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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The treatment of quiescent cells with growth factors results in the transcriptional activation of the D-type cyclin genes during G1. Expression of the members of this family of cyclins, D1, 2 and 3, is spatially and temporally regulated with respect to growth factor receptor ligation. Transcription of these particular cyclins is proposed to monitor the growth factor signal and the encoded proteins participate in G1 progression. I have been defining the cis-acting elements and trans-acting factors that control transcription of the human cyclin D3 gene in T-cells. Genomic clones for the human cyclin D3 gene, isolated from a human chromosome 6 library, were analysed by restriction endonuclease digestion and a sub-clone extending 1.7kb upstream of exon 1 was sequenced and studied. The human cyclin D3 gene has a TATA-less promoter and a single dominant initiation site. The minimal cyclin D3 promoter sequence was identified as a region 173bp upstream of the transcription initiation site. Transient ...
THE D-type cyclins (D1, D2 and D3) are critical governors of the cell-cycle clock apparatus during the G1 phase of the mammalian cell cycle. These three D-type cyclins are expressed in overlapping, apparently redundant fashion in the proliferating tissues. To investigate why mammalian cells need three distinct D-type cyclins, we have generated mice bearing a disrupted cyclin D2 gene by using gene targeting in embryonic stem cells. Cyclin D2-deficient females are sterile owing to the inability of ovarian granulosa cells to proliferate normally in response to follicle-stimulating hormone (FSH), whereas mutant males display hypoplastic testes. In ovarian granulosa cells, cyclin D2 is specifically induced by FSH via a cyclic-AMP-dependent pathway, indicating that expression of the various D-type cyclins is under control of distinct intracellular signalling pathways. The hypoplasia seen in cyclin D2(-/-) ovaries and testes prompted us to examine human cancers deriving from corresponding tissues.
D-type cyclins (cyclin D1, D2 and D3) are components of the core cell cycle machinery. Rearrangements of cyclin D genes and overexpression of cyclin D proteins...
Plasmid -962 human cyclin D1 promoter EtsB site mutant pGL3Basic from Dr. Frank McCormicks lab contains the insert CCND1 and is published in Nature. 1999 Apr 1;398(6726):422-6. This plasmid is available through Addgene.
The generation of robust T-cell-dependent humoral immune responses requires the formation and expansion of germinal center structures within the follicular regions of the secondary lymphoid tissues. was only observed in mature GCs (Fig. ?(Fig.5D).5D). These data correlate with the lack of cyclin D2 manifestation in adult GCs and the requirement for cyclin D3 specifically at this stage. Based on our observation that cyclin D3 transcripts were observed in both follicular and GC B cells whereas cyclin D3 protein was only detected in GC cells and previous reports showing that cyclin D3 was regulated by pre-BCR mediated inhibition of proteosomal degradation (7) we hypothesized that GC-specific signaling events promote cyclin D3 protein stability. The proteosomal degradation of D-type cyclins upon phosphorylation of a conserved threonine residue by GSK3α/β has been previously reported (10). In addition phosphorylation of GSK3α/β on serine 21/9 residues leads to reduced kinase activity (27). We ...
The generation of robust T-cell-dependent humoral immune responses requires the formation and expansion of germinal center structures within the follicular regions of the secondary lymphoid tissues. was only observed in mature GCs (Fig. ?(Fig.5D).5D). These data correlate with the lack of cyclin D2 manifestation in adult GCs and the requirement for cyclin D3 specifically at this stage. Based on our observation that cyclin D3 transcripts were observed in both follicular and GC B cells whereas cyclin D3 protein was only detected in GC cells and previous reports showing that cyclin D3 was regulated by pre-BCR mediated inhibition of proteosomal degradation (7) we hypothesized that GC-specific signaling events promote cyclin D3 protein stability. The proteosomal degradation of D-type cyclins upon phosphorylation of a conserved threonine residue by GSK3α/β has been previously reported (10). In addition phosphorylation of GSK3α/β on serine 21/9 residues leads to reduced kinase activity (27). We ...
