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.

Transcriptional regulation of the cyclin D1 promoter by STAT5: its involvement in cytokine-dependent growth of hematopoietic cells. (1/369)

STAT5 is a member of a family of transcription factors that participate in the signal transduction pathways of many hormones and cytokines. Although STAT5 is suggested to play a crucial role in the biological effects of cytokines, its downstream target(s) associated with cell growth control is largely unknown. In a human interleukin-3 (IL-3)-dependent cell line F-36P-mpl, the induced expression of dominant-negative (dn)-STAT5 and of dn-ras led to inhibition of IL-3-dependent cell growth, accompanying the reduced expression of cyclin D1 mRNA. Also, both constitutively active forms of STAT5A (1*6-STAT5A) and ras (H-rasG12V) enabled F-36P-mpl cells to proliferate without added growth factors. In NIH 3T3 cells, 1*6-STAT5A and H-rasG12V individually and cooperatively transactivated the cyclin D1 promoter in luciferase assays. Both dn-STAT5 and dn-ras suppressed IL-3-induced cyclin D1 promoter activities in F-36P-mpl cells. Using a series of mutant cyclin D1 promoters, 1*6-STAT5A was found to transactivate the cyclin D1 promoter through the potential STAT-binding sequence at -481 bp. In electrophoretic mobility shift assays, STAT5 bound to the element in response to IL-3. Furthermore, the inhibitory effect of dn-STAT5 on IL-3-dependent growth was restored by expression of cyclin D1. Thus STAT5, in addition to ras signaling, appears to mediate transcriptional regulation of cyclin D1, thereby contributing to cytokine-dependent growth of hematopoietic cells.  (+info)

Cerebellar histogenesis is disturbed in mice lacking cyclin D2. (2/369)

Formation of brain requires deftly balancing primary genesis of neurons and glia, detection of when sufficient cells of each type have been produced, shutdown of proliferation and removal of excess cells. The region and cell type-specific expression of cell cycle regulatory proteins, such as demonstrated for cyclin D2, may contribute to these processes. If so, regional brain development should be affected by alteration of cyclin expression. To test this hypothesis, the representation of specific cell types was examined in the cerebellum of animals lacking cyclin D2. The loss of this cyclin primarily affected two neuronal populations: granule cell number was reduced and stellate interneurons were nearly absent. Differences between null and wild-type siblings were obvious by the second postnatal week. Decreases in granule cell number arose from both reduction in primary neurogenesis and increase in apoptosis of cells that fail to differentiate. The dearth of stellate cells in the molecular layer indicates that emergence of this subpopulation requires cyclin D2 expression. Surprisingly, Golgi and basket interneurons, thought to originate from the same precursor pool as stellate cells, appear unaffected. These results suggest that cyclin D2 is required in cerebellum not only for proliferation of the granule cell precursors but also for proper differentiation of granule and stellate interneurons.  (+info)

FLI-1 inhibits differentiation and induces proliferation of primary erythroblasts. (3/369)

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)

The proto-oncogene c-myc is a direct target gene of Epstein-Barr virus nuclear antigen 2. (4/369)

Epstein-Barr virus (EBV) infects and transforms primary B lymphocytes in vitro. Viral infection initiates the cell cycle entry of the resting B lymphocytes. The maintenance of proliferation in the infected cells is strictly dependent on functional EBNA2. We have recently developed a conditional immortalization system for EBV by rendering the function of EBNA2, and thus proliferation of the immortalized cells, dependent on estrogen. This cellular system was used to identify early events preceding induction of proliferation. We show that LMP1 and c-myc are directly activated by EBNA2, indicating that all cellular factors essential for induction of these genes by EBNA2 are present in the resting cells. In contrast, induction of the cell cycle regulators cyclin D2 and cdk4 are secondary events, which require de novo protein synthesis.  (+info)

Control of cell cycle entry and apoptosis in B lymphocytes infected by Epstein-Barr virus. (5/369)

Infection of human B cells with Epstein-Barr virus (EBV) results in activation of the cell cycle and cell growth. To interpret the mechanisms by which EBV activates the cell, we have assayed many proteins involved in control of the G0 and G1 phases of the cell cycle and regulation of apoptosis. In EBV infection most of the changes, including the early induction of cyclin D2, are dependent on expression of EBV genes, but an alteration in the E2F-4 profile was partly independent of viral gene expression, presumably occurring in response to signal transduction activated when the virus binds to its receptor, CD21. By comparing the expression of genes controlling apoptosis, including those encoding several members of the BCL-2 family of proteins, the known relative resistance of EBV-immortalized B-cell lines to apoptosis induced by low serum was found to correlate with expression of both BCL-2 and A20. A20 can be regulated by the NF-kappaB transcription factor, which is known to be activated by the EBV LMP-1 protein. Quantitative assays demonstrated a direct temporal relationship between LMP-1 protein levels and active NF-kappaB during the time course of infection.  (+info)

Early induction of cyclin D2 expression in phorbol ester-responsive B-1 lymphocytes. (6/369)

B-1 lymphocytes represent a distinct B cell subset with characteristic features that include self-renewing capacity and unusual mitogenic responses. B-1 cells differ from conventional B cells in terms of the consequences of phorbol ester treatment: B-1 cells rapidly enter S phase in response to phorbol ester alone, whereas B-2 cells require a calcium ionophore in addition to phorbol ester to trigger cell cycle progression. To address the mechanism underlying the varied proliferative responses of B-1 and B-2 cells, we evaluated the expression and activity of the G1 cell cycle regulator, cyclin D2, and its associated cyclin-dependent kinases (Cdks). Cyclin D2 expression was upregulated rapidly, within 2-4 h, in phorbol ester-stimulated B-1 cells, in a manner dependent on intact transcription/translation, but was not increased in phorbol ester- stimulated B-2 cells. Phorbol ester-stimulated cyclin D2 expression was accompanied by the formation of cyclin D2-Cdk4, and, to a lesser extent, cyclin D2-Cdk6, complexes; cyclin D2- containing complexes were found to be catalytically functional, in terms of their ability to phosphorylate exogenous Rb in vitro and to specifically phosphorylate endogenous Rb on serine780 in vivo. These results strongly suggest that the rapid induction of cyclin D2 by a normally nonmitogenic phorbol ester stimulus is responsible for B-1 cell progression through G1 phase. The ease and rapidity with which cyclin D2 responds in B-1 cells may contribute to the proliferative features of this subset.  (+info)

Involvement of p21(WAF1/Cip1) and p27(Kip1) in intestinal epithelial cell differentiation. (7/369)

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)

Molecular analysis of selected cell cycle regulatory proteins during aerobic and hypoxic maintenance of human ovarian carcinoma cells. (8/369)

We have previously reported on the development of an in vitro model system for studying the effect of hypoxia on ovarian carcinoma cell proliferation and invasion (Krtolica and Ludlow, 1996). These data indicate that the cell division cycle is reversibly arrested during the G1 phase. Here, we have continued this study to include the proliferation properties of both aerobic and hypoxic human ovarian carcinoma cells at the molecular level. The growth suppressor product of the retinoblastoma susceptibility gene, pRB, appears to be functional in these cells as determined by SV40 T-antigen binding studies. Additional G1-to-S cell cycle regulatory proteins, cyclins D and E, cyclin-dependent kinases (cdks) 4 and 2, and cdk inhibitors p27 and p18, also appear to be intact based on their apparent molecular weights and cell cycle stage-specific abundance. During hypoxia, there is a decrease in abundance of cyclins D and E, with an increase in p27 abundance. cdk4 activity towards pRB and cdk2 activity towards histone H1 are also decreased. Co-precipitation studies revealed an increased amount of p27 complexing with cyclin E-cdk2 during hypoxia than during aerobic cell growth. In addition, pRB-directed phosphatase activity was found to be greater in hypoxic than aerobic cells. Taken together, a model is suggested to explain hypoxia-induced cell cycle arrest in SKA human ovarian carcinoma cells.  (+info)

