Cyclin D1: 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.Cyclin D2: 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.Cyclin D3: A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.Cyclin A: 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.Cyclin D: 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.Cyclin E: A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.Cyclin B: 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.Cyclin B1: A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.Cyclin A1: A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.Cyclins: 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.Cyclin A2: A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.Cyclin-Dependent Kinase 4: 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.Cyclin-Dependent Kinases: 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.Cyclin G1: 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.Cyclin G: A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.Cell Cycle: 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.Cyclin-Dependent Kinase 2: 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.G1 Phase: 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.Genes, bcl-1: 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.Cyclin C: 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.Retinoblastoma Protein: 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.CDC2-CDC28 Kinases: 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.Cyclin B2: 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.Cyclin T: 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.Oncogene Proteins: Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).Cyclin H: 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.Cell Cycle Proteins: 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.S Phase: 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.Cyclin G2: 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.CDC2 Protein Kinase: 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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Cyclin-Dependent Kinase Inhibitor p21: 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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Cell Line, Tumor: A cell line derived from cultured tumor cells.Cyclin-Dependent Kinase Inhibitor p27: 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.Proto-Oncogene Proteins: 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.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Tumor Suppressor Proteins: 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.Cyclin I: 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, Messenger: 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.Mitosis: 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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Tumor Cells, Cultured: 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.G0 Phase: A quiescent state of cells during G1 PHASE.Lymphoma, Mantle-Cell: 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).Signal Transduction: 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.Down-Regulation: 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.Cyclin-Dependent Kinase Inhibitor p16: 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.Blotting, Western: 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.Promoter Regions, Genetic: 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.Transfection: 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.Proliferating Cell Nuclear Antigen: 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.Cell Nucleus: 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)Apoptosis: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Gene Expression Regulation: 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.G2 Phase: 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.E2F Transcription Factors: 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.beta Catenin: 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: 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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.3T3 Cells: 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.Protein Binding: 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.Glycogen Synthase Kinase 3: 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.Ki-67 Antigen: 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 Transformation, Neoplastic: 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.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Breast Neoplasms: Tumors or cancer of the human BREAST.F-Box Proteins: 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, Cultured: 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.Tumor Suppressor Protein p53: 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.Reverse Transcriptase Polymerase Chain Reaction: 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.Molecular Sequence Data: 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.DNA-Binding Proteins: 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.RNA, Small Interfering: 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.Proto-Oncogene Proteins c-myc: 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.NIH 3T3 Cells: 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/)E2F1 Transcription Factor: 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.Mutation: 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.Nuclear Proteins: 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.Enzyme Activation: 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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Flow Cytometry: 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.Transcription Factor DP1: 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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Chromosomes, Human, Pair 11: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Up-Regulation: 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.Retinoblastoma-Like Protein p107: 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.cdc25 Phosphatases: A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.Neoplasm Proteins: 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.Retinoblastoma-Binding Protein 1: 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.Proteasome Endopeptidase Complex: 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.S-Phase Kinase-Associated Proteins: 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.HeLa Cells: 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.Cell Cycle Checkpoints: 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.Tumor Markers, Biological: 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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Recombinant Fusion Proteins: 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.Immunoblotting: 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.Proto-Oncogene Proteins c-akt: 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.Precipitin Tests: 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.DNA Primers: 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.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Amino Acid Sequence: 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.RNA Interference: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Epithelial Cells: 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.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Microtubule-Associated Proteins: 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.Chromosomes, Human, Pair 14: A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.Mammary Glands, Animal: MAMMARY GLANDS in the non-human MAMMALS.Models, Biological: 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.Protamine Kinase: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Cyclin-Dependent Kinase Inhibitor Proteins: 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.Threonine: 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.Carcinoma, Squamous Cell: 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)G1 Phase Cell Cycle Checkpoints: 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.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Phosphatidylinositol 3-Kinases: 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.Maturation-Promoting Factor: 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.Mitogen-Activated Protein Kinases: 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).Mice, Knockout: 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.Luciferases: 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.DNA: 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).Genes, myc: 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.Immunoprecipitation: 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.Mice, Nude: 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.Cell Growth Processes: Processes required for CELL ENLARGEMENT and CELL PROLIFERATION.Active Transport, Cell Nucleus: Gated transport mechanisms by which proteins or RNA are moved across the NUCLEAR MEMBRANE.Cyclin-Dependent Kinase 9: 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.Bromodeoxyuridine: 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.Ubiquitins: 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.Cytoplasm: 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)Starfish: Echinoderms having bodies of usually five radially disposed arms coalescing at the center.Gene Amplification: 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.DNA Replication: The process by which a DNA molecule is duplicated.E2F4 Transcription Factor: 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.Ubiquitin-Protein Ligase Complexes: 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).Blotting, Northern: 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.Prognosis: 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.STAT3 Transcription Factor: 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.
"Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclins". Cell. 67 ... Tiefenbrun N, Melamed D, Levy N, Resnitzky D, Hoffman I, Reed SI, Kimchi A (1996). "Alpha interferon suppresses the cyclin D3 ... In particular, it is stabilized in metaphase cells and is degraded upon metaphase exit akin to Cyclin B. It is competent to ... Huang TS, Shu CH, Yang WK, Whang-Peng J (Jul 1997). "Activation of CDC 25 phosphatase and CDC 2 kinase involved in GL331- ...
... differential signaling requirements for activation of assembled cyclin D3-cdk4 complexes in B-1 and B-2 lymphocyte subsets". ... 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 ... "The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2". The ...
A Cyclin-dependent kinase 6 interacts with: CDKN2C, Cyclin D1, Cyclin D3, P16, PPM1B, and PPP2CA. Cell cycle, Mitosis, CDK, ... Kaldis P, Ojala PM, Tong L, Mäkelä TP, Solomon MJ (Dec 2001). "CAK-independent activation of CDK6 by a viral cyclin". Molecular ... It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein ... CDK6 is positively regulated primarily by its union to the D cyclins D1,D2 and D3. If this subunit of the complex is not ...
Another mammalian CDK, Cdk2, can form complexes with cyclins D1, D2, D3, E, or A. Cdk4 and Cdk6 interact with cyclins D1, D2, ... The fluctuation controls the activation of the cyclin-CDK complexes and ultimately the progression throughout the cycle. See ... 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 ...
2006). "Identification of extracellular signal-regulated kinase 3 as a new interaction partner of cyclin D3". Biochem. Biophys ... 2007). "Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5". J. Biol. Chem ... 2002). "gp120-mediated induction of the MAPK cascade is dependent on the activation state of CD4(+) lymphocytes". Blood. 100 (7 ...
CDK6; cyclin D1, cyclin D2, cyclin D3 CDK7; cyclin H CDK8; cyclin C CDK9; cyclin T1, cyclin T2a, cyclin T2b, cyclin K CDK10 ... However, activation of CDK5 does not require activation loop phosphorylation. Proteins with no homology to the cyclin family ... 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 ...
Requirement for cyclin D3 in germinal center formation and function Cell Research 6:631-646 (2010) Faust, TW., Chang, EH., ... J. Nuclear Medicine 42:138 (2001). Grimaldi, CM., Michael, DJ., and Diamond, B. Expansion and activation of a population of ... B cell receptor revision diminishes the autoreactive B cell response after antigen activation in mice. J. Clin. Invest. 118: ... Estrogen alters thresholds for B cell apoptosis and activation. J. Clin. Invest. 109:1625-1633 (2002). Newman, J., Rice, JS., ...
1996). "Alpha interferon suppresses the cyclin D3 and cdc25A genes, leading to a reversible G0-like arrest". Mol. Cell. Biol. ... 1994). "Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide ...
... -CDK4 also enables the activation of cyclin E-CDK2 complex by sequestering Cip/Kip family CDK inhibitory proteins p21 ... Lin J, Jinno S, Okayama H (April 2001). "Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls ... Cyclins function as regulators of CDKs (Cyclin-dependent kinase). Different cyclins exhibit distinct expression and degradation ... cyclin D1 is translocated to the IgH promoter leading to cyclin D1 overexpression. Chromosomal translocation of the cyclin D1 ...
... cyclins D3 and E2, and cyclin-dependent kinases CDK4 and CDK6. p14ARF and p21CIPI CDK inhibitor expression are conversely ... GSK-3β mRNA is a direct target of miR-26a,miR-26a-mediated reduction of GSK-3β results in activation of β-catenin and induction ... in part through direct downregulation of cyclin D2 and cyclin E2. miR-26a also directly suppresses expression of estrogen ... This REST/NRSF complex controls activation of the genes in turn responsible for control of neural stem cell differentiation. ...
The three homologues, called cyclin D1, cyclin D2, and cyclin D3 are expressed in most proliferating cells and the relative ... "Activation of the cyclin D1 gene by the E1A-associated protein p300 through AP-1 inhibits cellular apoptosis". The Journal of ... Other than Rb, viral cyclin D-Cdk6 complex also targets p27Kip, a Cdk inhibitor of cyclin E and A. In addition, viral cyclin D- ... among which is cyclin D. In this way, cyclin D is synthesized as long as the growth factor is present. Even though cyclin D ...
Hedberg Y, Ljungberg B, Roos G, Landberg G (May 2003). "Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma ... This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the ... "HIV-1 tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation". The Journal of Biological Chemistry. 272 ( ...
