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.

Cytokinin activation of Arabidopsis cell division through a D-type cyclin. (1/335)

Cytokinins are plant hormones that regulate plant cell division. The D-type cyclin CycD3 was found to be elevated in a mutant of Arabidopsis with a high level of cytokinin and to be rapidly induced by cytokinin application in both cell cultures and whole plants. Constitutive expression of CycD3 in transgenic plants allowed induction and maintenance of cell division in the absence of exogenous cytokinin. Results suggest that cytokinin activates Arabidopsis cell division through induction of CycD3 at the G1-S cell cycle phase transition.  (+info)

FLI-1 inhibits differentiation and induces proliferation of primary erythroblasts. (2/335)

Friend virus-induced erythroleukemia involves two members of the ETS family of transcriptional regulators, both activated via proviral insertion in the corresponding loci. Spi-1/PU.1 is expressed in the disease induced by the original Friend virus SFFV(F-MuLV) complex in adult mice. In contrast, FLI-1 is overexpressed in about 75% of the erythroleukemias induced by the F-MuLV helper virus in newborn mice. To analyse the consequences of the enforced expression of FLI-1 on erythroblast differentiation and proliferation and to compare its activity to that of PU.1/Spi-1, we used a heterologous system of avian primary erythroblasts previously described to study the cooperation between Spi-1/PU.1 and the other molecular alterations observed in SFFV-induced disease. FLI-1 was found: (i) to inhibit the apoptotic cell death program normally activated in erythroblasts following Epo deprivation; (ii) to inhibit the terminal differentiation program induced in these cells in response to Epo and; (iii) to induce their proliferation. However, in contrast to Spi-1/PU.1, the effects of FLI-1 on erythroblast, differentiation and proliferation did not require its cooperation with an abnormally activated form of the EpoR. Enhanced survival of FLI-1 expressing erythroblasts correlated with the upregulation of bcl2 expression. FLI-1 also prevented the rapid downregulation of cyclin D2 and D3 expression normally observed during Epo-induced differentiation and delayed the downregulation of several other genes involved in cell cycle or cell proliferation control. Our results show that overexpression of FLI-1 profoundly deregulates the normal balance between differentiation and proliferation in primary erythroblasts. Thus, the activation of FLI-1 expression observed at the onset of F-MuLV-induced erythroleukemia may provide a proliferative advantage to virus infected cells that would otherwise undergo terminal differentiation or cell death.  (+info)

Cyclin D1 and D3 associate with the SCF complex and are coordinately elevated in breast cancer. (3/335)

D-type cyclins are important cell cycle regulators that promote cellular proliferation in response to growth factors by inactivation of the retinoblastoma protein (Rb). Cyclin D1 has been shown to be overexpressed in several cancer types and to act as an oncogene in breast cancers. As D-type cyclins are rate limiting for progression into S phase, the level at which they accumulate must be carefully regulated. Several mechanisms leading to overexpression of cyclin D1 have been reported including amplification, translocation and stabilization of the mRNA. Here, we present data showing elevated cyclin D1 protein in breast cancer samples in the absence of elevated mRNA level. Further, we found that in these cases, cyclin D3 protein also accumulates and that the coordinate increase in cyclin D1 and D3 occurs in 15% (7/47) of breast cancers. In addition we show that blocking the activity of the 26S proteosome results in the accumulation of cyclin D1 and D3, that both D-type cyclins are ubiquitinated and associate with Cul-1, a component of the SCF ubiquitin ligase complex. Finally, we show that the coordinated elevation of cyclin D1 and D3 is also observed in the breast cell line MCF-7 and demonstrate that the degradation of cyclin D1 and D3 is deficient in this cell line. These results indicate that cyclin D1 and cyclin D3 share a common mechanism of degradation and we propose that the coordinate increase of D-type cyclins observed in primary breast cancers reflects a defect in their proteolysis.  (+info)

CTLA-4-Mediated inhibition of early events of T cell proliferation. (4/335)

CTLA-4 engagement by mAbs inhibits, while CD28 enhances, IL-2 production and proliferation upon T cell activation. Here, we have analyzed the mechanisms involved in CTLA-4-mediated inhibition of T cell activation of naive CD4+ T cells using Ab cross-linking. CTLA-4 ligation inhibited CD3/CD28-induced IL-2 mRNA accumulation by inhibiting IL-2 transcription, which appears to be mediated in part through decreasing NF-AT accumulation in the nuclei. However, CTLA-4 ligation did not appear to affect the CD28-mediated stabilization of IL-2 mRNA. Further, CTLA-4 engagement inhibited progression through the cell cycle by inhibiting the production of cyclin D3, cyclin-dependent kinase (cdk)4, and cdk6 when the T cells were stimulated with anti-CD3/CD28 and with anti-CD3 alone. These results indicate that CTLA-4 signaling inhibits events early in T cell activation both at IL-2 transcription and at the level of IL-2-independent events of the cell cycle, and does not simply oppose CD28-mediated costimulation.  (+info)

D-type cyclins complex with the androgen receptor and inhibit its transcriptional transactivation ability. (5/335)

D-type cyclins regulate distinct cellular processes, such as mitotic cell cycle control, differentiation, and transcription. We have previously shown that the D-type cyclins are critical for the androgen-dependent proliferation of prostate cells. Here, we sought to determine whether cyclin D1 directly influences the transactivation potential of the androgen receptor, a transcription factor that strongly influences androgen-dependent proliferation. We found that ligand-mediated transcriptional activation of a physiological target, prostate-specific antigen, by the androgen receptor was inhibited by cyclins D1 and D3. The ability of D-type cyclins to inhibit androgen receptor transactivation was not shared with other cyclins, and cyclin D1 was as effective as dominant negative mutants of the androgen receptor in inhibiting transactivation. This function of cyclin D1 was independent of its role in cell cycle progression and is likely elicited through its ability to form a specific complex with the androgen receptor. These data underscore the various mechanisms through which the androgen receptor is regulated and also point to a negative feedback role for cyclin D1 in controlling androgen-dependent growth.  (+info)

The transition from proliferation to differentiation is delayed in satellite cells from mice lacking MyoD. (6/335)

Satellite cells from adult rat muscle coexpress proliferating cell nuclear antigen and MyoD upon entry into the cell cycle, suggesting that MyoD plays a role during the recruitment of satellite cells. Moreover, the finding that muscle regeneration is compromised in MyoD-/- mice, has provided evidence for the role of MyoD during myogenesis in adult muscle. In order to gain further insight into the role of MyoD during myogenesis in the adult, we compared satellite cells from MyoD-/- and wildtype mice as they progress through myogenesis in single-myofiber cultures and in tissue-dissociated cell cultures (primary cultures). Satellite cells undergoing proliferation and differentiation were traced immunohistochemically using antibodies against various regulatory proteins. In addition, an antibody against the mitogen-activated protein kinases ERK1 and ERK2 was used to localize the cytoplasm of the fiber-associated satellite cells regardless of their ability to express specific myogenic regulatory factor proteins. We show that during the initial days in culture the myofibers isolated from both the MyoD-/- and the wildtype mice contain the same number of proliferating, ERK+ satellite cells. However, the MyoD-/- satellite cells continue to proliferate and only a very small number of cells transit into the myogenin+ state, whereas the wildtype cells exit the proliferative compartment and enter the myogenin+ stage. Analyzing tissue-dissociated cultures of MyoD-/- satellite cells, we identified numerous cells whose nuclei were positive for the Myf5 protein. In contrast, quantification of Myf5+ cells in the wildtype cultures was difficult due to the low level of Myf5 protein present. The Myf5+ cells in the MyoD-/- cultures were often positive for desmin, similar to the MyoD+ cells in the wildtype cultures. Myogenin+ cells were identified in the MyoD-/- primary cultures, but their appearance was delayed compared to the wildtype cells. These "delayed" myogenin+ cells can express other differentiation markers such as MEF2A and cyclin D3 and fuse into myotubes. Taken together, our studies suggest that the presence of MyoD is critical for the normal progression of satellite cells into the myogenin+, differentiative state. It is further proposed that the Myf5+/MyoD- phenotype may represent the myogenic stem cell compartment which is capable of maintaining the myogenic precursor pool in the adult muscle.  (+info)

Mpl ligand enhances the transcription of the cyclin D3 gene: a potential role for Sp1 transcription factor. (7/335)

Cyclin D3 plays a major role in the development of polyploidy in megakaryocytes. The expression of cyclin D3 gene and the level of cyclin D3 protein are increased by the Mpl ligand in the Y10/L8057 megakaryocytic cell line, as indicated by Northern and Western blot analyses, and by nuclear run-on assays and transfection experiments with cyclin D3 promoter constructs. DNase I footprinting of the promoter region showed protected segments, at -75 to -60 bp and at -134 to -92 bp, which display binding sites for the Sp family of transcription factors. Gel mobility shift assay and supershifts with specific antibodies indicate that Sp1 binds to these regions in the cyclin D3 promoter and that Sp1 binding activity is significantly increased by Mpl ligand. Mutation of either Sp1 site both decreases the basal promoter activity and eliminates the induction by Mpl ligand. We find that the nonphosphorylated form of SP1 has greater affinity for the cyclin D3 promoter and that the majority of Sp1 in the cells is nonphosphorylated. Mpl ligand treatment results in increased levels of Sp1 protein, which also appears as nonphosphorylated. Okadaic acid, which inhibits protein phosphatase 1 (PP1) and shifts Sp1 to a phosphorylated form, decreases cyclin D3 gene expression and suppresses Mpl ligand induction. Our data point to the potential of Mpl ligand to activate at once several Sp1-dependent genes during megakaryopoiesis.  (+info)