The future promises to yield new discoveries and advances in our understanding of cardiomyocyte cell cycle regulation that will hopefully give rise to the ability to promote regenerative myocardial growth. With respect to the intrinsic proliferative and de novo cardiomyogenic potential of the adult heart, it is abundantly clear from studies cited herein that the published values for the magnitude of both processes vary dramatically. It is very important to rigorously determine the extent to which these processes do occur. If the intrinsic rates for cardiomyocyte proliferation and/or de novo cardiomyogenic differentiation are exceedingly low, then the ability to exploit these processes for clinical benefit would likely be quite limited. Increasing the frequency of these events would require the existence, identification, and ultimately the successful delivery of cytokines that normally regulate the process. Conversely, if these processes do occur at the frequency that some studies suggest, then ...
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TY - JOUR. T1 - Cyclin D1 is not an immediate target of beta-catenin following Apc loss in the intestine.. AU - Sansom, O.J.. AU - Reed, K.R.. AU - Wetering, M.van de. AU - Muncan, V.. AU - Winston, D.. AU - Clevers, J.C.. AU - Clarke, A.R.. N1 - doi: 10.1074/jbc.M500191200. PY - 2005. Y1 - 2005. N2 - Cyclin D1 is postulated to be a target of the canonical Wnt pathway and critical for intestinal adenoma development. We show here that, unlike cyclin D1 reporter assays, endogenous cyclin D1 levels are not affected following antagonism of the Wnt pathway in vitro, nor is cyclin D1immediately up-regulated following conditional loss of Apc in vivo. Cyclin D1 levels do, however, increase in a delayed manner in a small subset of cells, suggesting such up-regulation occurs as a secondary event. We also analyzed the immediate consequences of Apc loss in a cyclin D1(-/-) background and failed to find any cyclin D1-dependent phenotypes. However, we did observe elevated cyclin D1 expression in lesions ...
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
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Cyclin D1 is a target for positive regulation by estrogens in growth-responsive cells, in which it mediates their mitogenic effects. Amplification and overexpression of the cyclin D1 gene (CCND1) might thus represent a genetic lesion inducing hormone-independent growth of transformed cells. Indeed, cyclin D1 overexpression has been found in up to 50% of primary breast cancers, and in about one-third of these cases, this is linked to amplification of the 11q13 chromosomal region, which also includes the CCND1 gene. These tumors are predominantly estrogen receptor-positive, and for this reason, these patients are often selected for adjuvant antiestrogen therapy. No information is available, however, as to whether cyclin D1 overexpression due to gene amplification might interfere with and reduce antiestrogen efficacy. This was investigated here by taking advantage of an experimental model that reproduces cyclin D1 overexpression resulting from increased CCND1 gene dosage in hormone-responsive human ...
THE 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.
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 ...
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, ...
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 ...
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...
...(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 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 ...
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 ...
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 ...
Cyclin D1 is a G1-specific cyclin that has been linked to lymphoid, parathyroid, and breast tumors. Recent studies suggested that high protein levels of cyclin D1 are not always produced when cyclin D1 mRNA is overexpressed in transfected cells, suggesting that posttranscriptional events may be important in cyclin D1 regulation. The mRNA cap-binding protein (eukaryotic initiation factor 4E [eIF-4E]) is a potential regulatory of several posttranscriptional events, and it can itself induce neoplastic transformation. Consequently, we examined eIF-4E as a potential regulator of cyclin D1. Overexpression of cyclin D1 mRNA in NIH 3T3 cells did not increase cyclin D1 protein. In contrast, overexpression of eIF-4E markedly increased the amount of cyclin D1 protein in NIH 3T3 cells. This increase was specific to cyclin D1 in comparison with the retinoblastoma gene product, c-Myc, actin, and eukaryotic initiation factor 2 alpha. We also examined cyclin D1 protein in cells expressing an estrogen ...
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
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 ...
Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest. Hudson, J., Mills, R., Titmarsh, D., Koenig, X., Parker, B., Ryall, J., Quaife-Ryan, G., Voges, H., Hodson, M., Ferguson, C., Drowley, L., Plowright, A., Wang, Q., Gregorevic, P., Xin, M., Thomas, W., Parton, R., Nielsen, L., Launikonis, B., James, D., Elliott, D. and Porrello, E. (2017). Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest. Abstracts for the 65th Cardiac Society of Australia and New Zealand Annual Scientific Meeting and the International Society for Heart Research Australasian Section Annual Scientific Meeting, Perth, Australia, 10 - 13 August 2017. Chatswood, NSW, Australia: Elsevier. doi: 10.1016/j.hlc.2017.06.375. ...
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.. ...
Aberrant expression of cyclin D1, frequently observed in human malignant disorders, has been linked to the control of G1→S cell cycle phase transition and development and progression in carcinogenesis. Cyclin D1 level changes are partially controlled by GSK-3β-dependent phosphorylation at threonine-286 (Thr286), which targets cyclin D1 for ubiquitination and proteolytic degradation. In our continuing studies on the mechanism of prostate cancer prevention by resveratrol, focusing on the role of its recently discovered target protein, quinone reductase 2 (NQO2), we generated NQO2 knockdown CWR22Rv1 using short hairpin RNA (shRNA)-mediated gene silencing approach. We found that, compared with cells expressing NQO2 (shRNA08), NQO2 knockdown cells (shRNA25) displayed slower proliferation and G1 phase cell accumulation. Immunoblot analyses revealed a significant decrease in phosphorylation of retinoblastoma Rb and cyclin D1 in shRNA25 compared with shRNA08. Moreover, shRNA25 cells showed a 37% ...
TY - JOUR. T1 - Cell-cycle-based strategies to drive myocardial repair. AU - Zhu, Wuqiang. AU - Hassink, Rutger J.. AU - Rubart, Michael. AU - Field, Loren J.. N1 - Copyright: Copyright 2009 Elsevier B.V., All rights reserved.. PY - 2009/7. Y1 - 2009/7. N2 - Cardiomyocytes exhibit robust proliferative activity during development. After birth, cardiomyocyte proliferation is markedly reduced. Consequently, regenerative growth in the postnatal heart via cardiomyocyte proliferation (and, by inference, proliferation of stem-cell-derived cardiomyocytes) is limited and often insufficient to affect repair following injury. Here, we review studies wherein cardiomyocyte cell cycle proliferation was induced via targeted expression of cyclin D2 in postnatal hearts. Cyclin D2 expression resulted in a greater than 500-fold increase in cell cycle activity in transgenic mice as compared to their nontransgenic siblings. Induced cell cycle activity resulted in infarct regression and concomitant improvement in ...