View mouse Ccndbp1 Chr2:121008403-121016904 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
Cyclin D1 is an important cell cycle regulator but in cancer its overexpression also increases cellular migration mediated by p27KlP1 stabilization and RhoA inhibition. Recently, a common polymorphism at the exon 4-intron 4 boundary of the human cyclin D1 gene within a splice donor region was associated with an altered risk of developing cancer. Altered RNA splicing caused by this polymorphism gives rise to a variant cyclin D1 isoform termed cyclin D1b, which has the same N-terminus as the canonical cyclin D1a isoform but a distinct C-terminus. In this study we show that these different isoforms have unique properties with regard to the cellular migration function of cyclin D1. Whereas they displayed little difference in transcriptional co-repression assays on idealized reporter genes, microarray cDNA expression analysis revealed differential regulation of genes including those that influence cellular migration. Additionally, while cyclin D1a stabilized p27KIP1 and inhibited RhoA-induced ROCK kinase
TY - JOUR. T1 - Interaction between the pRb2/p130 C-terminal domain and the N-terminal portion of cyclin D3. AU - Bonetto, Francesco. AU - Fanciulli, Maurizio. AU - Battista, Tullio. AU - De Luca, Antonio. AU - Russo, Patrizia. AU - Bruno, Tiziana. AU - De Angelis, Roberta. AU - Di Padova, Monica. AU - Giordano, Antonio. AU - Felsani, Armando. AU - Paggi, Marco C.. PY - 1999/12/15. Y1 - 1999/12/15. N2 - An association between cyclin D3 and the C-terminal domain of pRb2/p130 was demonstrated using the yeast two-hybrid system. Further analysis restricted the epitope responsible for the binding within the 74 N-terminal amino acids of cyclin D3, independent of the LXCXE amino acid motif present in the D-type cyclin N-terminal region. In a coprecipitation assay in T98G cells, a human glioblastoma cell line, the C-terminal domain of pRb2/p130 was able to interact solely with cyclin D3, while the corresponding portion of pRb interacted with either cyclin D3 or cyclin D1. In T98G cells, endogenous ...
The protein encoded by the Bcl-1 oncogene, known as cyclin D1, belongs to the highly conserved family of cyclin-dependent kinase (CDK) regulators. It is also known as CCND1, B-cell lymphoma 1 protein (BCL1), parathyroid adenomatosis 1 (PRAD1), B-cell CLL/lymphoma 1, G1/S-specific cyclin-D1, D11S287E, and U21B31. Different cyclins exhibit distinct expression and degradation patterns that contribute to the coordination of the cell cycle during mitosis. Cyclin D1 interacts with CDK4 and CDK6, whose activity is required for the cell cycle G1/S transition. Cyclin D1 also interacts with tumor suppressor protein Rb. Mutations in the Bcl-1 gene are associated with a variety of cancers, including esophageal, breast, and bladder cancer, as well as a variety of B-cell-related leukemias and lymphomas.. ...
and a shift of cyclin D1 mRNA from the polysome-associated to free mRNA fraction, indicating that 15d-PGJ2 inhibits the initiation of cyclin D1 mRNA translation. The selective rapid decrease in cyclin D1 protein accumulation is facilitated by its rapid turnover (t1/2=34 min) after inhibition of cyclin D1 protein synthesis. The half-life of cyclin D1 protein is not significantly altered in cells treated with 15d-PGJ2. Treatment of cells with 15d-PGJ2 results in strong induction of heat shock protein 70 (HSP70) gene expression, suggesting that 15d-PGJ2 might activate protein kinase R (PKR), an eIF- ...
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 ...
购买经敲除验证的重组Cyclin D1兔单克隆抗体[EP272Y](ab40754),Cyclin D1抗体经WB,IP验证,可与人,小鼠,大鼠样本反应。8篇文献引用,4个独立用户反馈。
Cyclin D1 expression is induced by Sox17.(A-B) Immunohistochemistry for cyclin D1 was performed on lung sections from adult CCSPrtTA (A) and CCSPrtTA/tetO-Sox
Cyclin D1 is a target for positive regulation by estrogens in growth-responsive cells, in which it mediates their mitogenic effects. Amplification and overexpression of the cyclin D1 gene (CCND1) might thus represent a genetic lesion inducing hormone-independent growth of transformed cells. Indeed, cyclin D1 overexpression has been found in up to 50% of primary breast cancers, and in about one-third of these cases, this is linked to amplification of the 11q13 chromosomal region, which also includes the CCND1 gene. These tumors are predominantly estrogen receptor-positive, and for this reason, these patients are often selected for adjuvant antiestrogen therapy. No information is available, however, as to whether cyclin D1 overexpression due to gene amplification might interfere with and reduce antiestrogen efficacy. This was investigated here by taking advantage of an experimental model that reproduces cyclin D1 overexpression resulting from increased CCND1 gene dosage in hormone-responsive human ...