Involvement of p21(WAF1/Cip1) and p27(Kip1) in intestinal epithelial cell differentiation. (8/335)

Using the conditionally immortalized human cell line tsFHI, we have investigated the role of cyclin-dependent kinase inhibitors (CKIs) in intestinal epithelial cell differentiation. Expression of cyclins, cyclin-dependent kinases (Cdk), and CKIs was examined under conditions promoting growth, growth arrest, or expression of differentiated traits. Formation of complexes among cell cycle regulatory proteins and their kinase activities were also investigated. The tsFHI cells express three CKIs: p16, p21, and p27. With differentiation, p21 and p27 were strongly induced, but with different kinetics: the p21 increase was rapid but transient and the p27 increase was delayed but sustained. Our results suggest that the function of p16 is primarily to inhibit cyclin D-associated kinases, making tsFHI cells dependent on cyclin E-Cdk2 for pRb phosphorylation and G1/S progression. Furthermore, they indicate that p21 is the main CKI involved in irreversible growth arrest during the early stages of cell differentiation in association with D-type cyclins, cyclin E, and Cdk2, whereas p27 may induce or stabilize expression of differentiated traits acting independently of cyclin-Cdk function.  (+info)

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 ...
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.
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, ...
D-type cyclins (cyclin D1, D2 and D3) are components of the core cell cycle machinery. Rearrangements of cyclin D genes and overexpression of cyclin D proteins...
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 ...
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View mouse Ccndbp1 Chr2:121008403-121016904 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
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 ...
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.. ...
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- ...
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 ...
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 ...
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 ...
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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.
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
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 ...
Sabath, D.F.; Drachman, J.G.; Kaushansky, K.; Broudy, V.C., 1994: Development of a cell line dependent on MPL ligand for proliferation
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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 ...
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 ...
Progress through the G1phase of the mammalian cell cycle is regulated by the ordered synthesis, assembly, and activation of distinct cyclin-CDK holoenzymes (45, 46). Cyclins D1, D2, and D3 are up-regulated as cells exit from quiescence and associate with their major kinase partners CDK4 and CDK6 (3, 29, 32, 53). These two kinase molecules are highly homologous and associate exclusively with the D-type cyclins (3). Numerous studies have implicated cyclin D-CDK4-CDK6 complexes as key regulators of the cell cycle up to a hypothetical point during late G1 (24, 25), the restriction point, when hyperphosphorylation and inactivation of the retinoblastoma tumor suppressor gene product, pRB, occur (37, 44).. In contrast to mitotic cyclin-CDK complexes, the D-type cyclins do not automatically assemble into complexes with either CDK4 or CDK6. For example, when overexpressed in NIH 3T3 cells in the absence of serum, D-type cyclins and CDK4 do not interact efficiently (30). Hence, assembly of D-type cyclins ...
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 ...
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. ...
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
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
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 ...
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 ...
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 ...
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 ...
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its induction represents a mechanism by which myeloma cells can induce cyclin D2 dysregulation, and contribute to disease pathogenesis ...
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 ...
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.. ...
Home » meis1 regulates cyclin D1 and c-myc expression, and controls the proliferation of the multipotent cells in the early developing zebrafish ...
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.
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
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Proliferation is accelerated in GSK3β inhibitor treated mice compared to similarly injured, but vehicle treated micea) Cyclin D1, c-myc and β-catenin levels b
ATACAGGAAG TGACGATACT TTTGGCGCGC GCGGTTGCTG TTTCTTCTCT GGCTCCGGGA CCGGCGGCGG CGGCGGCGGC ACGGGCGGCG GCGTAGGGTG ^1 ^11 ^21 ^31 ^41 ^51 ^61 ^71 ^81 ^91 TTTTAACTCA AATGGGTGAT GAAAAGGACT CTTGGAAAGT GAAAACTTTA GATGAAATTC TTCAGGAAAA GAAACGAAGG AAGGAACAAG AGGAGAAAGC ^101 ^111 ^121 ^131 ^141 ^151 ^161 ^171 ^181 ^191 AGAGATAAAA CGCTTAAAAA ATTCTGATGA CCGGGATTCC AAGCGGGATT CCCTTGAGGA GGGGGAGCTG AGAGATCACT GCATGGAGAT CACAATAAGG ^201 ^211 ^221 ^231 ^241 ^251 ^261 ^271 ^281 ^291 AACTCCCCGT ATAGAAGAGA AGACTCTATG GAAGACAGAG GAGAAGAAGA TGATTCTTTG GCCATCAAAC CACCCCAGCA AATGTCTCGG AAAGAAAAAG ^301 ^311 ^321 ^331 ^341 ^351 ^361 ^371 ^381 ^391 TTCATCACAG AAAAGATGAA AAGAGAAAAG AGAAAAAGCA TGCTAGAGTG AAGAAGAAAG AAAGAGAGCA CGAACGTCGG AAACGACATC GAGAAGAACA ^401 ^411 ^421 ^431 ^441 ^451 ^461 ^471 ^481 ^491 GGATAAAGCT CGCCGGGAAT GGGAAAGACA GAAGAGAAGG GAAATGGCAA GGGAGCATTC CAGGAGAGAA AGGGGGAATG ATGGCGTGTG CCTCTTCAGG ^501 ^511 ^521 ^531 ^541 ^551 ^561 ^571 ^581 ^591 GACCGCTTGG AGCAGTTAGA AAGGAAGCGG GAGCGGGAGC GCAAGATGCG ...
Cyclin D1 and p16 are involved in the regulation of G1 checkpoint and may play an important role in the tumorigenesis of nasopharyngeal carcinoma (NPC). Previous studies have examined the level of expression of cyclin D1 and p16 in primary untreated NPC but no such information is available for recurrent NPC. We set out in this study to examine the expression level of cyclin D1 and p16 in recurrent NPC that have failed previous treatment with radiation +/- chemotherapy. A total of 42 patients underwent salvage nasopharyngectomy from 1984 to 2001 for recurrent NPC after treatment failure with radiation +/- chemotherapy. Twenty-seven pathologic specimens were available for immunohistochemical study using antibodies against cyclin D1 and p16. Positive expression of cyclin D1 was observed in 7 of 27 recurrent NPC specimens (26%) while positive p16 expression was seen in only 1 of 27 recurrent NPC (4%). While the level of expression of cyclin D1 in recurrent NPC was similar to that of previously untreated
Cyclin D1 and p16 are involved in the regulation of G1 checkpoint and may play an important role in the tumorigenesis of nasopharyngeal carcinoma (NPC). Previous studies have examined the level of expression of cyclin D1 and p16 in primary untreated NPC but no such information is available for recurrent NPC. We set out in this study to examine the expression level of cyclin D1 and p16 in recurrent NPC that have failed previous treatment with radiation +/- chemotherapy. A total of 42 patients underwent salvage nasopharyngectomy from 1984 to 2001 for recurrent NPC after treatment failure with radiation +/- chemotherapy. Twenty-seven pathologic specimens were available for immunohistochemical study using antibodies against cyclin D1 and p16. Positive expression of cyclin D1 was observed in 7 of 27 recurrent NPC specimens (26%) while positive p16 expression was seen in only 1 of 27 recurrent NPC (4%). While the level of expression of cyclin D1 in recurrent NPC was similar to that of previously untreated
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 ...
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% ...
Changes to cell cycle-regulating machinery that occur during differentiation of cells are thought to be responsible mostly for withdrawal from cycling. Here, embryonal carcinoma (EC) cell lines were found that differ in their basal levels of p27 inhibitor of cyclin-dependent kinases but not in their growth rates, distribution of cells in phases of cell cycle, and their ability to differentiate. High basal levels of p27 did not substitute for up-regulation of p27 that in EC cells normally occurs early after entering a differentiation pathway. Under both standard and differentiation-supporting culture conditions, variances in the levels of p27 were strictly followed by variances in the levels of cyclins D2 and D3. In EC cells genetically manipulated to overexpress p27 protein, cyclin D3 became up-regulated and vice versa. Supposedly, titration of p27 by D-type cyclins, which prevents its inhibitory action toward cyclin-dependent kinase 2, allows for the maintenance of elevated p27 in proliferating ...
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 ...