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. ...
Description: Description of target: Periostin, also known as OSF2, is a protein that in humans is encoded by the POSTN gene. The International Radiation Hybrid Mapping Consortium mapped the POSTN gene to chromosome 13. Periostin functions as a ligand for alpha-V/beta-3 and alpha-V/beta-5 integrins to support adhesion and migration of epithelial cells. It is found that periostin was overexpressed by the majority of human primary breast cancers examined. After myocardial infarction, periostin-induced cardiomyocyte cell cycle reentry and mitosis were associated with improved ventricular remodeling and myocardial function, reduced fibrosis and infarct size, and increase angiogenesis.;Species reactivity: Human;Application: ELISA;Assay info: Assay Methodology: Quantitative Sandwich Immunoassay;Sensitivity:
Cell proliferation is regulated by the balance between cyclin-dependent kinases (CDKs) and CDK inhibitors such as p27. In neonatal cardiomyocytes, p27 is a key inhibitor of cell proliferation (6) and cyclin D1 is important for cell cycle progression (36). To delineate the pathway through which TIMP-3 inhibits neonatal cardiomyocyte proliferation, the effect of TIMP-3 on cyclin D1 and p27 expression was investigated. Our data showed that cyclin D1 was increased in TIMP-3−/− cardiomyocytes and decreased in rTIMP-3-treated cells as compared with WT. Consistent with these results, p27 expression was decreased in the TIMP-3−/− cardiomyocytes and neonatal hearts as compared with WT. This decrease in p27 expression resulted in an increase in cardiomyocyte proliferation both in vitro and in vivo. Furthermore, treatment of cardiomyocytes with rTIMP-3 resulted in a significant increase in p27 expression, which led to a significant decrease in cardiomyocyte proliferation. Our data suggest that ...
Home » meis1 regulates cyclin D1 and c-myc expression, and controls the proliferation of the multipotent cells in the early developing zebrafish ...
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
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
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 ...
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 findings herein advance a strategy for inducing myocardial repair in pediatric patients. Myocardial regeneration experiments in neonatal mice were not feasible until the recent introduction of techniques for inducing myocardial injury (15, 17, 41). LAD ligation (16, 17) and amputation injury (15, 42) in neonatal mice were reported to lead to scarless repair, although these results are controversial (43, 44). Here, we verify that cryoinjury is a technically feasible method that produces scar formation and dysfunction, which is in line with the scar formation and delayed repair process observed in zebrafish (31-33) and neonatal mice (35, 36) after cryoinjury. We also show that cryoinjury in neonatal mice is a useful model for human infants with heart disease because it recapitulates the scar formation, dysfunction, and decrease in cardiomyocyte cell cycle activity frequently seen in young patients with heart disease. The observed decrease in cardiomyocyte proliferation after cryoinjury ...
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 ...
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 ...
Sigma-Aldrich offers abstracts and full-text articles by [Diana C Canseco, Wataru Kimura, Sonia Garg, Shibani Mukherjee, Souparno Bhattacharya, Salim Abdisalaam, Sandeep Das, Aroumougame Asaithamby, Pradeep P A Mammen, Hesham A Sadek].
1998 Jul 085Philips SemiconductorsProduct specificationHex D-type flip-flop with reset; positive-edge trigger74HC/HCT174DC CHARACTERISTICS FOR 74HCFor the DC characteristics see
Brooks AR, Shiffman D, Chan CS, Brooks EE, Milner PG (Apr 1996). "Functional analysis of the human cyclin D2 and cyclin D3 ... Cyclins function as regulators of cyclin-dependent kinases. Different cyclins exhibit distinct expression and degradation ... G1/S-specific cyclin-D2 is a protein that in humans is encoded by the CCND2 gene. The protein encoded by this gene belongs to ... "Entrez Gene: CCND2 cyclin D2". Mirzaa GM, Parry DA, Fry AE, Giamanco KA, Schwartzentruber J, Vanstone M, Logan CV, Roberts N, ...
CDK6; cyclin D1, cyclin D2, cyclin D3 CDK7; cyclin H CDK8; cyclin C CDK9; cyclin T1, cyclin T2a, cyclin T2b, cyclin K CDK10 ... cyclin A, cyclin B CDK2; cyclin A, cyclin E CDK3; cyclin C CDK4; cyclin D1, cyclin D2, cyclin D3 CDK5; CDK5R1, CDK5R2. See also ... Furthermore, cyclin binding determines the specificity of the cyclin-CDK complex for particular substrates. Cyclins can ... Viruses can encode proteins with sequence homology to cyclins. One much-studied example is K-cyclin (or v-cyclin) from Kaposi ...
Brooks AR, Shiffman D, Chan CS, Brooks EE, Milner PG (1996). "Functional analysis of the human cyclin D2 and cyclin D3 ... Cyclin-dependent kinase 4, Cyclin-dependent kinase 6, EIF3K, and Retinoic acid receptor alpha. Cyclin Cyclin D GRCh38: Ensembl ... Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which ... G1/S-specific cyclin-D3 is a protein that in humans is encoded by the CCND3 gene. The protein encoded by this gene belongs to ...
CDK6 is positively regulated primarily by its union to the D cyclins D1, D2 and D3. If this subunit of the complex is not ... A Cyclin-dependent kinase 6 interacts with: CDKN2C, Cyclin D1, Cyclin D3, P16, PPM1B, and PPP2CA. Cell cycle Cyclin-dependent ... It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein ... In mammalian cells, cell cycle is activated by CDK6 in the early G1 phase through interactions with cyclins D1, D2 and D3. ...
In mice and humans, two more cyclin D proteins have been identified. The three homologues, called cyclin D1, cyclin D2, and ... All six cyclin D-Cdk4,6 complexes (cyclin D1/D2/D3 with Cdk4/6) target Rb for phosphorylation through helix-based docking. The ... Other than Rb, viral cyclin D-Cdk6 complex also targets p27Kip, a Cdk inhibitor of cyclin E and A. In addition, viral cyclin D- ... The phosphorylation of Rb by cyclin A-Cdk2, cyclin B-Cdk1, and cyclin E-Cdk2 are unaffected. The C terminus has a stretch of 21 ...
This is consistent with the role of Pitx2 in regulating the growth-regulating genes cyclin D2, cyclin D1, and C-Myc. In renal ... promotes thyroid carcinogenesis by activation of cyclin D2". Cell Cycle. 9 (7): 1333-41. doi:10.4161/cc.9.7.11126. PMID ...
Tsunekawa, Yuji; Osumi, Noriko (November 2013). "Control of asymmetry distribution and the differentiation fate of Cyclin D2 in ...
... repress cyclin D1 and cyclin D2 promoter activity and encourages cell cycle arrest at cyclin G1 (CCNG1). As a result of that, ... Furthermore, FOXO1-mediated cell cycle arrest is linked with cyclin D1 and cyclin D2 suppression in mammals. It was detected ... The transcription and half- life of cyclin-dependent kinase inhibitor p27KIP1 rises when FOXO1 is active. A study detects that ... activation of FOXO1 prevents the cell-division cycle at cyclin G1 (CCNG1) out of one of two ways stimulating or suppressing ...
... "miR-497 and miR-302b regulate ethanol-induced neuronal cell death through BCL2 protein and cyclin D2". The Journal of ...
... A also raises cyclin D2 levels suggesting a role for the latter in macrophage activation besides proliferation. It ...