Sabath, D.F.; Drachman, J.G.; Kaushansky, K.; Broudy, V.C., 1994: Development of a cell line dependent on MPL ligand for proliferation
Call (314) 361-4242 :: According to the American Academy of Orthopaedic Surgeons car crashes are one of the most common causes of spinal fractures.
In contrast to cyclin D1 and D2, the expression level of cyclin D3 was high in the hindbrain at the E15.5 stage (Figure 3I, arrowhead). Moreover, in the midbrain cyclin D3 was expressed in cells closer to the ventricle than those expressing cyclin D2 (Figure 3H, I, arrows).. Discussion. At the E10.5 stage, all three D-type cyclins were expressed in most of the spinal cord cells but cyclin D1 and D3 showed higher expression levels in the dorsal half of the spinal cord. Wianny et al. (1998) found that the dorso-ventral gradient of the cyclin D1 transcript also occurs in the spinal cord of 7-9 somite-stage embryos. However, in our study we found that at the E10.5 stage cyclin D2 was not missing from the floor plate and also that cyclin D3 was not expressed only ventrally, as was reported for the transcripts of the genes in 7-9 somite stage embryos by Wianny et al. (1998). This may have been due to altered expression patterns of these genes during the time course of spinal cord development and ...
Expression profile and molecular genetic regulation of cyclin D1 expression in epithelioid sarcoma Epithelioid sarcoma is a distinctive, aggressive soft tissue tumor typically presenting as a subcutaneous or deep dermal mass in the distal extremities of young adults. Molecular genetic data of well-characterized cases of epithelioid sarcoma are sparse. A recent cytogenetic study of epithelioid sarcoma by conventional metaphase comparative genomic hybridization reported recurrent gains at chromosome 11q13, a region containing many genes, including the cyclin D1 gene. Cyclin D1 is a positive cell cycle regulator that is overexpressed in a variety of neoplasms, including mantle cell lymphoma and breast carcinoma. The objective of this study was to examine cyclin D1 expression in epithelioid sarcoma. Of 24 cases evaluated, 23 (96%) displayed cyclin D1 nuclear expression using immunohistochemical evaluation. Eight cases, which expressed cyclin D1 by immunohistochemistry, were evaluated by fluorescence ...
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 ...
As described above, we have reported a new physiological function of Cyclin D2 in the neuronal development of the mouse. We next questioned whether this mechanism is conserved among mammalian species. In humans, we found an accumulation of Cyclin D2 protein at the basal side of the cortical primordium at gestation week 16 (Tsunekawa et al. 2012). We also noted that the cis-acting element identified in mice that promotes basal transportation is highly conserved in human (74% match in the National Center for Biotechnology Information [NCBI] database). Therefore, it is tempting to speculate that in the human cortical primordium, Cyclin D2 mRNA is similarly transported within the basal process toward the basal endfoot and locally translated into protein. Notably, the basal transport cis-element that we have identified appears to be unique to mammals, as similar sequences are not found in avians or amphibians (NCBI database). Similarly, no accumulation of Cyclin D2 mRNA in the basal side of the chick ...