Despouy G, Bastie JN, Deshaies S, Balitrand N, Mazharian A, Rochette-Egly C, Chomienne C, Delva L (February 2003). "Cyclin D3 ... Benkoussa M, Brand C, Delmotte MH, Formstecher P, Lefebvre P (July 2002). "Retinoic acid receptors inhibit AP1 activation by ... and gene activation". J. Biol. Chem. 279 (1): 319-25. doi:10.1074/jbc.M307621200. PMID 14581481. Farooqui M, Franco PJ, ... thyroid hormone and vitamin D3 signalling". Nature. 355 (6359): 446-9. doi:10.1038/355446a0. PMID 1310351. Kastner P, Perez A, ...
Sustained D1 receptor activity is kept in check by Cyclin-dependent kinase 5. Dopamine receptor activation of Ca2+/calmodulin- ... D3 is encoded by the Dopamine receptor D3 gene (DRD3). Maximum expression of dopamine D3 receptors is noted in the islands of ... There are at least five subtypes of dopamine receptors, D1, D2, D3, D4, and D5. The D1 and D5 receptors are members of the D1- ... Furthermore, D1-2 receptor subtypes are found at 10-100 times the levels of the D3-5 subtypes. The D1-like family receptors are ...
In addition, CDK8 promotes transcriptional activation mediated by the tumor suppressor protein p53, indicating that it may have ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... CDK8, K35, cyclin-dependent kinase 8, cyclin dependent kinase 8 ... Rickert P, Corden JL, Lees E (Jan 1999). "Cyclin C/CDK8 and cyclin H/CDK7/p36 are biochemically distinct CTD kinases". Oncogene ... The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate ...
Furthermore, Runx2 controls the gene expression of cyclin D2, D3, and the CDK inhibitor p21(cip1) in hematopoietic cells. It ... "Physical interaction of the activator protein-1 factors c-Fos and c-Jun with Cbfa1 for collagenase-3 promoter activation". The ... has been shown that on a molecular level, Runx associates with the cdc2 partner cyclin B1 during mitosis. The phosphorylation ...
... induction of cyclin D3 and p21 expression". Gut. 46 (4): 507-514. doi:10.1136/gut.46.4.507. ISSN 0017-5749. PMID 10716680. ... The loss of DNMT1 occurred from profound effects associated with activation of differentiation genes and loss of genes ...
Berg JP, Ree AH, Sandvik JA, Taskén K, Landmark BF, Torjesen PA, Haug E (Dec 1994). "1,25-dihydroxyvitamin D3 alters the effect ... "Phosphorylation of the regulatory subunit of type II beta cAMP-dependent protein kinase by cyclin B/p34cdc2 kinase impairs its ... "HIV inhibits the early steps of lymphocyte activation, including initiation of inositol phospholipid metabolism". Journal of ...
Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... FLIP inhibits the activation of caspase-8.[33] Binding of this ... Following TNF-R1 and Fas activation in mammalian cells a balance between proapoptotic (BAX,[37] BID, BAK, or BAD) and anti- ... The binding of TNF-alpha to TNFR1 has been shown to initiate the pathway that leads to caspase activation via the intermediate ... Oncoproteins E6 and E7 still leave p53 inactive, but they are not able to avoid the activation of caspases induced from the ...
Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... Walker SJ, Wu WJ, Cerione RA, Brown HA (May 2000). "Activation ... Böck BC, Vacratsis PO, Qamirani E, Gallo KA (May 2000). "Cdc42-induced activation of the mixed-lineage kinase SPRK in vivo. ... Kim AS, Kakalis LT, Abdul-Manan N, Liu GA, Rosen MK (March 2000). "Autoinhibition and activation mechanisms of the Wiskott- ... "Structural basis for the selective activation of Rho GTPases by Dbl exchange factors". Nature Structural Biology. 9 (6): 468-75 ...
... has been shown to interact with Estrogen receptor alpha, Cyclin-dependent kinase 8, Calcitriol receptor and BRCA1. GRCh38 ... "Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex". Nature. 398 (6730): 824-8. doi: ... "A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances VDR ... "Composite co-activator ARC mediates chromatin-directed transcriptional activation". Nature. 398 (6730): 828-32. doi:10.1038/ ...
Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... "VDAC2 inhibits BAK activation and mitochondrial apoptosis". ...
A cyclin forms a complex with Cdk, which begins to activate but the complete activation requires phosphorylation, as well. ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... cyclin D (Cdk4) cyclin E (Cdk2) cyclin E, A (Cdk2,1) cyclin A, ... cyclin E, A (Cdk2,1) cyclin A, B, B3 (Cdk1) H. sapiens cyclin D 1,2,3 (Cdk4, Cdk6) cyclin E (Cdk2) cyclin A (Cdk2, Cdk1) cyclin ... Cyclin A / CDK2 - active in S phase.. *Cyclin D / CDK4, Cyclin D / CDK6, and Cyclin E / CDK2 - regulates transition from G1 to ...