Other reported downstream ALK targets include FOXO3a, CDKN1B/p27kip, cyclin D2, NIPA, RAC1, CDC42, p130CAS, SHP1, and PIKFYVE. ...
Furthermore, Runx2 controls the gene expression of cyclin D2, D3, and the CDK inhibitor p21(cip1) in hematopoietic cells. It ... has been shown that on a molecular level, Runx associates with the cdc2 partner cyclin B1 during mitosis. The phosphorylation ...
Cyclin D2 and Twist in in situ and invasive lobular breast carcinoma". International Journal of Cancer. 107 (6): 970-5. doi: ...
Another mammalian CDK, Cdk2, can form complexes with cyclins D1, D2, D3, E, or A. Cdk4 and Cdk6 interact with cyclins D1, D2, ... During G2 phase, cyclin A is degraded, while cyclin B is synthesized and cyclin B-Cdk1 complexes form. Not only are cyclin B- ... cyclin-dependent kinase (CDK), with a regulatory subunit, cyclin. Once cyclin-dependent kinases bind to cyclin, the formed ... Cyclin Cyclin-dependent kinase Malumbres M, Barbacid M. Mammalian cyclin-dependent kinases. Trends Biochem. Sci. 2005 Nov;30(11 ...
... including some induction of cyclin D2 and Cdk4. Additionally, sustained ERK activity seems to be important for phosphorylation ... Cyclin D-bound cdks 4 and 6 are activated by cdk-activating kinase and drive the cell towards the restriction point. Cyclin D, ... Sustained mitogen signaling promotes cell cycle entry largely through regulation of the G1 cyclins (cyclin D1-3) and their ... including the major G1 cyclin, cyclin D1. Myc also regulates expression of a wide variety of pro-proliferative and pro-growth ...
Some of the downstream gene targets of human Gli1 include regulators of the cell cycle and apoptosis such as cyclin D2 and ...
"Deregulation of cyclin D2 by juxtaposition with T-cell receptor alpha/delta locus in t(12;14)(p13;q11)-positive childhood T- ...
... in part through direct downregulation of cyclin D2 and cyclin E2. miR-26a also directly suppresses expression of estrogen ... miR-26a again suppresses tumorigenesis in nasopharyngeal cells in vivo, with suppressed expression of c-myc, cyclins D3 and E2 ... 2011). "Tumor-specific expression of microRNA-26a suppresses human hepatocellular carcinoma growth via cyclin-dependent and - ... and cyclin-dependent kinases CDK4 and CDK6. p14ARF and p21CIPI CDK inhibitor expression are conversely enhanced, mediated ...
... perhaps because the overexpression of cyclin D2 is weaker than Bcl2 overexpression in driving cells to accumulate and become ... both located at 9p21.3 and respectively encoding cyclin dependent kinase inhibitor 2A and cyclin dependent kinase inhibitor 2B ... The overexpression of cyclin D1 is thought to be a major factor in the development of ISMCL and its progression to MCL. ... The cyclin D1-expressing lymphocytes generally populate the inner layers of the marginal zone but on occasion some of these ...
... a protein Levuglandin D2 Prostaglandin D2 receptor, a G-protein coupled receptor Resolvin D2 Cyclin D2 (CCND2) Vitamin D2, or ... Look up D2 in Wiktionary, the free dictionary. D2, D02, D.II, D II or D-2 may refer to: Dublin 2, a Dublin, Ireland postcode D2 ... Marcelo D2 (born 1967), Brazilian rapper D2, an abbreviation for DOCSIS 2.0, an international telecommunications standard D2 ... électronique d2, now trading as LaCie D2 kit, a microprocessor development kit MEK6800D2 D-2 (video), a professional digital ...
This has been attributed to high mRNA levels of G1-related Cyclin D2 and Cdk4 genes and low levels of cell cycle regulatory ... The cell cycle is regulated by complex network of cyclins, cyclin-dependent kinases (Cdk), cyclin-dependent kinase inhibitors ( ... hESCs show that the activities of Cyclin E/Cdk2 and Cyclin A/Cdk2 complexes are cell cycle-dependent and the Rb checkpoint in ... However, in mESCs, this typically ordered and oscillatory activity of Cyclin-Cdk complexes is absent. Rather, the Cyclin E/Cdk2 ...
Protomers consist of Isoreceptors D1-D2 D1-D3 D2-D3 D2-D4 D2-D5 Non-isoreceptors D1-adenosine A1 D2-adenosine A2A D2-ghrelin ... Sustained D1 receptor activity is kept in check by Cyclin-dependent kinase 5. Dopamine receptor activation of Ca2+/calmodulin- ... D2 is encoded by the Dopamine receptor D2 gene (DRD2), of which there are two forms: D2Sh (short) and D2Lh (long): The D2Sh ... The D2 class of receptors produce the opposite effect, as they are Gαi coupled receptors, and block the activity of adenylyl ...
... cyclin - cyclin A - cyclin B - cyclin E - cyclin-dependent kinase - cycloleucine - cyclosporin - cyclosporine - cystatin - ... dopamine D2 receptor - dopamine receptor - double helix - Drosophila - drugs - dynorphin eIF-2 - eIF-2 kinase - electrochemical ...
2004). "A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95". Biochem. J. 378 (Pt 2): 673-9. doi: ... D2/Eg7 for chromosome condensation in mitotic extract". J. Cell Biol. 149 (3): 531-6. doi:10.1083/jcb.149.3.531. PMC 2174845. ... AKAP8 has been demonstrated to interact with: Cyclin D3 DDX5, MCM2, MYCBP, and PRKAR2A. GRCh38: Ensembl release 89: ... "A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95". Biochem. J. 378 (Pt 2): 673-9. doi:10.1042/ ...
Rossitto M, Ujjan S, Poulat F, Boizet-Bonhoure B (2015). "Multiple roles of the prostaglandin D2 signaling pathway in ... Cyclin D1, Cdk4, and Insulin-like growth factor 1; and e) regulating agents such as HSP70, GPR78, Gadd153, Ubiquitin B, and ... "Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia". Science Translational ... a glutathione-independent synthase termed lipocalin-type Prostaglandin D2 synthase (PTGDS or L-PGDS) and a glutathione- ...
During prometaphase, dynactin also helps target polo-like kinase 1 (Plk1) to kinetochores through cyclin dependent kinase 1 ( ... but can be induced to form a tight complex in the presence of the N-terminal 400 amino acids of Bicaudal D2 (BICD2), a cargo ...
CDK2/cyclin E and CDK2/cyclin A complexes. Studies using TG mice model suggested the existence of an autocrine loop involving ... Recent studies described an inhibitor (D2) that block PELP1 interactions with AR. Since PELP1 interacts with histone ... Nair BC, Nair SS, Chakravarty D, Challa R, Manavathi B, Yew PR, Kumar R, Tekmal RR, Vadlamudi RK (September 2010). "Cyclin- ... the CDK-cyclin D1-PELP1 axis in promoting mammary tumorigenesis PELP1 has a histone binding domain; functions as a reader of ...
Phospholipase D2 (PLD-2) which is localized in the growth cone and is involved in actin cytoskeleton rearrangement, can be ... Studies suggest that glycogen synthase kinase-3β (GSK-3β) and cyclin-dependent protein kinase 5 (Cdk5) are highly expressed in ...
... cyclin a MeSH D23.348.353.120 - cyclin b MeSH D23.348.353.161 - cyclin d1 MeSH D23.348.353.180 - cyclin e MeSH D23.348.383.110 ... prostaglandin d2 MeSH D23.469.050.175.725.780 - prostaglandins e MeSH D23.469.050.175.725.780.050 - alprostadil MeSH D23.469. ...
... cyclin D1. The recruitment of TLS to the promoter of cyclin D1 is directed by long ncRNAs expressed at low levels and tethered ... "The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum". The Journal of ... Yik JH, Chen R, Nishimura R, Jennings JL, Link AJ, Zhou Q (October 2003). "Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA ... was recently shown that BC1 is associated with translational repression in dendrites to control the efficiency of dopamine D2 ...
Rulten SL, Hodder E, Ripley TL, Stephens DN, Mayne LV (July 2008). "Alcohol induces DNA damage and the Fanconi anemia D2 ... mice were found to die during embryogenesis and showed a drastic reduction in the production but increased expression of Cyclin ...