CYCD3;1 expression in Arabidopsis is associated with proliferating tissues such as meristems and developing leaves but not with differentiated tissues. Constitutive overexpression of CYCD3;1 increases CYCD3;1-associated kinase activity and reduces the proportion of cells in the G1-phase of the cell cycle. Moreover, CYCD3;1 overexpression leads to striking alterations in development. Leaf architecture in overexpressing plants is altered radically, with a failure to develop distinct spongy and palisade mesophyll layers. Associated with this, we observe hyperproliferation of leaf cells; in particular, the epidermis consists of large numbers of small, incompletely differentiated polygonal cells. Endoreduplication, a marker for differentiated cells that have exited from the mitotic cell cycle, is inhibited strongly in CYCD3;1-overexpressing plants. Transcript analysis reveals an activation of putative compensatory mechanisms upon CYCD3;1 overexpression or subsequent cell cycle activation. These ...
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. ...
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 ...
Cyclin E (G1/S-Phase Cyclin) MonoSpecific Antibody. Reactivity Human. Tested In IHC. Formats Unconjugated. Isotype IgG, kappa. From: $199.
Lin J, Jinno S, Okayama H (2001). "Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's ... cyclin-dependent protein serine/threonine kinase regulator activity. • protein binding. • ATP binding. • cyclin binding. • ... Zhang Q, Wang X, Wolgemuth DJ (1999). "Developmentally regulated expression of cyclin D3 and its potential in vivo interacting ... Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 ...
... *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... cyclin D (Cdk4) cyclin E (Cdk2) cyclin E, A (Cdk2,1) cyclin A, ... 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 ... G1 cyclins, G1/S cyclins, S cyclins, and M cyclins. This division is useful when talking about most cell cycles, but it is not ...
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 ...
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. *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, ...
Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ...
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 ... 14 38.73 cM,14 D3. Start. 73,183,673 bp[2]. End. 73,325,822 bp[2]. ... 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 ...
Sustained D1 receptor activity is kept in check by Cyclin-dependent kinase 5. Dopamine receptor activation of Ca2+/calmodulin- ... Suzuki M, Hurd YL, Sokoloff P, Schwartz JC, Sedvall G (1998). "D3 dopamine receptor mRNA is widely expressed in the human brain ... 2003). "Relationship between functional dopamine D2 and D3 receptors gene polymorphisms and neuroleptic malignant syndrome". Am ... "Adaptive increase in D3 dopamine receptors in the brain reward circuits of human cocaine fatalities". J. Neurosci. 16 (19): ...
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
"CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle progression". Cell. 151 (6): 1308-18. doi ...
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". ... gen CCND3 kodujący cyklinę D3[75][120], gen CDC5L wpływający na regulację cyklu komórkowego[121] i gen RUNX2 wpływający na ...
Takahashi-Yanaga F, Sasaguri T (Apr 2008). "GSK-3beta regulates cyclin D1 expression: a new target for chemotherapy". Cellular ...
4,4 D3. Start. 140,961,203 bp[2]. End. 140,979,193 bp[2]. Gene ontology. ...
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 ...
8 D3,8 53.18 cM. Start. 106,603,351 bp[2]. End. 106,670,246 bp[2]. ...
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. • ...
The first to be discovered was its capability to drive cell proliferation (upregulates cyclins, downregulates p21), but it also ...
negative regulation of cyclin-dependent protein serine/threonine kinase activity. • lung development. • cytokine-mediated ...
Rabbit polyclonal Cyclin D3/CCND3 antibody. Validated in WB, ICC/IF and tested in Human. Immunogen corresponding to recombinant ... Anti-Cyclin D3/CCND3 antibody. See all Cyclin D3/CCND3 primary antibodies. ... Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 ... Belongs to the cyclin family. Cyclin D subfamily.. Contains 1 cyclin N-terminal domain. ...
Bob Weinbergs lab contains the insert cyclin D3 and is published in Cell. 1992 Sep 18. 70(6):993-1006. This plasmid is ... Rc/CMV cyclin D3 was a gift from Bob Weinberg (Addgene plasmid # 10912 ; http://n2t.net/addgene:10912 ; RRID:Addgene_10912) ... Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. Hinds PW, Mittnacht S, Dulic V, Arnold A ... Plasmid Rc/CMV cyclin D3 from Dr. ...
Rabbit polyclonal Cyclin D3 (phospho T283) antibody validated for WB and tested in Human, Mouse and Rat. Immunogen ... Anti-Cyclin D3 (phospho T283) antibody. See all Cyclin D3 primary antibodies. ... Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 ... Belongs to the cyclin family. Cyclin D subfamily.. Contains 1 cyclin N-terminal domain. ...
Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 ... Regulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) ... The cyclin subunit imparts substrate specificity to the complex. Interacts with ATF5. Interacts with EIF3K. Component of the ... Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, ...
Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 ... Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, ... Regulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) ... IPR013763. Cyclin-like. IPR036915. Cyclin-like_sf. IPR004367. Cyclin_C-dom. IPR015451. Cyclin_D. IPR006671. Cyclin_N. ...
The human cyclin D3 gene has a TATA-less promoter and a single dominant initiation site. The minimal cyclin D3 promoter ... I have been defining the cis-acting elements and trans-acting factors that control transcription of the human cyclin D3 gene in ... Genomic clones for the human cyclin D3 gene, isolated from a human chromosome 6 library, were analysed by restriction ... reporter constructs containing sequential deletions of the cyclin D3 promoter defined positively and negatively regulated ...
Proteintech Anti-Cyclin D3 Monoclonal (1F2C6), Catalog # 66357-1-IG. Tested in Western Blot (WB) and Immunohistochemistry ( ... Protein Aliases: CCND 3; CGD3; CyclinD3; D3 type cyclin; D3-type cyclin; G1/S-specific cyclin-D3; OTTHUMP00000223415; RP5- ... Cyclin D3 is a G1 cyclin closely related to Cyclins D1 and D2 phase progression. Like Cyclin D1 and Cyclin D2, it is activated ... Cite Cyclin D3 Monoclonal Antibody (1F2C6). The following product was used in this experiment: Cyclin D3 Monoclonal Antibody ( ...
Selected quality suppliers for anti-Cyclin D3 antibodies. ... Order monoclonal and polyclonal Cyclin D3 antibodies for many ... Protein level used designations for anti-Cyclin D3 (CCND3) Antibodies cyclin D3 , G1/S-specific cyclin-D3 , D3-type cyclin , G1 ... Top referenced anti-Cyclin D3 Antibodies. Show all anti-Cyclin D3 (CCND3) Antibodies with Pubmed References. * Human Monoclonal ... Browse our anti-Cyclin D3 (CCND3) Antibodies. Full name:. anti-Cyclin D3 Antibodies (CCND3). On www.antibodies-online.com are ...
Compare and order Cyclin D3 ELISA Kits. View citations, images, detection ranges, sensitivity, prices and more. Recommended ... cyclin D3 , G1/S-specific cyclin-D3 , D3-type cyclin , G1/S-specific cyclin D3 ... Cyclin D3 in Cell Division Cycle * Cyclin D3 in Cell Division Cycle ... Cyclin D3 Antigen Profile Antigen Summary The protein encoded by this gene belongs to the highly conserved cyclin family, whose ...
... cyclin D3) for ICC/IF, IHC-P, WB. Anti-Cyclin D3 pAb (GTX101522) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance. ... CCND3 antibody, G1/S-specific cyclin-D3 antibody, G1/S-specific cyclin D3 antibody, D3-type cyclin antibody, cyclin D3 antibody ... Cyclin D3 antibody detects Cyclin D3 protein at cytoplasm and nucleus by immunofluorescent analysis.. Sample: HeLa cells were ... Green: Cyclin D3 protein stained by Cyclin D3 antibody (GTX101522) diluted at 1:200.. Red: phalloidin, a cytoskeleton marker, ...
Galectin-3 and Cyclin D3 Immunohistochemistry and Tumor Dimensions Are Useful in Distinguishing Follicular Oncocytic Carcinomas ... G. Troncone, A. Iaccarino, M. Russo et al., "Accumulation of p27(kip1) is associated with cyclin D3 overexpression in the ... G. Troncone, M. Volante, A. Iaccarino et al., "Cyclin D1 and D3 overexpression predicts malignant behavior in thyroid fine- ... L. A. Erickson, L. Jin, J. R. Goellner et al., "Pathologic features, proliferative activity, and cyclin D1 expression in ...
"Cyclin D3" by people in this website by year, and whether "Cyclin D3" was a major or minor topic of these publications. ... A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development. ... "Cyclin D3" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases. Blood. 2009 Feb 19; ...
We report that cyclin D3 is rate limiting for G1 progression in thyroid follicular cells and that its constitutive upregulation ... Accordingly, PC Cl 3 cells engineered to overexpress cyclin D3 (PC-D3 cells) show enhanced growth rate and elude hormone- ... Interference with the expression of G1 cyclins (in particular cyclin D3) by the antisense methodology strongly reduced TSH- ... we demonstrate that cyclin D3 is a key mediator of TSH-dependent proliferation of thyroid follicular cells also in vivo. Cyclin ...