...(PHILADELPHIA) Cyclin D1 a protein that helps push a replicating cel... In addition to its role in regulating the cell cycle cyclin D1 induc...Using antisense RNA Dr. Pestells group was the first to show that cy...In the current study the group sought to investigate the mechanism by...,Cyclin,D1,governs,microRNA,processing,in,breast,cancer,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
Smad nuclear interacting protein 1 (SNIP1) is an evolutionarily conserved protein containing a forkhead-associated (FHA) domain that regulates gene expression through interactions with multiple transcriptional regulators. Here, we have used short interfering RNAs (siRNAs) to knockdown SNIP1 expression in human cell lines. Surprisingly, we found that reduction in SNIP1 levels resulted in significantly reduced cell proliferation and accumulation of cells in the G1 phase of the cell cycle. Consistent with this result, we observed that cyclin D1 protein and mRNA levels were reduced. Moreover, SNIP1 depletion results in inhibition of cyclin D1 promoter activity in a manner dependent upon a previously characterized binding site for the AP-1 transcription factor family. SNIP1 itself is induced upon serum stimulation immediately prior to cyclin D1 expression. These effects were independent of the tumour suppressors p53 and retinoblastoma (Rb), but were consistent with an interaction with BRG1, a component of
The cyclin D1 expression pattern is not altered by signaling inhibitors. If the PI3K/AKT/GSK3 pathway stabilizes cyclin D1 levels specifically during G1 and G2 phases as suggested above, inhibitors of this pathway would produce a reduction in cyclin D1 expression during these cell cycle phases to the low levels seen during S phase. Thus, inhibition of these signaling pathways would be expected to result in low, uniform expression of cyclin D1 throughout the cell cycle. PI3K was inhibited by LY294002, while the kinase mTOR was inhibited by rapamycin in actively cycling human diploid fibroblast (MRC5) cultures. After 2 hrs treatment, including a terminal pulse with BrdU, the culture was fixed and stained with fluorescent antibodies against both cyclin D1 and BrdU, while DNA was stained with DAPI. Individual images of each fluorochrome were collected with a sensitive CCD camera, and subjected to image analysis to accurately quantitate the level of each fluorochrome in each cell (see [20]). The ...
We report several novel observations. First, we find that multiple cdk4/6 and D-cyclin combinations can robustly stimulate human β-cell replication in vitro. Surprisingly, among all of the possible cdk4/6-D-cyclin combinations, cyclin D3 appeared to be a particularly effective partner for cdk6 and cdk4. Second, we demonstrate that, although cyclin D2 is a very effective partner for both cdk4 and cdk6 in stimulating human β-cell replication, and despite its being both present and essential for rodent β-cell replication and function, it is only marginally detectable in human β-cells. Third, we observe that the D-cyclins and cdks 4 and 6 are principally cytosolic proteins in the human β-cell. Fourth, we report that a single member of the cdk4/6 D-cyclin complex, cdk6, is able to enhance human β-cell transplantation in vivo. Fifth, we demonstrate that human β-cell replication can be sustained in vivo for at least four weeks using cdk6.. The rapid proliferation induced by the D3 combinations ...
Citation: Soni R. and Chaudhuri B. (2001) Cell cycle arrest mediated by a pyridopyrimidine is not abrogated by over-expression of Bcl-2 and cyclin D1. International Journal of Oncology. 18 (5) pp.1035-40 ...
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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 ...
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 ...
Mouse Monoclonal Anti-Cyclin D1 Antibody (DCS-6). G1-Cyclin & Mantle Cell Marker. Validated: WB, ELISA, Flow, ICC/IF, IHC-Fr, IHC-P, IP, PAGE. Tested Reactivity: Human, Mouse, Rat, and more. 100% Guaranteed.
Monoclonal clone# G2 antibody for CYCLIN D2/CCND2 detection. Host: Mouse.Size: 100μg/vial. Tested applications: ICC. Reactive species: Human. CYCLIN D2/CCND2 information: Molecular Weight: 32826 MW; Subcellular Localization: Nucleus . Cytoplasm . Membran
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Proliferation is accelerated in GSK3β inhibitor treated mice compared to similarly injured, but vehicle treated micea) Cyclin D1, c-myc and β-catenin levels b
ATACAGGAAG TGACGATACT TTTGGCGCGC GCGGTTGCTG TTTCTTCTCT GGCTCCGGGA CCGGCGGCGG CGGCGGCGGC ACGGGCGGCG GCGTAGGGTG ^1 ^11 ^21 ^31 ^41 ^51 ^61 ^71 ^81 ^91 TTTTAACTCA AATGGGTGAT GAAAAGGACT CTTGGAAAGT GAAAACTTTA GATGAAATTC TTCAGGAAAA GAAACGAAGG AAGGAACAAG AGGAGAAAGC ^101 ^111 ^121 ^131 ^141 ^151 ^161 ^171 ^181 ^191 AGAGATAAAA CGCTTAAAAA ATTCTGATGA CCGGGATTCC AAGCGGGATT CCCTTGAGGA GGGGGAGCTG AGAGATCACT GCATGGAGAT CACAATAAGG ^201 ^211 ^221 ^231 ^241 ^251 ^261 ^271 ^281 ^291 AACTCCCCGT ATAGAAGAGA AGACTCTATG GAAGACAGAG GAGAAGAAGA TGATTCTTTG GCCATCAAAC CACCCCAGCA AATGTCTCGG AAAGAAAAAG ^301 ^311 ^321 ^331 ^341 ^351 ^361 ^371 ^381 ^391 TTCATCACAG AAAAGATGAA AAGAGAAAAG AGAAAAAGCA TGCTAGAGTG AAGAAGAAAG AAAGAGAGCA CGAACGTCGG AAACGACATC GAGAAGAACA ^401 ^411 ^421 ^431 ^441 ^451 ^461 ^471 ^481 ^491 GGATAAAGCT CGCCGGGAAT GGGAAAGACA GAAGAGAAGG GAAATGGCAA GGGAGCATTC CAGGAGAGAA AGGGGGAATG ATGGCGTGTG CCTCTTCAGG ^501 ^511 ^521 ^531 ^541 ^551 ^561 ^571 ^581 ^591 GACCGCTTGG AGCAGTTAGA AAGGAAGCGG GAGCGGGAGC GCAAGATGCG ...
