclin D1 and can proliferate, and mature myeloma cells as well as normal mature plasma cells preferentially express p16 and can survive for a long time without proliferation. (nih.gov)
  • The data showed that overexpression of cyclin D1 in the initiated BPH-1 cell line increased cell proliferation rate but did not elicit tumorigenicity in vivo . (aacrjournals.org)
  • Unexpectedly, the G1 phase-specific cyclin D1 was dramatically increased by inducers of differentiation (NGF and FGF), but not by inducers of proliferation (EGF and insulin). (jneurosci.org)
  • The BEAS-2B immortalized HBE cell line was exposed to varying concentrations of erlotinib, and effects on proliferation, cell cycle distribution, G 1 cyclin expression, and cyclin D1 reporter activity were measured. (aacrjournals.org)
  • In these cases, marked repression of cyclin D1 and the proliferation marker Ki-67 was detected by immunohistochemical assays. (aacrjournals.org)
  • Predominance of the 3'UTR-deficient transcript correlates with higher cyclin D1 levels and may be a secondary contributing factor to high proliferation, but failed to reach prognostic significance in this study. (haematologica.org)
  • BACKGROUND & OBJECTIVES Cyclin D1 has been strongly implicated in cell proliferation particularly in the G1/S checkpoint of the cell cycle, and prognoses in human malignancies. (semanticscholar.org)
  • It was also observed that knocking down the messenger RNA expression of NF-κB, c-jun, c-fos, cyclin-D1 and COX-2 results in significant inhibition in OTA-induced PMKs proliferation. (oup.com)
  • In a transgenic model of chronic hepatic cyclin D1 expression, seliciclib induced hepatocyte injury and animal death, suggesting that cdk2 is required for survival of cyclin D1-expressing cells even in the absence of substantial proliferation. (lu.se)
  • Furthermore, it is essential for centrosome overduplication, proliferation and survival of hepatocytes that aberrantly express cyclin D1 in vivo. (lu.se)
  • Immunohistochemical analysis of galectin-3, HBME-1, CK19 and the proliferation markers Ki67 and cyclin D1 was performed. (biomedcentral.com)
  • The relationship between the induction of cyclin D1 and G 1 arrest defines a new cellular response to p53. (aacrjournals.org)
  • However, more recent reports suggested that the commitment to cycle in response to serum occurs already in G(2) phase and requires the Ras-dependent induction of cyclin D1, which promotes following G(1)/S transition. (cnrs.fr)
  • The more aggressive basal-like subtype of breast cancers, however, exhibited lower levels of cyclin D1 and Dicer, which would in turn globally reduce the level of mature miRNA. (eurekalert.org)
  • Indeed, overexpression of D-cyclins is seen in a large number of human cancers ( 2 , 3 ). (pnas.org)
  • For instance, cyclin D1 is overexpressed in the majority of human breast cancers ( 4 , 5 ). (pnas.org)
  • Overexpression of cyclin D1 plays important roles in the development of human cancers, including breast, colon, and melanoma ( 11 , 13 - 17 ). (aacrjournals.org)
  • Cyclin D1 which functions as a mitogenic sensor and allosteric activator of CDK4/6, is one of the more frequently altered cell cycle regulators in cancers. (pubmedcentralcanada.ca)
  • Although cyclin D1 overexpression is clearly implicated in the affected cancers, overexpression of cyclin D1 is not sufficient to drive oncogenic transformation. (pubmedcentralcanada.ca)
  • This review provides a brief overview of current data documenting various mechanisms underlying aberrant cyclin D1 regulation in human cancers and their impact on neoplastic transformation. (pubmedcentralcanada.ca)
  • Overexpression of cyclin D1 and its catalytic partner, CDK4, is frequently seen in human cancers. (sigmaaldrich.com)
  • The expression of cyclin E2, independently of cyclin E1, can be induced via cyclin D1, Chd8 and CDP/Cux, all of which are upregulated in cancers [47, 123], and cyclin E2 is also independently suppressed by the tumour suppressor p53 [89]. (acronymattic.com)
  • For example, cyclin E2, which is a target of cyclin D1 and Chd8 in estrogen-responsive cells [75], has been associated with poor outcome only in ER-positive breast cancers [106], which resembles the association of cyclin D1 overexpression . (acronymattic.com)