GFP vector and cyclin D3 (Cyclin D3), or PTEN and cyclin D3 (PTEN + Cyclin D3). Twenty-four h after transduction, the DNA ... If decreased cyclin D3 expression is required for PTEN-induced cell cycle arrest, then enforced expression of cyclin D3 should ... cyclin D3 levels remained unchanged (Fig. 7) ⇓ . Therefore, decreased levels of cyclin D3 were directly associated with cell ... 250 anti-cyclin D1 (Santa Cruz Biotechnology); 1:250 anti-cyclin D2 (Santa Cruz Biotechnology); or 1:250 anti-cyclin D3 (Santa ...
To determine the role of the cyclin D3 3′-UTR on the cyclin D3 mRNA instability induced by the L-Arg deprivation, the cyclin D3 ... A, Similar expression of cyclin D3 in selected clones of EBV cells transfected with cyclin D3 ORF or cyclin D3 cDNA plasmids. B ... Transfection of cells with cyclin D3 open reading frame or cyclin D3 cDNA. Cyclin D3-negative cell line EBV-Em, generated ... This was the result of a decreased cyclin D3 mRNA stability and a diminished cyclin D3 translation. The arrest in cyclin D3 ...
By using Jurkat cells as a model system, we have been able to demonstrate that cyclin D3 is reduced at the level of translation ... leads to down-regulation of cyclin D3 in lymphocytes. ... Cyclic AMP inhibits translation of cyclin D3 in T lymphocytes ... By using Jurkat cells as a model system, we have been able to demonstrate that cyclin D3 is reduced at the level of translation ... Taken together, it appears that activation of PKA in Jurkat cells reduces the expression of cyclin D3 at the level of ...
Furthermore, ppd and ninja mutants have a similar increase in the expression of CYCLIN D3;2 (CYCD3;2), and ectopic ... Arabidopsis Leaf Flatness Is Regulated by PPD2 and NINJA through Repression of CYCLIN D3 Genes. Alexandra Baekelandt, Laurens ... S4D). Arabidopsis has three D3-type cyclins, which were considered previously to act redundantly (Dewitte et al., 2007). In ... Arabidopsis Leaf Flatness Is Regulated by PPD2 and NINJA through Repression of CYCLIN D3 Genes ...
In the present work, we present novel evidence that a second G(1) cyclin, cyclin D3, is also potently activated by E2F1. First ... Second, all of the growth-stimulatory members of the E2F family (E2F1, -2, and -3A) potently activate a cyclin D3 promoter ... Furthermore, trans-activation of cyclin D3 by ER-E2F1 occurs even in the presence of the protein synthesis inhibitor ... Finally, mapping experiments localize the essential E2F regulatory element of the cyclin D3 promoter to a noncanonical E2F site ...
Inhibition of human CDK4/cyclin D3 expressed in Escherichia coli using retinoblastoma (386 to 928 residues) as substrate after ...
Fig. 8. The parameters of proliferation in control and differentiating A.1 and 1.3 EC cells. EC cells of both lines seeded in the same densities (2.5 x 103 cells/cm2) were cultured with and without 10-6 M RA for 24, 48, 72, and 96 h, respectively. A, growth rates. Cells were lysed in SDS-containing buffer, and the total amounts of protein were used as a measure of cell quantities. Micrograms of total protein are shown on the Y axis. Data are presented as the means of three independent experiments; bars, SE. B, the distribution of cells in cell cycle phases. Cells were fixed in Vindelov s solution, stained with propidium iodide, and analyzed using FACSCalibur equipped with ModFit 2.0 software. The percentages of cells in G1, S, and G2 phases are expressed as the means of three independent experiments; bars, SE.. ...
Early Cycling-independent Changes to p27, Cyclin D2, and Cyclin D3 in Differentiating Mouse Embryonal Carcinoma Cells1 Helena ... cyclin D3 became up-regulated and vice versa. Supposedly, titration of p27 by D-type cyclins, which prevents its inhibitory ... variances in the levels of p27 were strictly followed by variances in the levels of cyclins D2 and D3. In EC cells genetically ... Here, embryonal carcinoma (EC) cell lines were found that differ in their basal levels of p27 inhibitor of cyclin-dependent ...
D3, estrogen receptor-alpha (ERalpha) and progesterone receptor (PR). However, cyclin D3 expression, unlike D1, was confined ... The expression of cyclins D1 and D3 was examined during estradiol-17beta (E(2))-induced mammary tumorigenesis in female August ... Western blot analysis of the E(2)-induced MGTs revealed a marked rise in cyclins D1 (24-fold), D3 (9-fold) and cdk4 (3-fold) ... The kinase activity for cyclins D1 and D3, using retinoblastoma (Rb) as a substrate, in E(2)-induced MGTs and their binding to ...
anti-Cyclin D3, pAb is a polyclonal antibody that crossreacts with human, mouse protein. Works in WB, IP. Important for ... Cyclin D3, ~34kDa, is a member of cyclin D family that promotes cell cycle progression to the DNA systhesis (S) phase. Cyclins ... Cyclin D3 regulates cell proliferation during hematopoiesis, carcinogenesis, and may have function in the terminally ... In recent studies, there is reports that cyclin D3 involves in multiple myeloma and malignant precursor T cells. Essential for ...
Through detecting Cyclin D3 expression in 243 breast cancer patients tissue array, we found Cyclin D3 expression was ... was significantly poor in high Cyclin D3 expression BC patients (p = 0.004). Furthermore, expression of Cyclin D3 was ... is a regulator of Cyclin-dependent kinases 4 and 6. Previous studies revealed that abnormal expression of Cyclin D3 was found ... qRT-PCR was used to detect the mRNA level of Cyclin D3 in BC tissues and BC cell lines. Transwell assay was used to examine the ...
... cyclinD3, Active Human Recombinant Protein \ 40096 for more molecular products just contact us ... Ccnd3 Cyl-3] G1/S-specific cyclin-D3. [CCND3] G1/S-specific cyclin-D3. [Cdk7 Cak Cdkn7 Crk4 Mo15 Mpk-7] Cyclin-dependent kinase ... Cdkn2a P16ink4a] Cyclin-dependent kinase inhibitor 2A (Cyclin-dependent kinase 4 inhibitor A) (CDK4I) (p16-INK4a) (p16-INK4). [ ... Cdkn2a P16ink4a] Cyclin-dependent kinase inhibitor 2A (Cyclin-dependent kinase 4 inhibitor A) (CDK4I) (p16-INK4a) (p16) (p16- ...
... of the mouse cyclin D3 gene, which encodes a G1 phase cyclin. The gene consists of five exons and four introns, varying in ... of the mouse cyclin D3 gene, which encodes a G1 phase cyclin. The gene consists of five exons and four introns, varying in ... of the mouse cyclin D3 gene, which encodes a G1 phase cyclin. The gene consists of five exons and four introns, varying in ... of the mouse cyclin D3 gene, which encodes a G1 phase cyclin. The gene consists of five exons and four introns, varying in ...
Cyclic AMP-dependent phosphorylation of cyclin D3-bound CDK4 determines the passage through the cell cycle restriction point in ... Cyclic AMP-dependent phosphorylation of cyclin D3-bound CDK4 determines the passage through the cell cycle restriction point in ... Immobilised cyclin-dependent kinase 4 fusion proteins and uses thereof par Raspé, Eric , Roger, Pierre P. , Coulonval, Katia , ...
... while the corresponding portion of pRb interacted with either cyclin D3 or cyclin D1. In T98G cells, endogenous cyclin D3- ... while the corresponding portion of pRb interacted with either cyclin D3 or cyclin D1. In T98G cells, endogenous cyclin D3- ... while the corresponding portion of pRb interacted with either cyclin D3 or cyclin D1. In T98G cells, endogenous cyclin D3- ... while the corresponding portion of pRb interacted with either cyclin D3 or cyclin D1. In T98G cells, endogenous cyclin D3- ...
Lack Of Cyclin D3 Induces Skeletal Muscle Fiber Type Shifting, with description: Lack of cyclin d3 induces skeletal muscle ... Lack Of Cyclin D3 Induces Skeletal Muscle Fiber Type Shifting. Feb 5th ...
... 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 ... D-type cyclins (cyclins D1, D2, and D3) are key components of cell cycle machinery in mammalian cells. These proteins are ... Moreover, induction of D-cyclins causes redistribution of p27Kip1 from cyclin E-CDK to cyclin D-CDK molecules (6). ...
  • Transcription of these particular cyclins is proposed to monitor the growth factor signal and the encoded proteins participate in G1 progression. (bl.uk)
  • Additionally we are shipping Cyclin D3 Kits (40) and Cyclin D3 Proteins (7) and many more products for this protein. (antibodies-online.com)
  • We also detected the proteins which interacted with Cyclin D3 to further elucidate the mechanism in Cyclin D3 mediated pathway in breast cancer. (biomedcentral.com)
  • CDK6_cyclinD3, Active Human Recombinant Protein recombinant proteins Most stable storage is at - 81 C or lower but some lyophilised proteins can be stored at +4C. (antibody-antibodies.com)
  • GENTAUR suppliers human normal cells, cell lines, RNA extracts and lots of antibodies and ELISA kits to Human proteins as well as CDK6_cyclinD3, Active Human Recombinant Protein. (antibody-antibodies.com)
  • Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. (wikipedia.org)
  • Cyclins are a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (Cdk) enzymes. (embl.de)
  • There are 14939 Cyclin_C domains in 14900 proteins in SMART's nrdb database. (embl.de)