For instance, Cdk1 (Cyclin-dependent kinase 1) activates condensin I, whereas CK2 (Casein kinase 2) negatively regulate its ... Nevertheless, there are multiple paralogs for two of its regulatory subunits (CAP-D2 and CAP-H), and some of them specifically ... and a CAP-D2(ycs4)/CAP-H(brn1) subcomplex. A recent cryo-EM study has shown that condensin undergoes large conformational ...
... cyclin-dependent kinase EC 2.7.11.23: [RNA-polymerase]-subunit kinase EC 2.7.11.24: mitogen-activated protein kinase EC 2.7. ... dolichyl N-acetyl-α-D-glucosaminyl phosphate 3-β-D-2,3-diacetamido-2,3-dideoxy-β-D-glucuronosyltransferase EC 2.4.1.336: ...
p53 also upregulates the p21 protein, which blocks the formation of the cyclin D/Cdk4 complex, thereby preventing the ... D2 the Asian American type I variant, D3 the Asian American type II variant. The various lineages and sublineages have ...
Activation of cyclin D1 and D2 promoters by human T-cell leukemia virus type I tax protein is associated with IL-2-independent ... Our data suggest that induction of cyclins D1 and D2 by Tax is involved in IL-2-independent cell-cycle progression as well as ... A Tax mutant that did not activate NF-{kappa}B failed to activate cyclin D1 and D2 promoters. Inhibitors of NF-{kappa}B ( ... higher expression levels of cyclin D1 and D2 mRNA were detected in HTLV-I-infected T-cell lines, which were at least in part ...
Highly specific and rigorously validated in-house, Cyclin D2 (D52F9) Rabbit Monoclonal Antibody (CST #3741) is ready to ship. ... Monoclonal Antibody for studying Cyclin D2. Cited in 111 publications. Validated for Western Blotting, Immunoprecipitation. ... Cyclin D2 (D52F9) Rabbit mAb detects endogenous levels of total cyclin D2 protein. It does not cross-react with other family ... Cyclin D2 (D52F9) Rabbit mAb 3741. Toggle Between Dark and Light Modes Filter: *WB ...
IER3 and cyclin D2 gene expression in granulosa cells (18-20). BCL2A1 and IER3 are apoptosis inhibitors, whereas cyclin D2 is a ... BCL2A1 and cyclin D2 were investigated. IER3, BCL2A1 and cyclin D2 mRNA expression were detected using RT-qPCR, 48 h after ... Wang T, Li F and Tang S: MiR-30a upregulates BCL2A1, IER3 and cyclin D2 expression by targeting FOXL2. Oncol Lett 9: 967-971, ... miR-30a promotes BCL2A1, IER3 and cyclin D2 gene expression by suppressing FOXL2. The consequences of miR-30a knockdown and ...
... CCND2 protein solution (1mg/ml) containing 20mM Tris-HCl buffer (pH 8.0), 10% glycerol, 2mM DTT ... Cyclins serve as regulators of CDK kinases. Various cyclins demonstrate distinct expression and degradation patterns which ... CCND2 is a member of the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein ...
The CCND2 gene provides instructions for making a protein called cyclin D2. Learn about this gene and related health conditions ... Cyclins are a family of proteins that control how cells proceed through the multi-step cycle of cell division. Cyclin D2 helps ... Cyclin D2s role in the cell division cycle makes it a key controller of the rate of cell growth and division (proliferation) ... The cyclin D2 protein is regulated by a chemical signaling pathway called the PI3K-AKT-mTOR pathway. This signaling influences ...
Cyclin D2 is a GATA4 cofactor in cardiogenesis. Proceedings of the National Academy of Sciences 111(4), pp. 1415-1420. (10.1073 ... Cyclin D2 is a GATA4 cofactor in cardiogenesis. Proceedings of the National Academy of Sciences 111(4), pp. 1415-1420. (10.1073 ...
In addition, cyclin D2 level was down-regulated when OTUD-6B WT was overexpressed. Therefore, down-regulation of Otud-6b ... cyclin D1, cyclin D2, cyclin D3, p21, p27, p15, p16, cdk4, cdk6, cdc2, cyclin E, and Rb antibodies (CST). ... A & B & C. Real-time PCR, RT-PCR, and immunoblot of OTUD-6B, GAPDH, cyclin D1, cyclin D2, cyclin D3, p21, p27, p15, p16, cdk4, ... Knockdown of OTUD-6B has no effect on cyclin D2 level. A. The levels of Cyclin D2 had no difference when OTUD-6B was knocked ...
De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus ...
cyclin D2 (CCND2) 2.8 0.0450 8.7 W15574 EST −2.8 0.0056 2.1 AA062802 KIAA0354 KELCH-related 2.7 0.0001 0.1 ...
Mechanistically, cyclin D2, frequently thought to play a critical role in promoting tumor cell proliferation [34], was ... In CFPAC-1 and PANC-1 cells, GATA1 overexpression greatly improved Bcl-XL level and modestly enhanced cyclin D2, Mcl-1, MDR-1, ... Consistent with previous reports, Bcl-XL, cyclin D2, Bcl-2, Mcl-1, MDR-1, RRM1, and ABCG2 were upregulated, and dCK was ... In conclusion, cyclin D2 may play a substantial role in GATA1 mediated gemcitabine resistance. ...
CDKN2A; cyclin dependent kinase inhibitor 2A. 595 CCND1; cyclin D1. 894 CCND2; cyclin D2. ...
Notably, wild-type Nmyc1 retains its capacity to upregulate cyclin D1 and cyclin D2 4 days after infection despite the fact ... Cyclin D1, Neomarkers Ab-3; Cyclin D2, Santa-Cruz M-20; β-tubulin, Sigma T4026; phospho-GSK3β, CST 9331; phospho-S473 Akt, CST ... 2C), at 96 hours after infection, all three Nmyc1 proteins tested promoted increased levels of cyclin D1 and D2 relative to ... Hedgehog regulates cell growth and proliferation by inducing cyclin D and cyclin E. Nature ...
CCND2 gene encoded a protein termed G1/S-specific cyclin-D2, which belongs to the highly conserved cyclin family. CCND2 forms a ... Another down-regulated gene, CCND2 (cyclin D2) was picked out. CCND2 is one member of the cyclins that participate in promoting ... We also found that cyclin D2 (CCND2) was a novel target gene of miR-124, and was directly involved in miR-124-mediated ... Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis. Nature. 1996; 384:470-474. ...
They further identified cyclin D2 and cyclin-dependent kinase 6 as the downstream targets of this transcript. From this study, ...
These include Notch 1, cyclin D2, p21, MAP tau, and thymopoietin, most of which regulate cell cycle events. In addition, there ...
Association of cyclin D1 and D2 with the Myb DNA-binding domain could be demonstrated. Increased levels of cyclin D1 and D2 ... Here we demonstrate that the D-type cyclins, cyclin D1 and D2 in particular, specifically inhibit transcription when activated ... D-type cyclins repress transcriptional activation by the v-Myb but not the c-Myb DNA-binding domain EMBO JOURNAL Ganter, B., Fu ... Analysis of a cyclin D1 mutant and a dominant-negative CDK4 mutant implied that this repression is independent of complex ...
Colony-stimulating factor-1 receptor utilizes multiple signaling pathways to induce cyclin D2 expression.. Dey A et al. ...
MicroRNA-1-mediated inhibition of cardiac fibroblast proliferation through targeting cyclin D2 and CDK6. Front. Cardiovasc. Med ...
Activating inducers of proliferation, including Cyclin D2, E2F(1-3), Cks1, and Cul1; ... Early E2F-dependent transcription of cyclin E (which might also be a Myc target) leads to the formation of active cyclin-E-CDK2 ... p16INK4a binds to, and disrupts, cyclin-D-CDK complexes, which blocks G1-S progression both by preventing the cyclin-D-CDK4- ... Myc induces the expression of cyclin D and cyclin-dependent kinase (CDK)4, which together form an active kinase complex. Low- ...
Cyclins D1, D2 and D3 are Expressed in Distinct Tissues During Mouse Embryogenesis. Adriano Aguzzi, Markus Kiess, Daniela Ruedi ...