  • These findings define a pivotal role for cyclin D1 in a subset of mammary cancers in mice and imply a functional role for cyclin D1 overexpression in human breast cancer. (garvan.org.au)
  • Cyclin D1 and p16INK4A are molecules with pivotal roles in cell cycle control and the development of diverse human cancers, and overexpression of cyclin D1 and loss of p16INK4A expression are common genetic events in head and neck squamous cell carcinoma. (garvan.org.au)
  • In a logistic regression model, cyclin expression, early age of onset, and estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2) status were the independent factors most clearly distinguishing tumors of BRCA1 mutation carriers from other familial breast cancers. (diva-portal.org)
  • Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (wikipedia.org)
  • A number of therapeutic agents have been observed to induce cyclin D1 degradation in vitro [25-30]. (acronymattic.com)
  • Different cyclins exhibit distinct expression and degradation patterns that contribute to the coordination of the cell cycle during mitosis. (clontech.com)
  • Our results indicate a hitherto unreported role of NQO2 in the control of AKT/GSK-3β/cyclin D1 and highlight the involvement of NQO2 in degradation of cyclin D1, as part of mechanism of chemoprevention by resveratrol. (oup.com)
  • Additionally, in the presence of cyclin D1 the amount of STAT3 in the nucleus was decreased, providing a possible second mechanism whereby cyclin D1 shuttles STAT3 out of the nucleus to provide longer-term inhibition of STAT3-mediated signaling. (sciencemag.org)
  • Moreover, SNIP1 depletion results in inhibition of cyclin D1 promoter activity in a manner dependent upon a previously characterized binding site for the AP-1 transcription factor family. (nature.com)
  • Inhibition of cyclin D1 by RASSF1A occurs posttranscriptionally and is likely at the level of translational control. (asm.org)
  • Senescence triggered by cyclin D1 depletion was more extensive than that caused by the prolonged CDK4 inhibition. (biologists.org)
  • We identified a buildup of intracellular reactive oxygen species, in the cancer cells that underwent senescence upon cyclin D1 depletion, but not in CDK4 inhibition, and that ROS buildup was responsible for the senescence. (biologists.org)
  • Either wild- type or catalytically inactive CDK4 cooperates with cyclin D1 in reversing the G 1 arrest induced by inhibition of Ras activity. (elsevier.com)
  • Either wild- type or catalytically inactive CDK4 cooperates with cyclin D1 in reversing the G1 arrest induced by inhibition of Ras activity. (elsevier.com)
  • The inhibition of PPARγ function by cyclin D1 is a new mechanism of signal transduction cross talk between PPARγ ligands and mitogenic signals that induce cyclin D1. (elsevier.com)
  • Surprisingly, cdk2 ablation or inhibition led to massive hepatocyte and animal death following cyclin D1 transfection. (lu.se)
  • Recombinant human Cyclin D1 expressed in E. coli. (lsbio.com)
  • Immunohistochemical staining of cyclin D1 antibodies is used to diagnose mantle cell lymphoma. (wikipedia.org)
  • These products are affinity-purified IgG antibodies that recognize human cyclin D1. (clontech.com)
  • We analyzed the blood of patients with HLA-A2+ ccRCC for the presence of CD8+ T cells specific for TAA-derived HLA-A2-restricted peptides and found spontaneous responses to cyclin D1 in 5 of 6 patients with Cyclin D1-positive tumors. (uzh.ch)
  • PURPOSE: We analyzed the expression of critical cell cycle regulators cyclin E and cyclin D1 in familial breast cancer, focusing on BRCA mutation-negative tumors. (diva-portal.org)
  • Cyclin E expression in tumors of BRCA1 or BRCA2 carriers is higher, and cyclin D1 expression lower, than in sporadic tumors. (diva-portal.org)
  • In familial non-BRCA1/2 tumors, cyclin E and cyclin D1 expression has not been studied. (diva-portal.org)
  • EXPERIMENTAL DESIGN: Cyclin E and cyclin D1 immunohistochemical expression was studied in tissue microarrays consisting of 53 BRCA1, 58 BRCA2, 798 familial non-BRCA1/2, and 439 sporadic breast tumors. (diva-portal.org)