  • Taxonomic distribution of proteins containing Cyclin_C domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with Cyclin_C domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing Cyclin_C domain in the selected taxonomic class. (embl.de)
  • In a series of experiments, lead author Nathalie M. Fiaschi-Taesch, Ph.D., assistant professor of endocrinology, and the team discovered that combining elevated amounts of the regulatory molecules cdk4 or cdk6 with a variety of D-cyclin proteins, particularly cyclin D3, stimulates human beta cell replication in test tubes. (upmc.com)
  • The western blotting results demonstrated that IDH1 R132H mutation decreased the expression levels of the S phase‑associated proteins Cyclin A and CDK2, and increased the expression levels of the G 1 phase‑associated proteins Cyclin D3 and CDK4, but did not significantly change the expression levels of the G 2 /M phase‑associated protein Cyclin B1. (spandidos-publications.com)
  • This gene encodes a proline-directed serine/threonine kinase that is a member of the cyclin-dependent kinase family of proteins. (genecards.org)
  • In humans, in addition to the mouse homologue, two more cyclin D proteins have been identified. (academic.ru)
  • These human proteins, called cyclin D1 , cyclin D2 , and cyclin D3 are expressed in most proliferating cells and the relative amounts expressed differs in various cell types. (academic.ru)
  • The activity of cdc2 was higher in infected cell lysates than those of corresponding proteins present in lysates of mock-infected cells even though cyclins A and B were not detectable in lysates of infected cells. (asm.org)
  • The experiments targeted two related proteins, cyclin D1 and cyclin D3, that control cells' growth cycle. (medindia.net)
  • Cyclin proteins act as "checkpoint" guards to control cell's cycle of rest, growth and division. (medindia.net)
  • To test these questions, Choi and her Dana-Farber colleagues developed a strain of mice with cyclin D proteins that could be inactivated at any time by treating the mice with the drug tamoxifen. (medindia.net)
  • When the cyclin D proteins were turned off using this technique, the addicted cancer cells shut down while normal cells were unaffected. (medindia.net)
  • Like Cyclin D1 and Cyclin D2, it is activated by the same mechanisms and can phosphorylate pRB when associated with cdk4 and cdk6. (thermofisher.com)
  • This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activtiy is required for cell cycle G1/S transition. (genetex.com)
  • Please read carefully the data sheet of the CDK6_cyclinD3, Active Human Recombinant Protein. (antibody-antibodies.com)
  • CDK6_cyclinD3, Active Human Recombinant Protein Human samples 80 % of the research is conducted on human samples. (antibody-antibodies.com)
  • While cyclin D3 expression contributes to cell-cycle progression in Notch-dependent human T-ALL cell lines, ectopic expression of CDK4 or CDK6 together with cyclin D3 shows partial rescue from 7-secretase inhibitor (GSI)-induced G 1 arrest in these cell lines. (elsevier.com)
  • The largest defect observed in c- myc −/− cells is a 12-fold reduction in the activity of cyclin D1-Cdk4 and -Cdk6 complexes during the G 0 -to-S transition. (asm.org)
  • Cyclin D1 or D3 expression does not vary in the clinical course, but that alone is insufficient to promote cell cycle progression unless cyclin-dependent kinase 4 (cdk4) is also elevated, in the absence of cdk6, to phosphorylate the retinoblastoma protein (Rb). (aacrjournals.org)
  • By contrast, cyclin D2 and cdk6 are coordinately increased, thereby overriding the inhibition by cdk inhibitors p18 INK4c and p27 Kip1 and phosphorylating Rb in conjunction with the existing cdk4. (aacrjournals.org)
  • Thus, cyclin D1 pairs exclusively with cdk4 and cdk6 pairs only with cyclin D2, although cyclin D2 can also pair with cdk4 in multiple myeloma cells. (aacrjournals.org)
  • In addition, cyclin D1- or cyclin D3-expressing multiple myeloma cells are uniformly distributed in the bone marrow, whereas cdk6-specific phosphorylation of Rb occurs in discrete foci of bone marrow multiple myeloma cells before proliferation early in the clinical course and is then heightened with proliferation and disease progression. (aacrjournals.org)
  • Mutually exclusive cdk4/cyclin D1 and cdk6/cyclin D2 pairing, therefore, is likely to be a critical determinant for cell cycle reentry and progression and may play a pivotal role in the expansion of self-renewing multiple myeloma cells. (aacrjournals.org)
  • It is required for cell cycle activation in response to physiologic signals, such as antigen ( 4 , 5 ), that lead to coordinated elevation of cyclin D2 and cdk4, and then cdk6 ( 6 ). (aacrjournals.org)
  • Thus, although neither cdk4 nor cdk6 is required for cell cycle progression or viability in mice ( 11 ), specific D cyclins, cdk4/6, and CKIs are required for B-cell physiologic functions, implying that perturbation of this balance is likely to underlie oncogenesis in the B lineage. (aacrjournals.org)
  • Overexpression of the five, alone or in combination, led to variable increases in human β-cell replication, with the cdk6/cyclin D3 combination being the most robust (15% versus 0.3% in control β-cells). (diabetesjournals.org)
  • A single molecule, cdk6, proved to be capable of driving human β-cell replication in vitro and enhancing human islet engraftment/proliferation in vivo, superior to normal islets and as effectively as the combination of cdk6 plus a D-cyclin. (diabetesjournals.org)
  • CONCLUSIONS Human β-cells contain abundant cdk4, cdk6, and cyclin D3, but variable amounts of cyclin D1. (diabetesjournals.org)
  • Unexpectedly, cyclin D3 and cdk6 overexpression drives human β-cell replication most effectively. (diabetesjournals.org)
  • Specifically, passage through G 1 requires the activities of D-type cyclins (D1, D2, D3) associated with Cdk4 or Cdk6, followed by activation of the cyclin E- and A-dependent kinase, Cdk2, as cells near the G 1 -S transition ( 79 ). (asm.org)
  • We didn't expect cyclin D3 to ramp up beta cell replication so strongly when it was used with either cdk4 or cdk6," Dr. Fiaschi-Taesch said. (upmc.com)
  • Cyclin D2 is present in and essential for rodent beta cell replication and function, but the team showed that molecule is barely detectable in human cells, and beta cell replication could be sustained for at least four weeks in a model in which mice were transplanted with human beta cells engineered to overproduce cdk6. (upmc.com)
  • Mice don't appear to make cdk6 naturally, but they do have cdk4 and cyclins D1 and D2, so standard rodent studies of beta replication might have led scientists to pursue the wrong molecules in their quest to stimulate human beta cell replication, Dr. Stewart noted. (upmc.com)
  • The BCH inhibited the expression of cyclin-dependent protein kinase 6 (CDK6) in a time-dependent manner. (biomedsearch.com)
  • These results suggest that, in KB cells, the inhibition of LAT1 by BCH causes cell cycle arrest at G1 phase by inhibiting cyclin D3-CDK6 complex whereas increasing expression of a CDK inhibitor p27. (biomedsearch.com)
  • 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)
  • [ 4 ] Viral cyclin D binds human Cdk6 and inhibits Rb by phosphorylating it, which subsequently inhibits expression of genes important for DNA synthesis. (academic.ru)
  • Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development. (umassmed.edu)
  • Amplification of chromosome band 11q13 and a role for cyclin D1 in human breast cancer. (semanticscholar.org)
  • There was no known role for cyclin D3 in human beta cell physiology. (upmc.com)
  • A role for cyclin D3 in the biology of HSV-1 emerged from mapping studies ( 44 ). (asm.org)
  • Cyclin D3 is a G1 cyclin closely related to Cyclins D1 and D2 phase progression. (thermofisher.com)
  • Kim, Kim, Ko: CKbeta8/CCL23 and its isoform CKbeta8-1 induce up-regulation of cyclins via the G(i)/G(o) protein/PLC/PKCdelta/ERK leading to cell-cycle progression. (antibodies-online.com)
  • The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. (genetex.com)
  • We report that cyclin D3 is rate limiting for G1 progression in thyroid follicular cells and that its constitutive upregulation by chronic stimulation of the TSH/cAMP pathway plays a role in human and experimental hyperproliferative diseases of the thyroid gland. (nih.gov)
  • Interference with the expression of G1 cyclins (in particular cyclin D3) by the antisense methodology strongly reduced TSH-dependent proliferation of PC Cl 3 cells, indicating that proper progression through G1 requires cyclin D3. (nih.gov)
  • Key target genes in this process include master regulators of the cell cycle, such as cyclin E, which regulates G(1) progression, and cyclin A, which is required for the initiation of DNA synthesis. (semanticscholar.org)
  • Cyclin D3, ~34kDa, is a member of cyclin D family that promotes cell cycle progression to the DNA systhesis (S) phase. (adipogen.com)
  • Therefore, abnormal expression of cyclins was reported to be involved in many cancers progression. (biomedcentral.com)
  • 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)