Cyclin D1 and p16 are involved in the regulation of G1 checkpoint and may play an important role in the tumorigenesis of nasopharyngeal carcinoma (NPC). Previous studies have examined the level of expression of cyclin D1 and p16 in primary untreated NPC but no such information is available for recurrent NPC. We set out in this study to examine the expression level of cyclin D1 and p16 in recurrent NPC that have failed previous treatment with radiation +/- chemotherapy. A total of 42 patients underwent salvage nasopharyngectomy from 1984 to 2001 for recurrent NPC after treatment failure with radiation +/- chemotherapy. Twenty-seven pathologic specimens were available for immunohistochemical study using antibodies against cyclin D1 and p16. Positive expression of cyclin D1 was observed in 7 of 27 recurrent NPC specimens (26%) while positive p16 expression was seen in only 1 of 27 recurrent NPC (4%). While the level of expression of cyclin D1 in recurrent NPC was similar to that of previously untreated
Cyclin D1 and p16 are involved in the regulation of G1 checkpoint and may play an important role in the tumorigenesis of nasopharyngeal carcinoma (NPC). Previous studies have examined the level of expression of cyclin D1 and p16 in primary untreated NPC but no such information is available for recurrent NPC. We set out in this study to examine the expression level of cyclin D1 and p16 in recurrent NPC that have failed previous treatment with radiation +/- chemotherapy. A total of 42 patients underwent salvage nasopharyngectomy from 1984 to 2001 for recurrent NPC after treatment failure with radiation +/- chemotherapy. Twenty-seven pathologic specimens were available for immunohistochemical study using antibodies against cyclin D1 and p16. Positive expression of cyclin D1 was observed in 7 of 27 recurrent NPC specimens (26%) while positive p16 expression was seen in only 1 of 27 recurrent NPC (4%). While the level of expression of cyclin D1 in recurrent NPC was similar to that of previously untreated
The present study was conducted to analyze the alterations affecting cyclins D1, E, and A in bilharzial bladder cancer and to assess their potential clinical significance. A total of 125 cases were examined. Histopathological subtypes included 68 squamous cell carcinomas, 55 transitional cell carcinomas, and 2 adenocarcinomas. Immunohistochemical analyses were performed using a panel of well-characterized antibodies. The results were correlated with proliferative index, as assessed by Ki67 antigen expression. The cyclin D1-positive phenotype, defined as the identification of positive immunoreactivity in the nuclei of ,/=20% of tumor cells, was found in 33 of 107 (31%) evaluable cases. A significant association was observed between the cyclin D1-positive phenotype and deep muscle invasion (P = 0.02), high tumor grade (P = 0.02), and Ki67 high proliferative index (P = 0.03). The cyclin E-positive phenotype, defined as per cyclin D1, was found in 79 of 106 (75%) evaluable cases. The cyclin ...