4) Ovaries of FSH-deficient mice demonstrate a modest decrease in cyclin D2 mRNA, without up-regulation of cell cycle inhibitor ... 4) Ovaries of FSH-deficient mice demonstrate a modest decrease in cyclin D2 mRNA, without up-regulation of cell cycle inhibitor ... 4) Ovaries of FSH-deficient mice demonstrate a modest decrease in cyclin D2 mRNA, without up-regulation of cell cycle inhibitor ... 4) Ovaries of FSH-deficient mice demonstrate a modest decrease in cyclin D2 mRNA, without up-regulation of cell cycle inhibitor ...
D2, and D3. In macrophages and fibroblasts, Cdk4-Cyclin D1 complexes are predominant. Much like Cdk2 and Cdc2, the activity of ... D2, and D3. In macrophages and fibroblasts, Cdk4-Cyclin D1 complexes are predominant. Much like Cdk2 and Cdc2, the activity of ... Active Cdk4-Cyclin D1 complexes are capable of phosphorylating the retinoblastoma gene product (pRb), but not histone H1 or ... Active Cdk4-Cyclin D1 complexes are capable of phosphorylating the retinoblastoma gene product (pRb), but not histone H1 or ...
be used for analyses of several tumor suppressor genes including APC1, Cyclin D2, RARB,. RASSF1A, Twist, Hin1 and GSTP1. From ...
There was no known role for cyclin D3 in human beta cell physiology," said Dr. Fiaschi-Taesch. Cyclin D2 is present in and ... Mice dont appear to make cdk6 naturally, but they do have cdk4 and cyclins D1 and D2, so standard rodent studies of beta ... particularly cyclin D3, stimulates human beta cell replication in test tubes. "We didnt expect cyclin D3 to ramp up beta cell ... and the team discovered that combining elevated amounts of the regulatory molecules cdk4 or cdk6 with a variety of D-cyclin ...
We noticed that one gene encoding cyclin D2 was upregulated in viruliferous guts. Cylin D2 (CCND2) is a member of the D-type ... Cyclin D2 plays a regulatory role in HBV replication. Virology. 2014;462:149-57. ... cyclin family, which associates the extracellular signaling environment with cell-cycle progression [30]. Moreover, cyclin D2 ... D-type cyclins are important downstream effectors of cytokine signaling that regulate the proliferation of normal and ...
LncRNA RNCR3 promotes endothelial cell proliferation and inflammatory cytokine secretion via regulating miR-185-5p/cyclin D2 ...
G1/S-specific cyclin-D2. Regulated Protein. CCND2_HUMAN [12] Heat shock protein beta-2. Regulated Protein. HSPB2_HUMAN ... G1/S-specific cyclin-D1 (CCND1). Clinical trial Target. Target Info [16] ... A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. J Cell Biol. 2008 Aug 11; ...
cyclin D2 [Source:HGNC Symbol;Acc.... 36677_at. 9276. COPB2. COPI coat complex subunit beta 2 .... ...
Cyclin D2 - Preferred Concept UI. M0528978. Scope note. 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.. ... Experiments using KNOCKOUT MICE suggest a role for cyclin D2 in granulosa cell proliferation and gonadal development. ... ciclina D2. Scope note:. Subtipo de ciclina D que está regulada por el FACTOR DE TRANSCRIPCIÓN GATA4. Los experimentos con ...
  • CCND2 is a member of the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. (neuromics.com)
  • The CCND2 gene provides instructions for making a protein called cyclin D2. (medlineplus.gov)
  • De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. (medlineplus.gov)
  • We also found that cyclin D2 (CCND2) was a novel target gene of miR-124, and was directly involved in miR-124-mediated suppressive effects on cell growth. (oncotarget.com)
  • The abundances of circ_0008360, miR-186-5p and cyclin D2 (CCND2) were examined via quantitative real-time polymerase chain reaction or western blot. (bvsalud.org)
  • Low-level phosphorylation of retinoblastoma (RB) family proteins by cyclin-D-CDK4 (or cyclin-D-CDK6, not shown) disrupts interactions between RB and E2F proteins, which relieves RB-mediated repression of E2F-target genes. (shu.edu)
  • p16INK4a binds to, and disrupts, cyclin-D-CDK complexes, which blocks G1-S progression both by preventing the cyclin-D-CDK4-mediated RB protein phosphorylation and by releasing sequestered p21CIP1 and p27KIP1. (shu.edu)
  • The Cdk4 kinase is a cell cycle-regulated cyclin-dependent kinase that associates with cyclins D1, D2, and D3. (bdbiosciences.com)
  • In macrophages and fibroblasts, Cdk4-Cyclin D1 complexes are predominant. (bdbiosciences.com)
  • The cdk-activating kinase (CAK) is a regulator of cdk-cyclin activity by virtue of its ability to phosphorylate single threonine residues on Cdk2, Cdc2, and Cdk4. (bdbiosciences.com)
  • Active Cdk4-Cyclin D1 complexes are capable of phosphorylating the retinoblastoma gene product (pRb), but not histone H1 or casein. (bdbiosciences.com)
  • Formation of the Cdk4-Cyclin D holoenzyme and phosphorylation of the catalytic subunit appear to be independently regulated. (bdbiosciences.com)
  • It is thought that p16 inhibition of Cdk4-Cyclin D interferes with cell cycle progression by preventing phosphorylation of pRb by Cdk4 and the subsequent release of factors that activate transcription. (bdbiosciences.com)
  • In a series of experiments, lead author Dr. Nathalie M. Fiaschi-Taesch, 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. (medindia.net)
  • We didn't expect cyclin D3 to ramp up beta cell replication so strongly when it was used with either cdk4 or cdk6. (medindia.net)
  • 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, noted Stewart. (medindia.net)
  • Cyclin D2's role in the cell division cycle makes it a key controller of the rate of cell growth and division (proliferation) in the body. (medlineplus.gov)
  • The resulting buildup of cyclin D2 in cells triggers them to continue dividing when they otherwise would not have, leading to abnormal cell proliferation. (medlineplus.gov)
  • It is less clear how a buildup of cyclin D2 contributes to polydactyly, although the extra digits are probably related to abnormal cell proliferation in the developing hands and feet. (medlineplus.gov)
  • Valkov N, King ME, Moeller J, Liu H, Li X, Zhang P . MicroRNA-1-mediated inhibition of cardiac fibroblast proliferation through targeting cyclin D2 and CDK6. (brown.edu)
  • Experiments using KNOCKOUT MICE suggest a role for cyclin D2 in granulosa cell proliferation and gonadal development. (bvsalud.org)
  • We identified a sub-network with a high number of shared, targeting miRNAs, of genes associated with cellular proliferation and cancer, including c-MYC and Cyclin D. (biomedcentral.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. (medindia.net)
  • There was no known role for cyclin D3 in human beta cell physiology," said Dr. Fiaschi-Taesch. (medindia.net)
  • Cyclins are a family of proteins that control how cells proceed through the multi-step cycle of cell division. (medlineplus.gov)
  • Our findings link HTLV-I infection to changes in cellular D-type cyclin gene expression, transformation of T cells and subsequent development of T-cell leukemia. (mdc-berlin.de)
  • Early E2F-dependent transcription of cyclin E (which might also be a Myc target) leads to the formation of active cyclin-E-CDK2 complexes. (shu.edu)
  • Cyclin-E-CDK2 functions in a positive-feedback loop to promote RB hyperphosphorylation. (shu.edu)
  • p21CIP1 and p27KIP1 inactivate cyclin-E-CDK2 complexes. (shu.edu)
  • p21CIP1 and p27KIP1 are also sequestered by active cyclin-D-CDK complexes, which frees cyclin-E-CDK2 from their inhibitory effects. (shu.edu)
  • Our aim was to examine the involvement of G1 cell-cycle regulators in cell growth dysregulation induced by HTLV-I. Compared to uninfected cells, higher expression levels of cyclin D1 and D2 mRNA were detected in HTLV-I-infected T-cell lines, which were at least in part mediated by the viral transforming protein Tax since Tax activated both cyclin D1 and D2 promoters in the human T-cell line Jurkat. (mdc-berlin.de)