  • Thus, D-cyclins also control cell cycle progression in a kinase-independent manner, via their interaction with p27 Kip1 . (pnas.org)
  • However, the superinducibility and temporal shift of cyclin D3 by CHX suggest that there is a different regulatory mechanism underlying cyclin D1 and D3 gene expressions in the mouse uterine cell cycle progression. (elsevier.com)
  • 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)
  • Cyclin D is a member of the cyclin protein family that is involved in regulating cell cycle progression. (academic.ru)
  • In proliferating cells, cyclin D-Cdk4/6 complex accumulation is of great importance for cell cycle progression. (academic.ru)
  • Namely, cyclin D-Cdk4/6 complex partially phosphorylates Rb, which is able to induce expression of some genes (for example: cyclin E) important for S phase progression. (academic.ru)
  • In its un-phosphorylated form, Rb binds a member of E2F family of transcription factors which controls expression of several genes involved in cell cycle progression (example, cyclin E). Rb acts as a repressor, so in complex with E2F it prevents expression of E2F regulates genes, and this inhibits cells from progressing through G1. (academic.ru)
  • D-type cyclins and their complexing CDKs phosphorylate the retinoblastoma gene product with influences transcription of growth-controlling genes. (adipogen.com)
  • RESULTS Human β-cells contain easily detectable cdks 4 and 6 and cyclin D3 but variable cyclin D1. (diabetesjournals.org)
  • GATA-1 inhibited expression of cyclin-dependent kinase (Cdk) 6 and cyclin D2 and induced the Cdk inhibitors p18 INK4C and p27 Kip1 with associated inactivation of all G 1 Cdks. (asm.org)
  • 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)
  • 7 Regulation of the cell cycle of stem/progenitor cells by cyclins, cdks, and cdk inhibitors may contribute to proliferation and differentiation of various lineage cells. (bloodjournal.org)
  • I have been defining the cis -acting elements and trans -acting factors that control transcription of the human cyclin D3 gene in T-cells. (bl.uk)
  • 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. (bl.uk)
  • The human cyclin D3 gene has a TATA-less promoter and a single dominant initiation site. (bl.uk)
  • 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. (genetex.com)
  • We have determined the complete nucleotide sequence (-1681 to +6582) of the mouse cyclin D3 gene, which encodes a G1 phase cyclin. (elsevier.com)
  • The characterization of the mouse cyclin D3 gene and insight into its promoter region will allow further studies defining the molecular events regulating the expression of this cyclin in proliferating and quiescent cells. (elsevier.com)
  • The E 2 - induced cyclin D1 and D3 gene expressions were blocked by antiestrogens tamoxifen and ICI 182,780. (elsevier.com)
  • We also investigated the effects of cycloheximide (CHX), a protein synthesis inhibitor, on cyclin D1 and D3 gene expressions. (elsevier.com)
  • The E 2 -induced cyclin D3 gene expression was shifted by approximately 6 h when CHX was pretreated 1 hr before E 2 administration. (elsevier.com)
  • Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene . (wikipedia.org)
  • Functional characterization of a rare germline mutation in the gene encoding the cyclin-dependent kinase inhibitor p27Kip1 (CDKN1B) in a Spanish patient with multiple endocrine neoplasia-like phenotype. (curehunter.com)
  • CDK5 (Cyclin Dependent Kinase 5) is a Protein Coding gene. (genecards.org)
  • Wang Z, Zhang Y, Lu J, Sun S, and Ravid K. Mpl ligand enhances the transcription of the cyclin D3 gene: a potential role for Sp1 transcription factor. (hopkinsmedicine.org)
  • Active cyclin D/Cdk4 and -6 inhibit Rb by partial phosphorylation, reducing its binding to E2F and thereby allowing E2F-mediated activation of the transcription of the cyclin E gene and the cell progresses towards S-phase. (academic.ru)
  • vi) The decrease in the levels of cyclins A and B, the increase in activity of cdc2, and the hyperphosphorylation of cdc-25C were mediated by U L 13 and α22/U S 1.5 gene products. (asm.org)
  • Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. (abcam.com)
  • Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated to the nucleus through interaction with KIP/CIP family members. (abcam.com)
  • Bagui, Jackson, Agrawal, Pledger: Analysis of cyclin D3-cdk4 complexes in fibroblasts expressing and lacking p27(kip1) and p21(cip1). (antibodies-online.com)
  • 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)
  • [5] Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. (wikipedia.org)
  • Downstream events, such as activation of cyclin E-Cdk2 and cyclin A-Cdk2 complexes, are delayed and reduced in magnitude. (asm.org)
  • In exponentially cycling cells the absence of c-Myc reduces coordinately the activities of all cyclin-cyclin-dependent kinase complexes. (asm.org)
  • P27Kip1 and p21Cip1 are not required for the formation of active D cyclin-cdk4 complexes. (nih.gov)
  • In thisreview, we focus our attention on cyclin-cyclin-dependent kinase complexes,cyclin kinase inhibitors, genes of the retinoblastoma family, p53 and N-Myc, and we aim to summarize the latest evidence indicating their involvement in thecontrol of the cell cycle and induction of differentiation in different celltypes of the peripheral and central nervous systems. (embl.de)
  • Mammalian cyclin D-Cdk4 complexes have been characterized as growth factor‐responsive cell cycle regulators. (embopress.org)
  • In general, all stages of the cell cycle are chronologically separated in humans and are triggered by cyclin-Cdk complexes which are periodically expressed and partially redundant in function. (academic.ru)
  • Even though cyclin D levels in proliferating cells are sustained as long as the growth factors are present, a key player for G1/S transition is active cyclin D-Cdk4/6 complexes. (academic.ru)
  • Cell proliferation, differentiation, and fate are controlled by the cell cycle, which depends on a highly ordered formation and activation of cyclin-cyclin-dependent kinase (cdk) complexes. (bloodjournal.org)
  • 2-6 Cyclin E binds to and activates cdk2 protein kinase, and in proliferating cells the assembly of catalytically active cyclin E-cdk2 complexes is directly related to the abundance of cyclin E protein. (bloodjournal.org)
  • However, PTEN induced a specific reduction of cyclin D3 levels and an associated increase in the amount of the inhibitor p27 KIP1 complexed with CDK2. (aacrjournals.org)
  • NeoPalAna: Neoadjuvant Palbociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor, and Anastrozole for Clinical Stage 2 or 3 Estrogen Receptor-Positive Breast Cancer. (semanticscholar.org)
  • Consistent with accumulation of cells in G1/G0, 1,25 D treatment of LNCaP cells resulted in decreased retinoblastoma protein phosphorylation, repressed E2F transcriptional activity, increased levels of the cyclin-dependent kinase (CDK) inhibitor p21(WAF1, CIP1) and decreased CDK2 activity. (elsevier.com)
  • The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16 INK4a . (wikipedia.org)
  • It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18. (curehunter.com)
  • Apoptosis of osteosarcoma cultures by the combination of the cyclin-dependent kinase inhibitor SCH727965 and a heat shock protein 90 inhibitor. (nih.gov)
  • Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer. (curehunter.com)
  • The treatment of quiescent cells with growth factors results in the transcriptional activation of the D-type cyclin genes during G1. (bl.uk)
  • Comparison of these results with those for the cyclin D1 and D2 genes should elucidate how transcription of these genes is co-ordinately regulated by growth factors. (bl.uk)
  • Cyclin C was originally identified by a genetic screen for human and Drosophila cDNAs that complement a triple knock-out of the CLN genes in Saccharomyces cerevisiae. (novusbio.com)
  • Colony formation experiments were used to detect cell proliferation in each group, cell cycle distribution was detected by flow cytometry and western blotting was used to detect the expression levels of wild‑type and mutant IDH1, cyclins, biological rhythm genes and Smad signaling pathway‑associated genes in U87‑MG cells. (spandidos-publications.com)
  • One of the members of the pathways, MAPK activates a transcription factor Myc, which alters transcription of genes important in cell cycle, among which is cyclin D. In this way, cyclin D is synthesized as long as the growth factor is present. (academic.ru)
  • This cell cycle arrest correlated with an inability to increase cyclin D3 expression resulting from a decreased mRNA stability and an impaired translation. (jimmunol.org)
  • We sought to determine the mechanisms leading to a decreased cyclin D3 mRNA stability in activated T cells cultured in medium deprived of L-Arg. (jimmunol.org)
  • Results show that cyclin D3 mRNA instability induced by L-Arg deprivation is dependent on response elements found in its 3′-untranslated region (UTR). (jimmunol.org)
  • RNA-binding protein HuR was found to be increased in T cells cultured in medium with L-Arg and bound to the 3′-untranslated region of cyclin D3 mRNA in vitro and endogenously in activated T cells. (jimmunol.org)