Aberrant expression of cyclin D1, frequently observed in human malignant disorders, has been linked to the control of G1→S cell cycle phase transition and development and progression in carcinogenesis. Cyclin D1 level changes are partially controlled by GSK-3β-dependent phosphorylation at threonine-286 (Thr286), which targets cyclin D1 for ubiquitination and proteolytic degradation. In our continuing studies on the mechanism of prostate cancer prevention by resveratrol, focusing on the role of its recently discovered target protein, quinone reductase 2 (NQO2), we generated NQO2 knockdown CWR22Rv1 using short hairpin RNA (shRNA)-mediated gene silencing approach. We found that, compared with cells expressing NQO2 (shRNA08), NQO2 knockdown cells (shRNA25) displayed slower proliferation and G1 phase cell accumulation. Immunoblot analyses revealed a significant decrease in phosphorylation of retinoblastoma Rb and cyclin D1 in shRNA25 compared with shRNA08. Moreover, shRNA25 cells showed a 37% ...
Changes to cell cycle-regulating machinery that occur during differentiation of cells are thought to be responsible mostly for withdrawal from cycling. Here, embryonal carcinoma (EC) cell lines were found that differ in their basal levels of p27 inhibitor of cyclin-dependent kinases but not in their growth rates, distribution of cells in phases of cell cycle, and their ability to differentiate. High basal levels of p27 did not substitute for up-regulation of p27 that in EC cells normally occurs early after entering a differentiation pathway. Under both standard and differentiation-supporting culture conditions, variances in the levels of p27 were strictly followed by variances in the levels of cyclins D2 and D3. In EC cells genetically manipulated to overexpress p27 protein, cyclin D3 became up-regulated and vice versa. Supposedly, titration of p27 by D-type cyclins, which prevents its inhibitory action toward cyclin-dependent kinase 2, allows for the maintenance of elevated p27 in proliferating ...
Chromosomal instability (CIN) in tumors is characterized by chromosomal abnormalities and an altered gene expression signature; however, the mechanism of CIN is poorly understood. CCND1 (which encodes cyclin D1) is overexpressed in human malignancies and has been shown to play a direct role in transcriptional regulation. Here, we used genome-wide ChIP sequencing and found that the DNA-bound form of cyclin D1 occupied the regulatory region of genes governing chromosomal integrity and mitochondrial biogenesis. Adding cyclin D1 back to Ccnd1-/- mouse embryonic fibroblasts resulted in CIN gene regulatory region occupancy by the DNA-bound form of cyclin D1 and induction of CIN gene expression. Furthermore, increased chromosomal aberrations, aneuploidy, and centrosome abnormalities were observed in the cyclin D1-rescued cells by spectral karyotyping and immunofluorescence. To assess cyclin D1 effects in vivo, we generated transgenic mice with acute and continuous mammary gland-targeted cyclin D1 ...
The relative levels of cyclin D1 (CCND1) (a) and (b) transcripts were determined by real-time reverse transcription polymerase chain reaction (RT-PCR) and found to vary according to the tissue origin in both control and tumor samples. A five-fold overexpression of both isoforms was observed in 28/38 cases of mantle cell lymphoma (MCL) and of only one isoform in 10/38 MCL. No correlation was observed between expression of cyclin D1 isoforms and CCND1 genotype at position 870. ...
B78 Growth arrest represents an innate barrier to carcinogenesis. DNA damage and replicational stress are known to induce growth arrest and apoptotic death to avert genomic instability and consequently carcinogenesis. Working on the genotoxic stress induced by hydroxyurea and methylmethanesulfone, we observed a growth arrest at G1/S-phase that was mediated by destabilization of cyclin D1. The growth arrest was independent of the stability of cdc25A and preceded transcriptional up-regulation of p21waf1. Cyclin D1 destabilization involved its phosphorylation by GSK-3beta at threonine-286 since overexpression of the kinase-dead mutant of GSK-3beta or cyclin D1T286A mutant conferred stability to cyclin D1. Further, overexpression of cyclin D1T286A also helped in bypassing G1/S phase growth arrest. We also observed a rapid inactivation of Akt/PKB kinase in the presence of hydroxyurea. Enforced expression of the constitutively active Akt or viral oncoprotein HBx was sufficient to overcome growth ...
Activation of growth factor receptors by ligand binding initiates a cascade of events leading to cell growth and division. Progression through the cell cycle is controlled by cyclin-dependent protein kinases (Cdks), but the mechanisms that link growth factor signaling to the cell cycle machinery have not been established. We report here that Ras proteins play a key role in integrating mitogenic signals with cell cycle progression through G1. Ras is required for cell cycle progression and activation of both Cdk2 and Cdk4 until approximately 2 h before the G1/S transition, corresponding to the restriction point. Analysis of Cdk-cyclin complexes indicates that Ras signaling is required both for induction of cyclin D1 and for downregulation of the Cdk inhibitor p27KIP1. Constitutive expression of cyclin D1 circumvents the requirement for Ras signaling in cell proliferation, indicating that regulation of cyclin D1 is a critical target of the Ras signaling cascade. ...