  • RESULTS: In univariate analysis, BRCA1 tumors had significantly more frequently high cyclin E (88%) and low cyclin D1 (84%) expression than sporadic (54% and 49%, respectively) or familial non-BRCA1/2 (38% and 45%, respectively) tumors. (diva-portal.org)
  • BRCA2 tumors had significantly more frequently low cyclin D1 expression (68%) than sporadic or familial non-BRCA1/2 tumors and significantly more frequently high cyclin E expression than familial non-BRCA1/2 tumors. (diva-portal.org)
  • High cyclin E and low cyclin D1 expression were also independent predictors of BRCA2 mutation when compared with familial non-BRCA1/2 tumors. (diva-portal.org)
  • Most interestingly, lower frequency of high cyclin E expression independently distinguished familial non-BRCA1/2 tumors also from sporadic ones. (diva-portal.org)
  • CONCLUSIONS: Cyclin E and cyclin D1 expression distinguishes non-BRCA1/2 tumors from both sporadic and BRCA1- and BRCA2-associated tumors and may reflect different predisposition and pathogenesis in these groups. (diva-portal.org)
  • These studies suggest that cdk2 may warrant further investigation as a target for therapy of liver tumors with constitutive cyclin D1 expression. (lu.se)
  • Inhibitors of β-catenin activation, wild-type adenomatous polyposis coli, axin, and the cytoplasmic tail of cadherin suppressed cyclin D1 promoter activity in colon cancer cells. (pnas.org)
  • Plasmids containing the luciferase reporter under the cyclin D1 promoter and the deletion constructions derived from it have been described ( 31 ). (pnas.org)
  • e) Enhanced β-catenin/LEF-induced activation of the cyclin D1 promoter in PS1-deficient cells. (nih.gov)
  • In addition, cyclin D1 overexpression sensitized cells to transcription inhibitors, revealing a synthetic lethality interaction that was also observed in primary mantle cell lymphoma cases. (jci.org)
  • Cyclin D1 is unsuitable for minimal residual disease monitoring in bone marrow of patients with mantle cell lymphoma. (antikoerper-online.de)
  • Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma genetically characterized by the t(11;14)(q13;q32) translocation leading to overexpression of cyclin D1 (CyD1), which is not normally expressed in lymphoid cells. (haematologica.org)
  • Cases without pathological response to erlotinib did not exhibit changes in cyclin D1 or Ki-67 immunohistochemical expression and had much lower erlotinib tissue levels than did responding cases. (aacrjournals.org)
  • Cyclin D1 immunohistochemical expression in Sudanese patients affected with prostatic carcinoma in Khartoum state. (alliedacademies.org)
  • This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. (wikipedia.org)
  • Of the G1 regulatory molecules, the cyclin D1/CDK4 complex is deregulated at a high frequency and is thought to contribute directly to neoplastic transformation and growth. (pubmedcentralcanada.ca)
  • An analysis of cell cycle markers revealed that NF-κB activates cyclin D1 expression, and the results showed that this regulatory pathway is one mechanism by which NF-κB inhibits myogenesis. (asm.org)
  • These findings advance our knowledge base of Wnt signaling in calvarial morphogenesis, suggesting a key regulatory pathway of Axin2/β-catenin/cyclin D1 in development of the suture mesenchyme. (biomedcentral.com)
  • Herein, we show that cyclin D1 enhanced H3K9 dimethylation though direct association with G9a. (jefferson.edu)
  • There is considerable specificity in which cyclin binds with CDK. (wikipedia.org)
  • Furthermore, cyclin binding determines the specificity of the cyclin-CDK complex for particular substrates. (wikipedia.org)
  • Cyclin D1 is expressed in all adult human tissues with the exception of cells derived from bone marrow stem cell lines (both lymphoid and myeloid). (wikipedia.org)
  • Endogenous cyclin D1 associated with STAT3 in cells treated for 2 hours after treatment with interleukin 6 (IL-6), an activator of STAT3. (sciencemag.org)
  • The group also examined cells lacking Dicer, and noted many similarities between Dicer-lacking and cyclin D1-lacking cells, in addition to failure of miRNA processing, suggesting a deeper connection between these two processes. (eurekalert.org)
  • Three clones, with cyclin D1 levels similar to those seen in colon cancer cell lines, were further evaluated in comparison to the vector control cells. (nih.gov)