  • Silencing of HuR expression significantly impaired cyclin D3 mRNA stability. (jimmunol.org)
  • This was the result of a decreased cyclin D3 mRNA stability and a diminished cyclin D3 translation. (jimmunol.org)
  • However, the mechanisms to explain the decrease in cyclin D3 mRNA stability induced by L-Arg starvation are still unknown. (jimmunol.org)
  • Results shown in this study demonstrate that the decrease in cyclin D3 mRNA stability induced by L-Arg deprivation is dependent on elements within the 3′-UTR of the cyclin D3 mRNA. (jimmunol.org)
  • The RBP HuR binds to the cyclin D3 mRNA in vitro and endogenously in activated T cells cultured with L-Arg, but not in L-Arg-deprived T cells. (jimmunol.org)
  • qRT-PCR was used to detect the mRNA level of Cyclin D3 in BC tissues and BC cell lines. (biomedcentral.com)
  • Promoter activity was high in cell lines that expressed high levels of endogenous D3 mRNA, as indicated by Northern blot analyses, and was significantly reduced when the promoter was truncated to -122 bp. (elsevier.com)
  • Time-course changes in cyclin D1 and D3 mRNA levels in the uterine tissues of immature mice primed with 17β- estradiol (E 2 ) were examined by Northern blot hybridization. (elsevier.com)
  • Cyclin D1 and D3 mRNAs were induced 2.5-fold between c-fos and TK mRNA peaks. (elsevier.com)
  • When CHX was treated alone, cyclin D3, but not cyclin D1, mRNA was immediately superinduced. (elsevier.com)
  • Overexpression of cyclin D3 accelerates the translocation whereas substitution of D199 with alanine abolishes the interaction with cyclin D3 and results in the retention of ICP0 in the nucleus ( , 11 ). (pnas.org)
  • Overexpression of cyclin D3 or survivin reverses the effects of miR-195 in NSCLC cells. (uthscsa.edu)
  • Zhang Y, Wang Z, Ravid K. The cell cycle in polyploid megakaryocytes is associated with reduced activity of cyclin B1-dependent cdc2 kinase. (hopkinsmedicine.org)
  • It is well known that the cell division of eukaryotes is regulated by a complex with a maturation promoting factor (MPF or Cdc2-cyclin B complex). (rupress.org)
  • Therefore, polyploidization of megakaryocytes has been postulated to be caused by either reduction of cyclin B and/or Cdc2 or diminished kinase activity of the complex. (rupress.org)
  • The cdk-1/cdc2 and cdk-2 and cyclin A and E family. (diabetesjournals.org)
  • In uninfected cells the G 2 /M transition is regulated by cyclin kinase complex containing cdc2 and, initially, cyclin A, followed by cyclin B. cdc2 is downregulated through phosphorylation by wee-1 and myt-1 and upregulated by cdc-25C phosphatase. (asm.org)
  • In rat thyrocytes (PC Cl 3 cells), cyclin D3 expression is enhanced in response to activation of the TSH/cAMP pathway. (nih.gov)
  • Accordingly, PC Cl 3 cells engineered to overexpress cyclin D3 (PC-D3 cells) show enhanced growth rate and elude hormone-dependence and contact inhibition. (nih.gov)
  • Using an animal experimental model of thyroid stimulation, we demonstrate that cyclin D3 is a key mediator of TSH-dependent proliferation of thyroid follicular cells also in vivo. (nih.gov)
  • Although PTEN signaling directly regulates p27 KIP1 levels in some settings, in endometrial carcinoma cells, PTEN expression indirectly regulated p27 KIP1 activity by modulating levels of cyclin D3. (aacrjournals.org)
  • The G 0 -G 1 arrest in the cell cycle observed in T cells cultured in L-Arg-deprived medium correlated with an inability to upregulate the expression of cyclin D3 ( 8 ). (jimmunol.org)
  • By using Jurkat cells as a model system, we have been able to demonstrate that cyclin D3 is reduced at the level of translation by inhibition of elongation. (nih.gov)
  • Taken together, it appears that activation of PKA in Jurkat cells reduces the expression of cyclin D3 at the level of translational elongation by increasing the phosphorylation of eEF2 and thereby inhibiting its activity. (nih.gov)
  • Early Cycling-independent Changes to p27, Cyclin D2, and Cyclin D3 in Differentiating Mouse Embryonal Carcinoma Cells -- Preclíková et al. (aacrjournals.org)
  • Cells lacking IKKα show nuclear cyclin D1 overexpression and a neoplastic phenotype: role of IKKα as a tumor suppressor. (semanticscholar.org)
  • Cyclin D3 regulates cell proliferation during hematopoiesis, carcinogenesis, and may have function in the terminally differentiated cells. (adipogen.com)
  • In recent studies, there is reports that cyclin D3 involves in multiple myeloma and malignant precursor T cells. (adipogen.com)
  • Transwell assay was used to examine the role of Cyclin D3 in the migration and invasion of BC cells. (biomedcentral.com)
  • Further investigation showed Cyclin D3 was involved in the metastasis of BC cells and physically interacted with actin in vivo and in vitro. (biomedcentral.com)
  • Cyclin D3 was widely expressed in many tumor cells. (biomedcentral.com)
  • Rapamycin causes a G1 arrest in HER-2-overexpressing breast cancer cells that is associated with a differential destabilization and subsequent down-regulation of Cyclin D3 protein level [ 9 ]. (biomedcentral.com)
  • 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. (elsevier.com)
  • In T98G cells, endogenous cyclin D3-associated kinase activity showed a clear predisposition to phosphorylate preferentially the C-terminal domain of pRb2/p130, rather than that of pRb. (elsevier.com)
  • This propensity was also confirmed in LAN-5 human neuroblastoma cells, where phosphorylation of the pRb2/p130 C-terminal domain and expression of cyclin D3 also decreased remarkably in the late neural differentiation stages. (elsevier.com)
  • D-type cyclins (cyclins D1, D2, and D3) are key components of cell cycle machinery in mammalian cells. (pnas.org)
  • We demonstrated that miR-195 targets cyclin D3 to cause cell cycle arrest at the G1 phase and that miR-195 targets survivin to induce apoptosis and senescence in NSCLC cells. (uthscsa.edu)
  • An analysis of cyclin-dependent kinase complex regulators revealed increased expression of p27 KIP1 and decreased expression of Cdk7 in c- myc −/− cells. (asm.org)
  • Cyclin D2, in particular, is the major D cyclin expressed in mature B cells, the precursors of antibody secreting plasma cells. (aacrjournals.org)
  • In contrast to rodent β-cells, they contain little or no detectable cyclin D2. (diabetesjournals.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)
  • Similarly, in the developing midbrain-hindbrain region the D-type cyclins were expressed in different subsets of cells. (scielo.br)
  • G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). (embl.de)
  • During these rounds of replication, cytokinesis is neglected because of the down-regulated expression of AIM-1, and DNA replication occurs through the increased expression of D-type cyclins.As for transcriptional regulation during megakary-opoiesis, GATA-1 plays a central role in the lineage commitment of hematopoietic stem cells toward erythroid/megakaryocytic lineage and subsequent maturation. (springer.com)
  • The bottom left panel shows induction of pRb phosphorylation in INS1 cells that have been transduced with the combination of the adenoviruses Ad.cdk4 plus Ad.cyclin D1. (diabetesjournals.org)
  • Thus, substitution of aspartic acid 199 with alanine in ICP0 abolished stabilization of cyclin D3, reduced the yields of virus from resting cells, and reduced the capacity of the virus to invade the mouse central nervous system from a peripheral site. (asm.org)
  • Blocking cyclin D1 in the mice drove the breast cancer cells into a kind of permanent retirement called senescence, an irreversible halt to their growth cycle. (medindia.net)
  • Inhibiting cyclin D3 in the T-ALL leukemia mice caused the cancer cells to self-destruct -- a programmed death process called apoptosis. (medindia.net)
  • In addition to these tests with mouse cancers, the scientists found that the cyclin-D-inhibiting drug had similar effects on human blood cancer cells in the laboratory. (medindia.net)
  • The D-cyclins determine when a cell begins making DNA in preparation for dividing to form new cells. (medindia.net)
  • In many types of cancer, an excess of cyclins allows cells to grow too fast and form tumors. (medindia.net)
  • Also unknown was whether normal cells could get along without cyclin D1: If not, treating cancer by targeting the protein might be too dangerous. (medindia.net)
  • The authors say the results show that blocking cyclin D "represents a highly selective anticancer strategy that specifically targets cancer cells without significantly affecting normal tissues. (medindia.net)
  • abstract = "The three D-type cyclins have been shown to be differentially expressed in a number of cell types, suggesting that they play distinct roles in cell cycle regulation in particular cell lineages. (elsevier.com)
  • abstract = "An association between cyclin D3 and the C-terminal domain of pRb2/p130 was demonstrated using the yeast two-hybrid system. (elsevier.com)
  • abstract = "D-type cyclins are involved in the regulation of the G1/S transition of the cell cycle in various cell types cultured in vitro. (elsevier.com)