Although it has been reported to contain high polyphenols, the pharmacological studies of the calyx of Diospyros kaki Thunb (DKC) have not been elucidated in detail. In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells. Anti-cell proliferative effect of 70% ethanol extracts from the calyx of Diospyros kaki (DKC-E70) was evaluated by MTT assay. The effect of DKC-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. DKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of
Severe and prolonged cytopenias represent a considerable problem in clinical stem cell transplantations. Cytokine-induced ex vivo expansion of hematopoietic stem and progenitor cells has been intensively explored as a means of accelerating hematopoietic recovery following transplantation but have so far had limited success. Herein, overexpression of D-type cyclins, promoting G0/G1 to S transition, was investigated as an alternative approach to accelerate myeloid reconstitution following stem cell transplantation. With the use of retroviral-mediated gene transfer, cyclin D2 was overexpressed in murine bone marrow progenitor cells, which at limited doses showed enhanced ability to rescue lethally ablated recipients. Competitive repopulation studies demonstrated that overexpression of cyclin D2 accelerated myeloid reconstitution following transplantation, and, in agreement with this, cyclin D2-transduced myeloid progenitors showed an enhanced proliferative response to cytokines in vitro. Furthermore,
Although mutations that activate the Hedgehog (Hh) signalling pathway have been linked to several types of cancer, the molecular and cellular basis of Hhs ability to induce tumour formation is not well understood. We identified a mutation in patched (ptc), an inhibitor of Hh signalling, in a genetic screen for regulators of the Retinoblastoma (Rb) pathway in Drosophila. Here we show that Hh signalling promotes transcription of Cyclin E and Cyclin D, two inhibitors of Rb, and principal regulators of the cell cycle during development in Drosophila. Upregulation of Cyclin E expression, accomplished through binding of Cubitus interruptus (Ci) to the Cyclin E promoter, mediates the ability of Hh to induce DNA replication. Upregulation of Cyclin D expression by Hh mediates the distinct ability of Hh to promote cellular growth. The discovery of a direct connection between Hh signalling and principal cell-cycle regulators provides insight into the mechanism by which deregulated Hh signalling promotes ...
Cyclins are key regulators of the cell cycle in all eukaryotes. We have previously isolated two B-type cyclin genes, cycMs1 and cycMs2, from alfalfa that are primarily expressed during the G2-to-M phase transition and are most likely mitotic cyclin genes. Here, we report the isolation of a novel alfalfa cyclin gene, termed cycMs3 (for cyclin Medicago sativa), by selecting for mating type alpha-pheromone-induced cell cycle arrest suppression in yeast. The central region of the predicted amino acid sequence of the cycMs3 gene is most similar to the cyclin box of yeast B-type and mammalian A- and B-type cyclins. In situ hybridization showed that cycMs3 mRNA can be detected only in proliferating cells and not in differentiated alfalfa cells. When differentiated G0-arrested cells were induced to reenter the cell cycle in the G1 phase and resume cell division by treatment with plant hormones, cycMs3 transcript levels increased long before the onset of DNA synthesis. In contrast, histone H3-1 mRNA and ...
Kanker payudara adalah penyakit penyebab kematian yang tinggi di dunia. Salah satu aktivitas yang abnormal terjadi karena Cyclin-D pada tahap siklus sel. Alternatif pengobatan menggunakan umbi keladi tikus yang mengandung asam linoleat. Tujuan penelitian untuk mengetahui ekspresi Cyclin-D pada cell-line kanker payudara T47D dengan perlakuan ekstrak umbi keladi tikus (Typhonium Flagelliforme). Jenis penelitian dengan Post Test Only Control Group Design. Menggunakan subjek penelitian cell-line kanker payudara T47D yang telah confluence 80 % dibagi menjadi 4 kelompok. Kelompok I: sebagai kontrol, Kelompok II : dosis 29,075 µg/ml; kelompok III: dosis 58, 151 µg/ml dan kelompok IV: dosis 116,302 µg/ml. Rerata Ekspresi Cyclin-D dianalisis dengan oneway-Anova dilanjutkan uji Post Hoc LSD (Least Significant Difference). Hasil rerata prosentase ekspresi Cyclin-D kelompok kontrol = 18,20%; kelompok dosis 29,075 = 7,66 %; kelompok dosis 58,151 = 3,33 %; kelompok dosis 116,302 = 6,93 %. Hasil uji ...