As a side note, the discovery that damages causes Cyclin D - Cdk 4/6 activation even in G0 cells should be kept in mind when ... 14 38.73 cM,14 D3. Start. 73,183,673 bp[2]. End. 73,325,822 bp[2]. ... One such example of E2F-regulated genes repressed by Rb are cyclin E and cyclin A. Both of these cyclins are able to bind to ... When E2F is free it activates factors like cyclins (e.g. cyclin E and cyclin A), which push the cell through the cell cycle by ...
... has been shown to interact with: AKT1, CKS1B, Cyclin D3, Cyclin E1, Cyclin-dependent kinase 2, Cyclin-dependent kinase 4 ... The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the ... Likewise, p27Kip1 is able to bind other Cdk proteins when complexed to cyclin subunits such as Cyclin E/Cdk2 and Cyclin A/Cdk2 ... Lin J, Jinno S, Okayama H (2001). "Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's ...
... domain that allow it to bind CDK in a region that blocks its ability to complex with cyclins and thus prevent CDK activation.[ ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase ... cyclin binding. • cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine ... p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin- ...
1999) Cytokinin activation of Arabidopsis cell division through a D-type cyclin. Science 283: 1541-1544. ... Furthermore, ppd and ninja mutants have a similar increase in the expression of CYCLIN D3;2 (CYCD3;2), and ectopic ... Arabidopsis Leaf Flatness Is Regulated by PPD2 and NINJA through Repression of CYCLIN D3 Genes. Alexandra Baekelandt, Laurens ... S4D). Arabidopsis has three D3-type cyclins, which were considered previously to act redundantly (Dewitte et al., 2007). In ...
B, After 24 h of activation, transfected T cells were tested for the expression of HuR and cyclin D3 by Western blot. The ... To determine the role of the cyclin D3 3′-UTR on the cyclin D3 mRNA instability induced by the L-Arg deprivation, the cyclin D3 ... A, Similar expression of cyclin D3 in selected clones of EBV cells transfected with cyclin D3 ORF or cyclin D3 cDNA plasmids. B ... Transfection of cells with cyclin D3 open reading frame or cyclin D3 cDNA. Cyclin D3-negative cell line EBV-Em, generated ...
CDK11p58 Promotes Microglia Activation via Inducing Cyclin D3 Nuclear Localization. Biyu Shen, Tianyu Gu, Haoyang Chen, Qian ... AGEs Decreased SIRT3 Expression and SIRT3 Activation Protected AGEs-Induced EPCs Dysfunction and Strengthened Anti-oxidant ...
Cyclin D3 is an essential d-type cyclin for normal expansion of T-cell progenitors (18). Cyclin D2 and D3 have nonredundant ... 2007) Faithful activation of an extra-bright red fluorescent protein in "knock-in" Cre-reporter mice ideally suited for lineage ... D) Cyclin D3 and CDK6 protein in Raptor-deficient developing T cells in vitro. (E) mRNA expression of Cyclin D3 (Ccnd3) and ... Cyclin D3 and CDK6 protein in Rictor-deficient developing T cells in vitro. (G) Protein amount of Cyclin D2, D3, and CDK6 in ...
... it facilitates activation of cyclin D-CKD4/6 complexes and inhibits activity of cyclin-CDK2 complexes (57) . The redistribution ... GFP vector and cyclin D3 (Cyclin D3), or PTEN and cyclin D3 (PTEN + Cyclin D3). Twenty-four h after transduction, the DNA ... If decreased cyclin D3 expression is required for PTEN-induced cell cycle arrest, then enforced expression of cyclin D3 should ... cyclin D3 levels remained unchanged (Fig. 7) ⇓ . Therefore, decreased levels of cyclin D3 were directly associated with cell ...
... activation-induced cytidine deaminase); Mm00441964-g1 (Trp53); Mm0043259-m1 (cyclin D1); Mm01612362-m1 (cyclin D3); and ... Cdk2, Cdk4, Cdk6, cyclin D1, cyclin D2, cyclin D3, and cyclin E2 were investigated. Two representative samples of five are ... Cdks and cyclins in c-myc-3′RR/p53+/− lymphomas. D-type cyclins (D1, D2, and D3) are G1-specific cyclins that associate with ... In agreement with their high Ki67 index, high amounts of free cyclin D1, D2, and D3 as well as Cdk-cyclin D1 and Cdk-cyclin D2 ...
... and mutational activation of Cdk4 can cause pancreatic hyperplasia (Rane et al., 1999). Likewise, overexpressed cyclin D3 can ... Zimmet JM, Ladd D, Jackson CW, Stenberg PE and Ravid K (1997) A role for cyclin D3 in the endomitotic cell cycle. Mol Cell Biol ... Rodriguez‐Puebla ML, LaCava M and Conti CJ (1999) Cyclin D1 overexpression in mouse epidermis increases cyclin‐dependent kinase ... These genes, the D‐type cyclin CycD1, its target pRb and the specific Cyclin D (CycD) inhibitor p16INK4A, were discovered as ...