  • 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)
  • Due to this property of D-cyclins, they are regarded as mitogenic sensors that relay signals from the extracellular environment to the core cell cycle machinery ( Sherr and Roberts, 1999 ). (pubmedcentralcanada.ca)
  • Synthetic peptide corresponding to Human Cyclin D3 (phospho T283) conjugated to Keyhole Limpet Haemocyanin (KLH). (abcam.com)
  • Bartkova, Zemanova, Bartek: Abundance and subcellular localisation of cyclin D3 in human tumours. (antibodies-online.com)
  • Recombinant protein encompassing a sequence within the center region of human Cyclin D3. (genetex.com)
  • Finally, we found that cyclin D3 protein is expressed in a fraction of human goiters but it is strongly overexpressed in most follicular adenomas. (nih.gov)
  • Cyclin D1 and prognosis in human breast cancer. (semanticscholar.org)
  • Genomic changes disrupting the expression of Cyclin D3 are associated with aberrant growth of several human B-lymphoid malignancies [ 4 ]. (biomedcentral.com)
  • Previous studies showed that Cyclin D1 and D3 are overexpressed in human breast cancer cell lines and primary invasive breast cancers and Cyclin D3 frequently exceeded the expression of Cyclin D1 in ErbB2-positive cases [ 1 ]. (biomedcentral.com)
  • 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)
  • Importantly, cyclin D3 and CDK4 are highly overexpressed in Notch-dependent T-cell lymphomas, justifying the combined use of cell-cycle inhibitors and GSI in treating human T-cell malignancies. (elsevier.com)
  • Zhuang, SH & Burnstein, KL 1998, ' Antiproliferative effect of 1α,25-dihydroxyvitamin D 3 in human prostate cancer cell line LNCaP involves reduction of cyclin-dependent kinase 2 activity and persistent G1 accumulation ', Endocrinology , vol. 139, no. 3, pp. 1197-1207. (elsevier.com)
  • Human cdk8-cyclin C might be functionally associated with the mammalian transcription apparatus, perhaps involved in relaying growth-regulatory signals. (novusbio.com)
  • We explored the presence, subcellular localization, and function of five early G1/S phase molecules-cyclins D1-3 and cdk 4 and 6-in the adult human β-cell. (diabetesjournals.org)
  • Cyclin homologues have been found in various viruses, including Saimiriine herpesvirus 2 (Herpesvirus saimiri) and Human herpesvirus 8 (HHV-8) (Kaposi's sarcoma-associated herpesvirus). (embl.de)
  • 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)
  • Crystal structure of human cyclin D1 (blue/green) in complex with cyclin-dependent kinase 4 (yellow/red). (academic.ru)
  • In viruses, like Saimiriine herpesvirus 2 ( Herpesvirus saimiri ) and Human herpesvirus 8 ( HHV-8 / Kaposi's sarcoma-associated herpesvirus ) cyclin D homologues have acquired new functions in order to manipulate the host cell's metabolism to the virus' benefit. (academic.ru)
  • Furthermore, inhibition of eEF2-kinase prevented the forskolin-mediated down-regulation of cyclin D3. (nih.gov)
  • Inhibition of cysteine proteinases and proteosome by Ras, Ran and cyclin. (nii.ac.jp)
  • Inhibition of GSK3β in both DM1 cell culture and mouse models corrected cyclin D3 levels and reduced muscle weakness and myotonia in DM1 mice. (jci.org)
  • The minimal cyclin D3 promoter sequence was identified as a region 173bp upstream of the transcription initiation site. (bl.uk)
  • 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)
  • The expression of cyclins D1 and D3 was examined during estradiol-17beta (E(2))-induced mammary tumorigenesis in female August Copenhagen Irish (ACI) rats. (semanticscholar.org)
  • Regulatory component of the cyclin D3-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. (abcam.com)
  • Subsequently, cyclin E fully phosphorylates Rb and completes its inactivation. (academic.ru)
  • The immunogen for the anti-h-Cyclin D3 was a recombinant full length Cyclin D3 protein recognizing a 34 kD protein. (thermofisher.com)
  • Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (abcam.com)
  • Western blotting showed activation of ATF2 and HSP27 (substrates of p38 MAPK), and upregulation of cyclin D and downregulation of p27 were induced by inhibiting p38 MAPK. (arvojournals.org)
  • One of the best known substrates of cyclin D/Cdk4 and -6 is the retinoblastoma tumor suppressor protein ( Rb ). (academic.ru)
  • The studies described in this report stemmed from the observation that the infected cell protein No.0 (ICP0) of herpes simplex virus 1 (HSV-1) binds to and stabilizes cyclin D3 ( 18 ). (asm.org)
  • Accumulation of p27(kip1) is associated with cyclin D3 overexpression in the oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma," Journal of Clinical Pathology , vol. 60, no. 4, pp. 377-381, 2007. (hindawi.com)
  • In addition, D-cyclins play a kinase-independent role by sequestering cell cycle inhibitors p27 Kip1 and p21 Cip1 . (pnas.org)
  • To test the significance of cyclin D1-p27 Kip1 interaction within a living mouse, we crossed cyclin D1-deficient mice with mice lacking p27 Kip1 , and we generated double-mutant cyclin D1 −/− p27 −/− animals. (pnas.org)
  • Here we report that ablation of p27 Kip1 restores essentially normal development in cyclin D1-deficient mice. (pnas.org)
  • Our results provide genetic evidence that p27 Kip1 functions downstream of cyclin D1. (pnas.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 crossed cyclin D1-deficient mice with mice lacking p27 Kip1 ( 9 - 11 ) and generated double-mutant animals. (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)
  • Accumulation of p27(kip1) is associated with cyclin D3 overexpression in the oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma. (medscape.com)
  • The synthesis of cyclin D is initiated during G1 and drives the G1/S phase transition. (academic.ru)
  • Previous studies revealed that abnormal expression of Cyclin D3 was found in many different cancers. (biomedcentral.com)
  • 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)
  • 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)
  • Although cyclin D1 overexpression is clearly implicated in the affected cancers, overexpression of cyclin D1 is not sufficient to drive oncogenic transformation. (pubmedcentralcanada.ca)
  • Abnormal cyclins D1, D2 and D3 are found in breast, lung, endometrial, pancreatic, and testicular cancers and in multiple myeloma and other blood cancers. (medindia.net)
  • The INK4 family of CKIs (p16, p15, p18, and p19) inhibits cdk4/6 and the Cip/Kip family of CKIs (p21, p27, and p57) inhibits cyclin E/cdk 2. (aacrjournals.org)
  • The overall results suggest that both cyclin D1 and D3 mRNAs are constitutively expressed in uterine tissues and induced by E 2 at G 1 phase of the mouse uterine cell cycle. (elsevier.com)
  • Cyclin D3 was moderately up-regulated during the proliferation phase, and both cyclin E and D3 were rapidly down-regulated during terminal differentiation. (bloodjournal.org)
  • transition from G2 to M phase is initiated by the mitotic cdk complex composed of cyclin B and p34cdc2. (bloodjournal.org)
  • 1 G1 cyclins, such as cyclin D and E, play crucial roles as rate-limiting activators in G1/S phase transition. (bloodjournal.org)
  • Little is, however, known about the expression pattern and functional role of D-type cyclins in physiological processes in vivo. (elsevier.com)
  • In this report, we studied whether the expression of murine D-type cyclins correlates with the states of mouse uterine cell proliferation in vivo. (elsevier.com)
  • Here we characterize the in vivo function of Drosophila Cyclin D (CycD). (embopress.org)
  • In the past, we and others generated cyclin D1-deficient mice and have shown that these mice display developmental abnormalities, hypoplastic retinas, and pregnancy-insensitive mammary glands. (pnas.org)
  • We took advantage of cyclin D1-deficient mice that we and others had previously generated. (pnas.org)
  • These cyclin D1 −/− mice are viable but show developmental abnormalities and hypoplastic retinas and display mammary glands that fail to undergo normal lobuloalveolar development during pregnancy ( 7 , 8 ). (pnas.org)
  • Generation of Double-Mutant Cyclin D1 −/− p27 −/− Mice. (pnas.org)
  • Cyclin D1 +/− mice ( 7 , 8 ) were crossed with p27 +/− ( 11 ) mice. (pnas.org)
  • The resulting cyclin D1 +/− p27 +/− heterozygotes were bred to generate cyclin D1 −/− p27 −/− mice. (pnas.org)
  • A ) Levels of total GSK3α, GSK3β, cyclin D3, and actin were determined by Western blot analyses of total protein extracts from skeletal muscle (soleus) of HSA LR mice (at 6 months of age) and extracts from matching WT mice. (jci.org)
  • Mice, Drosophila and many other organisms only have one cyclin D protein. (academic.ru)
  • In a key report in Nature in 2001, Sicinski showed that mice engineered to lack cyclin D1 were resistant to developing breast cancer. (medindia.net)
  • Enforced expression of cyclin D3 abrogated the PTEN-induced cell cycle arrest. (aacrjournals.org)
  • The arrest in cyclin D3 protein synthesis by L-Arg deprivation was triggered by the general control nonderepressible 2 (GCN2) kinase ( 8 ) and the subsequent phosphorylation of eukaryotic translation initiation factor 2 (eIF2)α ( 9 ). (jimmunol.org)