  • D-type cyclins (cyclins D1, D2, and D3) are key components of cell cycle machinery in mammalian cells. (pnas.org)
  • a new function for cyclin D1 in the control of redox metabolism and interactions of cyclin D1 -expressing multiple myeloma cells with their bone marrow microenvironment. (antikoerper-online.de)
  • Cyclin D1 as well as D2 and D3 have central roles in linking exogenous growth regulating stimuli with the cycling machinery of cells. (novusbio.com)
  • On the other hand, mature myeloma cells did not express cyclin D1 but expressed p16, not p21 or p27, as well as normal mature plasma cells. (nih.gov)
  • This study examined the effects of manipulating cyclin D1 expression in either human prostatic epithelial or stromal cells using a tissue recombination model. (aacrjournals.org)
  • However, overexpression of cyclin D1 in normal prostate fibroblasts (NPF) that were subsequently recombined with BPH-1 did induce malignant transformation of the epithelial cells. (aacrjournals.org)
  • The present study also showed that recombination of BPH-1 + cyclin D1-overexpressing fibroblasts (NPF cyclin D1 ) resulted in permanent malignant transformation of epithelial cells (BPH-1 NPF-cyclin D1 cells) similar to that seen with carcinoma-associated fibroblasts (CAF). (aacrjournals.org)
  • Microarray analysis showed that the expression profiles between CAFs and NPF cyclin D1 cells were highly concordant including cyclin D1 up-regulation. (aacrjournals.org)
  • Overexpression of cyclin D1 has also been linked to the development of endocrine resistance in breast cancer cells [20-22]. (acronymattic.com)
  • a) Immunoblot analysis of β-catenin, cyclin D1, cyclin A, and Cdc2 from PS1+/− and −/− cells. (nih.gov)
  • β-catenin and cyclin D1 levels were elevated in PS1-deficient cells. (nih.gov)
  • Middle) Because PS1−/− cells have higher constitutive levels of cyclin D1, a shorter film exposure of the same autoradiogram that is comparable with that seen in PS+/− cells is shown. (nih.gov)
  • Bosone I, Cavalla P, Chiadò-Piat L, Vito ND, Schiffer D: Cyclin D1 expression in normal oligodendroglia and microglia cells: its use in the differential diagnosis of oligodendrogliomas. (exbio.cz)
  • D-type cyclins, which act as growth factor sensors, are not per se sufficient to keep cells in cycle and need the cooperation of other oncogenes to induce malignant transformation. (haematologica.org)
  • Lützen, A, Bisgaard, HC & Rasmussen, LJ 2004, ' Differential Cyclin D1 expression and apoptosis in DNA mismatch repair-deficient cells upon methylation and UV-C damage ', Experimental Cell Research , bind 292, s. 123-134. (ruc.dk)
  • Results Normal epidermis showed parabasal Ki67 and cyclin D1 staining while fascin labelled cells in the lower one-third of the epithelium. (bmj.com)
  • However, in 14 of 20 p16-positive SCC small infiltrative tumour groups and single infiltrating cells at the invasive front showed a cyclin D1-positive/ Ki67-negative phenotype. (bmj.com)
  • TCF1 knockdown in PyMT cells suppressed tumorsphere formation due to Cyclin D1 attenuation. (aacrjournals.org)
  • NQO2 knockdown cells also showed attenuation of resveratrol-induced downregulation of cyclin D1. (oup.com)
  • Despite the observation that cyclin D1 is a target of MEK1, in cycling cells, activated MEK1, but not cyclin D1, is capable of overcoming a G 1 arrest induced by Ras inactivation. (elsevier.com)
  • Reduction of p27 levels by expression of antisense p27 allows for S-phase entry from quiescence in NIH 3T3 cells expressing ectopic cyclin D1, but not in parental cells. (elsevier.com)
  • Despite the observation that cyclin D1 is a target of MEK1, in cycling cells, activated MEK1, but not cyclin D1, is capable of overcoming a G1 arrest induced by Ras inactivation. (elsevier.com)
  • Unlike wild-type cells, cdk2 -/- liver cells failed to undergo centrosome overduplication in response to ectopic cyclin D1 expression. (lu.se)
  • In mammalian cells, CDK1, with its partners cyclin A2 and B1, alone can drive the cell cycle. (wikipedia.org)
  • In yeast cells, it occurs before cyclin binding. (wikipedia.org)
  • Cyclin D1 plays an important role in the multi-step process of gastrointestinal tumorigenesis. (nih.gov)