The treatment of quiescent cells with growth factors results in the transcriptional activation of the D-type cyclin genes ... The human cyclin D3 gene has a TATA-less promoter and a single dominant initiation site. The minimal cyclin D3 promoter ... I have been defining the cis-acting elements and trans-acting factors that control transcription of the human cyclin D3 gene in ... Genomic clones for the human cyclin D3 gene, isolated from a human chromosome 6 library, were analysed by restriction ...
Furthermore, trans-activation of cyclin D3 by ER-E2F1 occurs even in the presence of the protein synthesis inhibitor ... In the present work, we present novel evidence that a second G(1) cyclin, cyclin D3, is also potently activated by E2F1. First ... Second, all of the growth-stimulatory members of the E2F family (E2F1, -2, and -3A) potently activate a cyclin D3 promoter ... Finally, mapping experiments localize the essential E2F regulatory element of the cyclin D3 promoter to a noncanonical E2F site ...
2C and D). IHC for cyclin D3, a known IL11-regulated cell-cycle target, showed a reduction in cyclin D3 protein levels in HEC1A ... Stat3 activation in human endometrial and cervical cancers. Br J Cancer 2007;96:591-9. ... Involvement of cyclin D3, CDKN1A (p21), and BIRC5 (Survivin) in interleukin 11 stimulation of decidualization in mice. Biol ... However, there was no effect of IL11Rα inhibition on cyclin D3 levels in Ishikawa tumors. This finding coincided with a more ...
2008). Ectopic expression of cyclin D3 corrects differentiation of DM1 myoblasts through activation of RNA CUG-binding protein ... the interaction of CUGBP1 with eIF2α and Cyclin D3-CDK4/6 seems to be crucial to achieve a correct myogenic differentiation. ... In this regard, activation of p38 signaling in dividing aged satellite cells induces the differentiation of both daughter cells ... In skeletal muscle, autophagy seems to participate in the activation of quiescent satellite cells, probably providing the ...
... possibly through activation of target genes (cyclin D1(D2,D3)/Cdk4(6) and cyclin E/Cdk2). In that regard, although MYC activity ... S1 B). Although qPCR after day 15 suggested that, in four-factor iPSCs, activation of OCT3/4 Tg and/or c-MYC Tg might affect ... Integrin activation and the structure of human iPSC platelets are comparable to those in human PB-derived platelets. (A-C) ... 7, A and B). In contrast, platelets produced from SeV-iPSCs-MKs in the absence of c-MYC O/E after its activation responded well ...
... differential signaling requirements for activation of assembled cyclin D3-cdk4 complexes in B-1 and B-2 lymphocyte subsets". ... 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 ... "The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2". The ...
Selected quality suppliers for anti-Cyclin D3 antibodies. ... Order monoclonal and polyclonal Cyclin D3 antibodies for many ... FGF2 signaling results in the phosphorylation of Erk1/2, and activation of c-Fos and c-Jun that lead to elevated cyclin D mRNA ... Protein level used designations for anti-Cyclin D3 (CCND3) Antibodies cyclin D3 , G1/S-specific cyclin-D3 , D3-type cyclin , G1 ... Top referenced anti-Cyclin D3 Antibodies. Show all anti-Cyclin D3 (CCND3) Antibodies with Pubmed References. * Human Monoclonal ...
Surprisingly, DEPTOR is highly overexpressed in a subset of multiple myelomas harboring cyclin D1/D3 or c-MAF/MAFB ... In these cells, high DEPTOR expression is necessary to maintain PI3K and Akt activation and a reduction in DEPTOR levels leads ...
LPTs failed to upregulate cyclin-dependent kinase 4 and cyclin D3, but Rb phosphorylation and cyclin A and B1 upregulation were ... In contrast, CD2 activation induced modest PBT but vigorous LPT cycling. The doubling time of CD3-activated PBTs was 1 day, ... This abnormality was partially reversed by in vitro addition of IL-2, which was also able to induce NF-κB activation. In one ... The Th1 cytokines IL-2 and IFN-γ, which inhibit T cell proliferation and promote activation induced cell death, may be required ...
... publishes original research and review articles on advances in basic research focusing on mechanisms involved in the activation ... D. A. Sarruf, I. Iankova, A. Abella, S. Assou, S. Miard, and L. Fajas, "Cyclin D3 promotes adipogenesis through activation of ... Thus, several players in cell cycle control, such as cyclin D3 and CDK4, have been reported to promote adipogenesis through ... cyclin D3, and E2F4 [73-75]. However, the capacity of these interactions to influence PPARγ-dependent pathways in adipocytes or ...
... aberrant WNT activation and probable CDK4 and CDK6 activation mediated through both increased cyclin D1 and cyclin D3 ... NanoString analysis also showed elevated expression of cyclin D3 (CCND3) and KRAS (Table 1), the latter being consistent with ... MAPK pathway activation is a hallmark of many cancers. Many genes in this pathway, including RAS, RAF (encoding the serine/ ... H and I) IHC for β-catenin (H) and cyclin D1 (I) shows strong nuclear and moderate cytoplasmic staining in both peripheral and ...