  • 4) Ovaries of FSH-deficient mice demonstrate a modest decrease in cyclin D2 mRNA, without up-regulation of cell cycle inhibitor mRNAs associated with luteinization (i.e. p15, p27, and p21). (elsevier.com)
  • The cyclin D2 protein is regulated by a chemical signaling pathway called the PI3K-AKT-mTOR pathway. (medlineplus.gov)
  • Each of the known mutations changes a single protein building block (amino acid) in the cyclin D2 protein. (medlineplus.gov)
  • Tsunekawa Y, Kikkawa T, Osumi N. Asymmetric inheritance of Cyclin D2 maintains proliferative neural stem/progenitor cells: a critical event in brain development and evolution. (medlineplus.gov)
  • Thus, a peptidyl mimic of p21 WAF1/CIP1 that inhibits the interaction between cyclin-dependent kinase 4 and type D cyclins abrogated the in vitro proliferative response of T cells to histones and T-independent and T-dependent proliferative responses of B cells. (aai.org)
  • Quantitative multiplex methylation-specific PCR will be used for analyses of several tumor suppressor genes including APC1, Cyclin D2, RARB, RASSF1A, Twist, Hin1 and GSTP1. (knowcancer.com)
  • Los experimentos con empleo de RATONES NOQUEADOS (con genes desactivados) sugieren un papel de la ciclina D2 en la proliferación de las células de la granulosa y en el desarrollo gonadal. (bvsalud.org)
  • The activities of cyclin-CDK complexes are opposed by CDK inhibitors, which might be targets for Myc-mediated repression. (shu.edu)
  • Cyclin D2 helps to regulate a step in the cycle called the G1-S transition, in which the cell moves from the G1 phase, when cell growth occurs, to the S phase, when the cell's DNA is copied (replicated) in preparation for cell division. (medlineplus.gov)
  • Our data suggest that induction of cyclins D1 and D2 by Tax is involved in IL-2-independent cell-cycle progression as well as IL-2-independent transformation of primary human T cells by HTLV-I. High expression levels of cyclin D1 and D2 mRNAs were also detected in some patients with ATL. (mdc-berlin.de)
  • Western blot analysis of extracts from various cell lines using Cyclin D2 (D52F9) Rabbit mAb. (cellsignal.com)
  • Although components of the FSH null phenotype may be caused by partial cyclin D2 loss of function, these findings indicate that the mechanisms of granulosa cell cycle arrest in FSHβ knockout mice are distinct from those of cycle withdrawal at luteinization. (elsevier.com)
  • Various cyclins demonstrate distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (neuromics.com)
  • Myc induces the expression of cyclin D and cyclin-dependent kinase (CDK)4, which together form an active kinase complex. (shu.edu)
  • In occasional cells, this crossing over may lead to increased 12p copy number and overexpression of cyclin D2. (medscape.com)
  • Granulosal BRDU incorporation was also significantly reduced as were cyclin D2 and B1 immunoreactivities in Igf1 null compared with WT mice. (uandes.cl)
  • Overexpression of cyclin D3 is associated with poor clinical outcome in diffuse large B-cell lymphoma cases (5). (novusbio.com)
  • 7. Overexpression of cyclin D2 in chronic B-cell malignancies. (nih.gov)
  • In occasional cells, this crossing over may lead to increased 12p copy number and overexpression of cyclin D2. (medscape.com)
  • Importantly, we have shown that the positive staining reflected overexpression of cyclin Dl. (nii.ac.jp)
  • Overexpression of cyclin Dx mRNA in Hif2α morphants partially rescued zccndx expression. (elsevier.com)
  • Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. (wikidata.org)
  • We report a case of peripheral T-cell lymphoma not otherwise specified with heterogeneous nuclear Cyclin D1 immunohistochemical overexpression, due to gene copy gain, a phenomenon similar to that observed in Mantle Cell Lymphoma characterized by t(11;14)(q13;q32). (biomedcentral.com)
  • In this case report we underline the diagnostic pitfall rapresented by Cyclin D1 immunoistochemical overexpression in a T-cell lymphoma. (biomedcentral.com)
  • Here we report a case of Peripheral T-cell lymphomas Not Otherwise Specified with cyclin D1 gene copy gain associated with protein overexpression. (biomedcentral.com)
  • The cyclin D2 protein is regulated by a chemical signaling pathway called the PI3K-AKT-mTOR pathway. (medlineplus.gov)
  • [ 29 , 30 , 31 ] Previous analyses of cyclin D1 expression in low-grade B-cell lymphoproliferative disorders by flow cytometry have used an antibody that cross-reacts with cyclin D2. (medscape.com)
  • m-IgG Fc BP-HRP is the preferred secondary detection reagent for cyclin D2 Antibody (DCS-3) for WB and IHC(P) applications. (scbt.com)
  • This reagent is now offered in a bundle with cyclin D2 Antibody (DCS-3) ( see ordering information below ). (scbt.com)
  • Immunocytochemistry/ Immunofluorescence: Cyclin D3 Antibody [NBP1-31806] - HeLa cells were fixed in 4% paraformaldehyde at RT for 15 min. (novusbio.com)
  • Green: Cyclin D3 protein stained by Cyclin D3 antibody diluted at 1:200. (novusbio.com)
  • Immunohistochemistry-Paraffin: Cyclin D3 Antibody [NBP1-31806] - Rat lung. (novusbio.com)
  • Cyclin D3 antibody diluted at 1:500. (novusbio.com)
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Mouse Prostaglandin D2 Synthase, Hematopoietic (PTGDS) in serum, plasma, tissue homogenates and other biological fluids. (myelisakit.com)
  • These results suggest that cyclin D2 plays a key role in regulating the transition of β cells from quiescence to replication and may provide a target for the development of therapeutic strategies to induce expansion and/or regeneration of β cells. (jci.org)
  • These observations suggest that cyclin D1 may be involved as an important downstream target of varied upstream signals in mammary gland development and tumorigenesis (9). (q-vd-oph.com)
  • Considerable effort directed towards the identification of G1 cyclins has led to the isolation of cyclin D, cyclin C and cyclin E. Of these, cyclin D corresponds to a putative human oncogene, designated PRAD1, which maps at the site of the Bcl-1 rearrangement in certain lymphomas and leukemias. (scbt.com)
  • Climicopahologic Study of PRAD1/cyclin D1 overoxpressing lymphoma with special reference to mantle cell lymphoma,a sistinct molecular pathologic enntity. (nii.ac.jp)
  • The methylation status of Cyclin D2 was correlated with the methylation of nine other tumor suppressor genes published previously from our laboratory on the same set of samples (R. Maruyama et al. (nih.gov)
  • We also compared methylation of cyclin D2 with methylation of nine tumor suppressor genes [published previously from our laboratory (R. Maruyama et al. (nih.gov)
  • Los experimentos con empleo de RATONES NOQUEADOS (con genes desactivados) sugieren un papel de la ciclina D2 en la proliferación de las células de la granulosa y en el desarrollo gonadal. (bvsalud.org)
  • The expression of cyclin D2, D3, Cdk 2, 4 and 6 genes in WEHI-3B JCS cells was found to be down-regulated at 24 h as measured by RT-PCR. (monash.edu)
  • Other cell cycle genes up regulated incorporate CDK4 cyclin D2 and CDK7. (atpasepathway.com)
  • To map the positions of these genes more precisely, panels of congenic strains of mice (C.D2) have been constructed to contain regions of DBA/2 chromatin harboring the Pctr 1, 2 and 3 resistance genes on a BALB/c background. (nih.gov)