  • This model may be useful for understanding the role and interrelationships of cyclin D1 in colorectal tumorigenesis. (nih.gov)
  • Dietary calcium and cholecalciferol modulate cyclin D1 expression, apoptosis, and tumorigenesis in intestine of adenomatous polyposis coli1638N/+ mice. (pubfacts.com)
  • Results from the current study suggest that cyclin D1 expression is associated with the degree of transformation and most probably plays a role in the early development of ovarian malignancy. (nih.gov)
  • These results suggest that Cyclin D1 expression may play an important role in the early stages of carcinogenesis, and that immunohistochemical detection of Cyclin D1 expression may be helpful in differentiating low-grade DCIS from ADH. (eurekamag.com)
  • PS1 deficiency results in accumulation of cytosolic beta-catenin, leading to a beta-catenin/LEF-dependent increase in cyclin D1 transcription and accelerated entry into the S phase of the cell cycle. (nih.gov)
  • A significant relationship between cyclin D1 expression and tumour proliferative activity was also found (P = 0.000001). (nih.gov)
  • The recent generation of mice wherein individual cyclins or their cognate CDKs have been eliminated from the mouse germline has revealed the potential for significant redundancy with regard to CDK function and substrate regulation. (pubmedcentralcanada.ca)
  • This is particularly evident when one considers the potential contribution of G1 cyclins and CDKs to neoplastic transformation and growth. (pubmedcentralcanada.ca)
  • The structure of human Cdk2 revealed that CDKs have a modified ATP-binding site that can be regulated by cyclin binding. (wikipedia.org)
  • A significant percentage of the cyclin D1-CDK4 complexes are associated with p27 in serum-starved activated MEK1 or cyclin D1 cell lines. (elsevier.com)
  • Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated into the nucleus through interaction with KIP/CIP family members. (bosterbio.com)
  • Cyclin-CDK complexes phosphorylate substrates appropriate for the particular cell cycle phase. (wikipedia.org)
  • Cyclin-CDK complexes of earlier cell-cycle phase help activate cyclin-CDK complexes in later phase. (wikipedia.org)
  • Tissue sections from 75 esophagogastric junction adenocarcinomas resected from 1991 to 2003 were analyzed by immunohistochemistry for p53, cyclin D1 and Bcl-2 using streptavidin-biotin-peroxidase method. (scielo.br)
  • Immunohistochemistry and fluorescence qualitative PCR was used to determine the level of p57 kip2 and cyclinD1 in GCA and its adjacent non-cancerous tissues. (oncotarget.com)
  • In addition to its role in regulating the cell cycle, cyclin D1 induces Dicer and thereby promotes the maturation of miRNA," says lead researcher Richard Pestell, M.D., Ph.D., Director of the Kimmel Cancer Center at Thomas Jefferson University and Chair of the Department of Cancer Biology. (eurekalert.org)
  • 6-Gingerol induces cell-cycle G1-phase arrest through AKT-GSK 3β-cyclin D1 pathway in renal-cell carcinoma. (greenmedinfo.com)
  • Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity by cyclin D1. (jefferson.edu)
  • Endogenous cyclin D1 was required for the recruitment of G9a to target genes in chromatin, for G9a-induced H3K9me2 of histones, and for NL-LAD interaction. (jefferson.edu)
  • Mechanistically, circMYLK can serve as a competing endogenous RNA for miR-195 to increase cyclin D1 expression in LSCC, and rescue experiments further showed that restoration of miR-195 could block the oncogenic role of circMYLK in LSCC. (portlandpress.com)
  • Depletion of cyclin D1 promotes the RB-independent pro-senescence pathway, and cancer cell succumbing to the endogenous oxidative stress. (biologists.org)
  • Amplification of EGFR and cyclin D1 genes associated with human papillomavirus infection in oral squamous cell carcinoma. (semanticscholar.org)
  • These results define both a new function for SNIP1 and identify a previously unrecognized regulator of the cell cycle and cyclin D1 expression. (nature.com)
  • We show that the cyclin D1 oncoprotein targets hexokinase 2 (HK2), a major glycolysis regulator, through two original molecular mechanisms in the cytoplasmic and nuclear compartments. (archives-ouvertes.fr)