For cyclin D3 expression, MK derived from PMF CD34+ culture (D10) were labeled with a cyclin D3-FITC mAb (MOPC-21; BD ... Activation of FL/Flt3 axis in PMF MK cell cultures, in response to FL, induced activation of the p38-MAPK cascade, which is ... cyclin D3 expression and cytologic maturation (400×; C). D, effect of inhibitors and siRNA on CD41 expression and proplatelet ... and induced a nuclear localization of cyclin D3, known to promote endomitosis. It also stimulated MK differentiation as shown ...
The inhibition of cyclin D3 blocks the formation of these complexes. Thus, these studies provide a new function of cyclin D3, ... FSH and TSH activation of PKB and Sgk may occur via this alternative cAMP pathway that involves cAMP-GEFs and the activation of ... Cyclin D3 maintains growth-inhibitory activity of C/EBPalpha by stabilizing C/EBPalpha-cdk2 and C/EBPalpha-Brm complexes. Mol ... These results suggest that GEF-H1 may have a direct role in activation of Rac and/or Rho and in bringing the activated GTPase ...
The increase in β-cell proliferation was associated with upregulation of cyclins D1, D2, D3, and A and downregulation of p21. ... Phosphorylation/inactivation of GSK-3β and phosphorylation/activation of mTOR, critical regulators of D-cyclin expression and β ... Activation of Protein Kinase C-ζ in Pancreatic β-Cells In Vivo Improves Glucose Tolerance and Induces β-Cell Expansion via mTOR ... Activation of Protein Kinase C-ζ in Pancreatic β-Cells In Vivo Improves Glucose Tolerance and Induces β-Cell Expansion via mTOR ...
... leading to activation of caspases 7 and 3. These results demonstrate that the combination of AMPA and MAA can promote the ... The downregulated cyclin D3 may contribute to the cell cycle inhibition [32]. The combination of AMPA and MAA increased p21 and ... Burke, S.P.; Smith, L.; Smith, J.B. cIAP1 cooperatively inhibits procaspase-3 activation by the caspase-9 apoptosome. J. Biol. ... Induction of cell cycle arrest may be due to up-regulation of p21 expression at the early time and downregulation of cyclin D3 ...
Another mammalian CDK, Cdk2, can form complexes with cyclins D1, D2, D3, E, or A. Cdk4 and Cdk6 interact with cyclins D1, D2, ... The fluctuation controls the activation of the cyclin-CDK complexes and ultimately the progression throughout the cycle. See ... 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 ...
Cell division protein kinase 4; CMM3; Cyclin-dependent kinase 4; PSK-J3 The mammalian cell cycle is typically divided into four ... The structure of CDK4/cyclin D3 has implications for models of CDK activation. Proc Natl Acad Sci USA. 2009;106:4171-6.PubMed ... Loss of cyclin-dependent kinase 4 expression causes infertility and insulin-dependent diabetes while its activation results in ... The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. EMBO J ...
stage cyclins D1, D2, D3 and PCNA; whereas within 3 hours of 10% FBS serum-activation a majority (e.g. approximately 70%) ... Activation can be induced by, for example, electric shock (e.g., in electrofusion), the use of ionophores, ethanol activation, ... 0223] Activation of a Recombinant Embryo [0224] Activation refers to the beginning of embryonic development, e.g., replication ... stage cyclins D 1, 2,,3 and PNCA, and were therefore in G. 0 arrest. Restoration of the serum content to 10% for this line ...