  • Catenin/TCF/LEF-1 complicated activates oncogenic focus on genes such as for example c-myc (6), c-jun (7) and cyclin D1 (8). (colinsbraincancer.com)
  • Negative regulation of G1 in mammalian cells: inhibition of cyclin E-dependent kinase by TGF-beta. (wikidata.org)
  • A p21(waf1)-self-employed pathway for inhibitory phosphorylation of cyclin-dependent kinase p34(cdc2) and concomitant G(2)/M arrest from the chemopreventive flavonoid apigenin. (welbourneprimary.com)
  • The D cyclins were expressed differentially in chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), and mantle cell lymphoma (MCL) with strong staining of cyclin D1 and D2 in MCL, strong staining of cyclin D1 but weak staining of cyclin D2 in 4 of 5 PLLs, and low-level staining for both cyclins in most CLLs. (medscape.com)
  • The CDK (p16/Rb/Cyclin D) and PI3K (mTOR, AKT) pathways implicated in mouse plasmacytomagenesis are frequently dysregulated in a number of human hematopoietic malignancies, including multiple myeloma, Burkitt's lymphoma and mantle cell lymphoma. (nih.gov)
  • Cdk4 in combination with either cyclin Dl or cyclin D2 is also able to form a ternary complex with retinoblastoma protein (pRb), and cyclin D2-Cdk4 was able to phosphorylate the pRb to which it was bound. (ucl.ac.uk)
  • Component of the ternary complex, cyclin D2/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex (By similarity). (nih.gov)
  • Death-effector domain-containing protein DEDD is an inhibitor of mitotic Cdk1/cyclin B1. (kumamoto-u.ac.jp)
  • Recombinant protein encompassing a sequence within the center region of human Cyclin D3. (novusbio.com)
  • Using bimolecular fluorescence complementation (BiFC) in living cells, we showed that aswell as the MOR, HINT1 and 1R can associate using the cannabinoid CB1, dopamine D1 and D2, serotonin 1A and 2A, and metabotropic glutamate 2 and 5 receptors. (baxkyardgardener.com)
  • We used a novel approach, cyclin D2 knockout mice (D2 KO mice), specifically lacking adult brain neurogenesis to verify its importance in learning and memory. (uzh.ch)
  • Cyclin D3 expression has been linked to inhibition of granulocyte differentiation and activation of various transcription factors, such as transcription factor 5 (3, 4). (novusbio.com)
  • Quantitative real-time PCR and also western soak up research says cyclin D1, E1, SKP2, as well as pRB had been down-regulated upon SMO inhibition together with cyclopamine. (healthweblognews.info)
  • D2 KO mice showed no impairment in sensorimotor tests, with only sensory impairment in an olfaction-dependent task. (uzh.ch)
  • Cyclin-dependent regulation of G1 in mammalian fibroblasts. (wikidata.org)
  • Cyclin-dependent kinase 2 is structured in two lobes. (wikipedia.org)
  • download collaboration in performance practice premises workings and failures 2016 of face by cyclin D- and cyclin E-dependent stairs has it complete as a end of the S JSTOR® and not has error page( Mittnacht, 1998). (online.de)
  • Kretanje elija kroz elijski ciklus je vo eno putem serin/treonin kinaza, to jest enzima iz porodice ciklin zavisnih kinaza (cdk-cyclin dependent kinase). (org.rs)
  • Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. (nih.gov)
  • kinase (cdk)1 can be a core element of the cell routine equipment, and forms complexes with cyclins A and B to market S, G2 and M stage progression1C3. (careersfromscience.org)
  • All 3 D cyclins are key cell cycle regulatory molecules involved in oncogenesis. (medscape.com)
  • Regulatory component of the cyclin D2-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. (nih.gov)
  • GLI2 mediated this mitogenic outcomes of Shh through transcriptional service of cyclin D1 and cyclin D2 throughout building strands of hair [51]. (healthweblognews.info)
  • D2 KO mice and their wild-type siblings were tested in several behavioral paradigms, including those in which the role of adult neurogenesis has been postulated. (uzh.ch)
  • D2 KO mice also demonstrated correct reversal learning. (uzh.ch)
  • Using cyclin D2-/- mice, we demonstrate that cyclin D2 is required for the replication of endocrine cells but is expendable for exocrine and ductal cell replication. (jci.org)
  • As a result, 14-day-old cyclin D2-/- mice display dramatically smaller islets and a 4-fold reduction in β cell mass in comparison to their WT littermates. (jci.org)
  • Consistent with these morphological findings, the cyclin D2-/- mice are glucose intolerant. (jci.org)
  • β cell mass in WT and cyclin D2 -/- mice during postnatal development. (jci.org)
  • The cyclin D2 -/- mice weights do not differ from their littermates. (jci.org)
  • 2002). In PIK3CA\mutant mice produced by us, we noticed how the PIK3CA\mutant glands possess a rise in triggered \catenin as well as the downstream cyclin D1. (researchreport-digital.com)
  • I have isolated two D-type cyclins and a putative kinase partner related to Cdk4 from the frog Xenopus laevis. (ucl.ac.uk)
  • 4. Relationship between cyclin D1 and p21(Waf1/Cip1) during differentiation of human myeloid leukemia cell lines. (nih.gov)
  • The RNA and protein levels of D-type cyclins and Cdk4 were followed during Xenopus early embryonic development. (ucl.ac.uk)
  • The two D-type cyclins and Cdk4 are absent during the early rapid cleavage phase of Xenopus development. (ucl.ac.uk)
  • Two additional human type D cyclins, as well as their mouse homologs, have been identified. (scbt.com)
  • On the other hand, the kinase activities of the cyclin/CDK holoenzyme are negatively controlled by CDKIs. (q-vd-oph.com)
  • 10. Cyclin D expression in chronic lymphocytic leukemia. (nih.gov)
  • Cyclin D2 promoter methylation was analyzed in 101 prostate cancer samples by methylation-specific PCR. (nih.gov)
  • Methylation-specific PCR for cyclin D2 on the 8 carcinoma cases showed methylated state at the promoter region, demonstrating feasible evaluation of the methylation status. (elsevier.com)
  • Histone deacetylases (HDACs) are key regulators of the cell cycle that function through regulating expression of tumor suppressors (p21 and p27), c-Myc and cyclin D1. (nih.gov)
  • Cyclin D3 is a member of Cyclin D family which mediates cell cycle progression through the G1 phase. (novusbio.com)
  • We also found that PCA induced S-phase arrest of the VSMC cell cycle and suppressed cyclin D2 expression. (elsevier.com)
  • On the other hand, RhoU silencing led to a decrease in cell migration with the build up of actin stress fibers, together with a decrease in cyclin D2 manifestation and in cell cycle progression. (bio-zentrum.com)
  • Our own discoveries report that cyclopamine offered cell cycle public arrest through down-regulation involving cyclins plus pRb. (healthweblognews.info)
  • Whole-mount in situ hybridization revealed that cyclin Dl, Cdk4 and pRb mRNAs are localised to distinct regions of the developing embryo, in contrast to other cyclins which tend to be distributed rather homogeneously, if they are present at all. (ucl.ac.uk)
  • We show that during neonatal development, cyclin D2 expression in the endocrine pancreas coincides with the replication of endocrine cells and a massive increase in islet mass. (jci.org)
  • In contrast, cyclin D2 -/- littermates did not show any significant increase in β cell mass in the same period. (jci.org)
  • Hydrophobic interactions cause the C-helix to associate with another helix in the activating cyclin. (wikipedia.org)