  • The present study aimed to evaluate the role of a cell cycle regulator like cyclin D1 in these tumours along with assessment of other well established PTC markers like galectin-3, HBME-1, CK19. (biomedcentral.com)
  • Cyclin D1 interacts with CDK4 and CDK6, whose activity is required for the cell cycle G1/S transition. (clontech.com)
  • A prospective, open label, parallel, interventional, randomized control trial on TPF induction chemotherapy indicate there is no difference in overall survival, disease free survival, local regional recurrence free survival and metastasis free survival between experimental group and control group, however, the subgroup analysis proves that the induction chemotherapy of TPF protocol could benefit the patients with cyclinD1 high expression and cN2 locally advanced oral squamous cell carcinoma. (clinicaltrials.gov)
  • Thus, we sought to determine the relationship between cyclin D1 and/or p16INK4A expression and disease outcome in squamous cell carcinoma of the anterior tongue. (garvan.org.au)
  • These data indicate that cyclin D1 overexpression and loss of p16INK4A expression predict early relapse and reduced survival in squamous cell carcinoma of the anterior tongue. (garvan.org.au)
  • We investigated the correlation between cyclin D1 overexpression and clinicopathological features as well as cell cycle parameters to understand its clinical significance in patients with tobacco-related oral squamous cell carcinoma (OSCC). (semanticscholar.org)
  • p53, Cyclin D1, p21 (WAF1) and Ki-67 (MIB1) Expression at Invasive Tumour Fronts of Oral Squamous Cell Carcinomas and Development of Local Recurrence', Asian Pacific Journal of Cancer Prevention , 17(3), pp. 1243-1249. (waocp.org)
  • Background: Expression of p53, cyclin D1, p21 (WAF1) and Ki-67 (MIB1) was evaluated in oral squamous cell carcinoma (OSCC) to test whether levels of these markers at invasive tumour fronts (ITFs) could predict the development of local recurrence. (waocp.org)
  • Conclusions: Assessment of p53, cyclin D1, p21 (WAF1), and Ki-67 (MIB1) at the ITF could help to predict local recurrence in early stage oral squamous cell carcinoma cases. (waocp.org)
  • Consistent with results obtained with the C2C12 differentiation model, we show that NF-κB also promotes cell growth in embryonic fibroblasts, correlating with its regulation of cyclin D1. (asm.org)
  • These data demonstrate that p21 promotes a CSC-like phenotype via activation of Wnt/TCF1/Cyclin D1 signaling. (aacrjournals.org)
  • Rather, emerging evidence suggests that nuclear retention of cyclin D1 resulting from altered nuclear trafficking and proteolysis is critical for the manifestation of its oncogenicity. (pubmedcentralcanada.ca)
  • Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclea" by Chenguang Wang, Zhiping Li et al. (jefferson.edu)
  • Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function. (jefferson.edu)
  • Cyclin D1 abundance thus coordinates nuclear DNA synthesis and mitochondrial function. (jefferson.edu)
  • All of the primary human prostatic cancer samples revealed in different ranges of intensity from weak (+1), moderate (+2) to strongly positive nuclear staining (+3) for Cyclin D1. (alliedacademies.org)
  • Reactive and dVIN specimens demonstrated mildly increased Ki67 and cyclin D1 expression that maintained parabasal polarity, whereas uVIN and p16-positive SCC were characterised by loss of cyclin D1 staining. (bmj.com)
  • Interestingly, it was determined that progestin mediated up- regulation of Cyclin D1 is rapid, peaking at 6hrs post hormone addition followed by a decrease in expression reaching a nadir at 18hrs. (duke.edu)
  • Translational Regulation of Cyclin D1 by 15-Deoxy-{Delta}12,14-Prostaglandin J2 -- Campo et al. (aacrjournals.org)
  • High cyclin E expression is common in hormone receptor negative and high grade aggressive breast cancer, whereas cyclin D1 in hormone receptor positive and low grade breast cancer. (kb.se)
  • Oncogenic transformation of normal enterocytes by overexpression of cyclin D1. (nih.gov)
  • The cyclin D1-CDK4 oncogenic interactome enables identification of potential novel oncogenes and clinical prognosis. (sigmaaldrich.com)