  • Molecular Pathways: targeting the cyclin D-CDK4/6 axis for cancer treatment. (springer.com)
  • Identify tissue biomarkers (primarily the level of phosphorylation of individual C-terminal EGFR tyrosine sites, measured by nano-LC-MS/MS and markers of main downstream pathways activation such as P-AKT and P-ERK, measured by nano-LC-MS/MS and by more clinically standardized IHC) that best associate with response to neoadjuvant erlotinib hydrochloride treatment in patients with resectable squamous cell carcinoma of the head and neck (HNSCC). (clinicaltrials.gov)
  • Determine the best correlations between levels and changes of different individual biomarkers (e.g., levels of C-terminal EGFR phosphorylation and recruited adaptors and markers of downstream pathways activation) in order to evaluate the mechanisms of EGFR pathway activation in HNSCC and mechanisms of EGFR pathway inhibition by erlotinib hydrochloride in HNSCC tissue. (clinicaltrials.gov)
  • Because PLC activation results in the production of diacylglycerol (DAG), it is plausible that DAG-sensitive members, such as conventional isoforms α, βΙ, βΙΙ, and γ of the PKC family, may be involved in insulin-stimulated nuclear signaling pathways. (mcponline.org)
  • One such family of signaling pathways contains the cell cyclins. (cogprints.org)
  • In contrast to the transient activation of ERK by cytokines and growth factors, PAR-1 stimulation induces a sustained ERK activation through its coupling to multiple G-protein-linked signaling pathways, including Rho kinase. (jneurosci.org)
  • Previously, we have shown that FAK (focal adhesion kinase) and IGF-1R (insulin-like growth factor receptor-1) directly interact with each other and this interaction provides activation of crucial signaling pathways that benefit cancer cells. (ufl.edu)
  • For example, rodent β-cells can be induced to replicate using many strategies, including partial pancreatectomy, induction of obesity and insulin resistance, infusion of glucose, administration of growth factors, and activation of signaling pathways downstream of these growth factors and nutrients ( 1 - 8 ). (diabetesjournals.org)
  • Moreover we have also identified new pathways induced in ob/ob islets that remained unchanged in POKO islets, suggesting an important role for PPARγ in maintenance/activation of mechanisms essential for the continued function of the beta cell. (biomedcentral.com)
  • NMB or NMBR silencing inhibited M-CSF (zeige CSF1R Proteine )/ c-Fms (zeige CSF1R Proteine )-mediated downstream signaling pathways like activation of ERK (zeige EPHB2 Proteine ) and Akt (zeige AKT1 Proteine ) and induction of D-type cyclins, cyclin D1 and D2. (antikoerper-online.de)
  • In human lymphocytes, panobinostat alters key lymphocyte activation signaling pathways and is cytotoxic at concentrations much lower than that required for melanoma antitumor activity, resulting in an adverse therapeutic window. (aacrjournals.org)
  • In addition, increase in auxin and ABA levels/signals and the down-regulation of 40 over-represented AraCyc pathways indicated that stress-derived cellular responses may be involved in the activation of stress-induced re-orientation required for initiation of shoot growth. (biomedcentral.com)
  • Here, we report that murine bone marrow HPCs activation by the vascular Notch Delta4 ligand maintains a significant proportion of cells specifically in the G0 state. (inserm.fr)
  • Results show that cyclin D3 mRNA instability induced by L-Arg deprivation is dependent on response elements found in its 3′-untranslated region (UTR). (jimmunol.org)
  • The studies described in this report stemmed from the observation that the infected cell protein No.0 (ICP0) of herpes simplex virus 1 (HSV-1) binds to and stabilizes cyclin D3 ( 18 ). (asm.org)
  • Cyclin D1 translocations found in mantle cell lymphoma (MCL) take place during V(D)J recombination ( 1 ). (jimmunol.org)
  • The cyclin D1 or c- myc translocations often observed in plasma cell lymphoma (PCL) rather correspond to illegitimate CSR events ( 3 ). (jimmunol.org)
  • This cell cycle arrest correlated with an inability to increase cyclin D3 expression resulting from a decreased mRNA stability and an impaired translation. (jimmunol.org)
  • Enforced expression of cyclin D3 abrogated the PTEN-induced cell cycle arrest. (aacrjournals.org)
  • Cyclin D3 promotes pancreatic β-cell fitness and viability in a cell cycle-independent manner and is targeted in autoimmune diabetes. (semanticscholar.org)
  • Cyclin D3 is expressed in the majority of splenic diffuse red pulp small B-cell lymphomas. (antibodies-online.com)
  • However, the effect of direct PKC-ζ activation in the β-cell in vivo is unknown. (diabetesjournals.org)
  • In this study, we examined the effects of PKC-ζ activation in β-cell expansion and function in vivo in mice and the mechanisms associated with these effects. (diabetesjournals.org)
  • RESEARCH DESIGN AND METHODS We characterized glucose homeostasis and β-cell phenotype of transgenic (TG) mice with constitutive activation of PKC-ζ in the β-cell. (diabetesjournals.org)
  • CONCLUSIONS PKC-ζ, through mTOR activation, modifies the expression pattern of β-cell cycle molecules leading to increased β-cell replication and mass with a concomitant enhancement in β-cell function. (diabetesjournals.org)
  • Depending on the cyclin, various portions of the cell cycle are affected. (wikipedia.org)
  • Pre-B-cell expansion is driven by signals from the interleukin-7 receptor and the pre-B-cell receptor and is dependent on cyclin D3 and c-Myc. (asm.org)
  • Furthermore, the relationships between the repression of cyclin D3 and c-Myc and the induction of cell cycle inhibitor p27 are not known. (asm.org)
  • The essential roles of various levels of c-Myc, p27 quasi-complete inhibition/blocking, TP53 and/or p53 inactivation, as well as the perpetual hTERT activation of Telomerase biosynthesis are pointed out as key conditions for Malignant Cell transformations and partial re-differentiation leading to various types of cancer such as lung, breast,skin, prostate and colon. (cogprints.org)
  • The implications of the cyclin model for abnormal neural development during early development are being considered in this model that may lead to explanations of subsequent cognitive changes associated with abnormal neural cell differentiation in environmentally-affected embryos. (cogprints.org)
  • These data indicate that the cyclin D3-Cdk4 activity is necessary for cell cycle progression through G2 phase into mitosis and that the increased binding of p16 blocks this activity and G2 phase progression after UV exposure. (garvan.org.au)
  • Although protein levels of cdc2 remain relatively stable throughout the cell cycle, its activity is regulated by both the presence of cyclin partners (cyclins A and B) and its phosphorylation status. (pnas.org)
  • Many studies suggest a significant role for chronic CD4 + T-cell activation. (pubmedcentralcanada.ca)
  • IDO has been shown to be produced by MSCs stimulated by the proinflammatory cytokines released during T-cell activation. (bloodjournal.org)
  • We explored the presence, subcellular localization, and function of five early G1/S phase molecules-cyclins D1-3 and cdk 4 and 6-in the adult human β-cell. (diabetesjournals.org)
  • Our data suggest that the expansion of beta cell mass observed in ob/ob islets is associated with the activation of an immune response that fails to occur in POKO islets. (biomedcentral.com)
  • Cyclin D1 is unsuitable for minimal residual disease monitoring in bone marrow of patients with mantle cell lymphoma. (antikoerper-online.de)
  • in its absence, cyclins D2 and D3 are also not expressed, preventing hematopoietic cell division and differentiation at its earliest stage. (antikoerper-online.de)
  • The binding of growth factors, differentiation stimuli, and cytokines to cell surface receptors promotes the activation of the small GTPase Ras and dual phosphorylation (activation) of ERKs. (rupress.org)
  • This research is based on the hypothesis that the activation of particular stress signals in MDSC drives their ability to inhibit T cell responses and modulates MDSC accumulation and survival in tumors. (moffitt.org)
  • T cell-extrinsic CD18 attenuates antigen-dependent CD4+ T cell activation in vivo. (yale.edu)
  • Wu X, Lahiri A, Sarin R, Abraham C. T cell-extrinsic CD18 attenuates antigen-dependent CD4+ T cell activation in vivo. (yale.edu)
  • Unlike other cyclins that are periodically synthesized during cell cycle progression, expression and accumulation of D-cyclins are strongly dependent on extracellular mitogenic cues. (pubmedcentralcanada.ca)
  • Due to this property of D-cyclins, they are regarded as mitogenic sensors that relay signals from the extracellular environment to the core cell cycle machinery ( Sherr and Roberts, 1999 ). (pubmedcentralcanada.ca)
  • The results revealed that cholera toxin significantly induced G1 arrest and downregulated the expression of cyclin D1 and cyclindependent kinase 4/6 in the TCC cell lines, and this was rescued by KT5720. (spandidos-publications.com)
  • Unlike additional cyclins (cyclins A, E, and B) whose amounts oscillate through the cell routine, cyclin D amounts are more continuous but rely on the current presence of mitogens. (biomasswars.com)
  • Pancreatic Acinar Cell ERK activation. (pancreapedia.org)
  • The BTG2-PRMT2 module limits pre-B cell expansion by regulating the CDK4-Cyclin-D3 complex. (uni-freiburg.de)
  • B cell activation involves nanoscale receptor reorganizations and inside-out signaling by Syk. (uni-freiburg.de)
  • It might inhibit autoregulatory negative feedback loops in the MAPK pathway, with consequent resistance to cell death by ERK1 and ERK2 activation. (springeropen.com)
  • The arrest in cyclin D3 protein synthesis by L-Arg deprivation was triggered by the general control nonderepressible 2 (GCN2) kinase ( 8 ) and the subsequent phosphorylation of eukaryotic translation initiation factor 2 (eIF2)α ( 9 ). (jimmunol.org)
  • Moreover, hindering ERK1/2-dependent phosphorylation of c-Fos attenuates its release from the ERNF induced by serum and promotes its interaction with lamin A. Accordingly, serum stimulation rapidly releases preexisting c-Fos from the NE via ERK1/2-dependent phosphorylation, leading to a fast activation of AP-1 before de novo c-Fos synthesis. (rupress.org)
  • Christakos S, Raval-Pandya M, Wernyj RP, Yang W: Genomic mechanisms involved in the pleiotropic actions of 1,25-dihydroxyvitamin D3. (springer.com)
  • A significant correlation between activated ERK1/2 and cyclin D1 ( P = 0.031) in nodular, as well as between activated ERK1/2 and cyclin D3 ( P = 0.030) in SSMs were observed. (aacrjournals.org)
  • Activation of ERK1/2 did not have any impact on relapse-free or overall survival. (aacrjournals.org)
  • Moreover, the inverse association between membrane-bound β-catenin and ERK1/2 in NMs suggest that ERK1/2 activation may play a role in decreasing homotypic interactions through destabilization of β-catenin. (aacrjournals.org)