NU6102, CDK1/cyclin B and CDK2/cyclin A3 inhibitor (CAS 444722-95-6), with |98% purity. Join researchers using our high quality biochemicals.
The cyclin E oncogene activates CDK2 to drive cells from G1 to S phase of the cell cycle to commence DNA replication. It coordinates essential cellular functions with the cell cycle including histone biogenesis, splicing, centrosome duplication and origin firing for DNA replication. The two E-cyclins, E1 and E2, are assumed to act interchangeably in these functions. However recent reports have identified unique functions for cyclins E1 and E2 in different tissues, and particularly in breast cancer. Cyclins E1 and E2 localise to distinct foci in breast cancer cells as well as co-localising within the cell. Both E-cyclins are found in complex with CDK2, at centrosomes and with the splicing machinery in nuclear speckles. However cyclin E2 uniquely co-localises with NPAT, the main activator of cell-cycle regulated histone transcription. Increased cyclin E2, but not cyclin E1, expression is associated with high expression of replication-dependent histones in breast cancers. The preferential localisation of
The G1 cyclins, cyclin D1 and E, are rate limiting for progression through G1 phase of the cell cycle in breast epithelial cells and are oncogenic when expressed in the mammary epithelium of transgenic mice. These genes are frequently overexpressed in clinical breast cancer where overexpression appears to be associated with specific disease phenotypes, altered responsiveness to therapeutic intervention and patient survival. In order to investigate the functional correlates of cyclin D1 and cyclin E overexpression we employed a panel of normal, immortalized and neoplastic breast epithelial cell lines to examine the relationships between cyclin gene expression, cyclin-CDK complex formation and CDK activity. In agreement with earlier studies cyclin D1 and E expression varied over an approximately tenfold range among the 18 cell lines studied. There was no apparent relationship, however, between cyclin D1 expression and the in vitro activity of its major kinase partner, Cdk4, although MDA-MB-134 cells
B-cell lymphoma gene (BCL-6) upregulation contributes to immortalization of mouse embryo fibroblast and primary B cells via upregulation of cyclin D1. As cyclin D1 overexpression is a common phenomenon in different cancers, BCL-6 protein overexpression may not be restricted to lymphomas. In this study, expression of BCL-6 was investigated by immunohistochemistry on ... read more paraffin-embedded specimens from 150 breast cancer patients and 10 specimens of normal breast tissue. The results showed BCL-6 overexpression (X10% of cells) in 24/150 (16%) breast cancer patients, whereas in normal breast low expression (o1%) of BCL-6 was observed. In linear regression analysis BCL-6 expression was associated with cyclin D1 (r=0.197, P=0.016). Further, in v2 analyses, BCL-6-positivity was associated with overexpression of p53 (P=0.016), and hypoxia-inducible factor-1a (P,0.001). Involvement of BCL-6 in breast carcinogenesis is further underscored by comparative genomic hybridization analysis that showed ...
Malignant gliomas frequently show genetic aberrations of genes coding for cell cycle regulatory proteins involved in the control of G1/S phase transition. These include mutation and/or deletion of the retinoblastoma (RB1) gene, homozygous deletion of the CDKN2A and CDKN2B genes, as well as amplification and overexpression of the CDK4 and CDK6 genes. The D‐type cyclins (cyclin D1, D2, and D3) promote cell cycle progression from G1 to S phase by binding to and activating the cyclin dependent kinases Cdk4 and Cdk6. Here, we have investigated a series of 110 primary malignant gliomas and 8 glioma cell lines for amplification and expression of the D‐type cyclin genes CCND1 (11q13), CCND2 (12p13), and CCND3 (6p21). We found the CCND1 gene amplified and overexpressed in one anaplastic astrocytoma of our tumor series. Two glioblastomas and one anaplastic astrocytoma showed CCND2 gene amplification, but lacked significant overexpression of CCND2 transcripts. Amplification and overexpression of the ...
Breast cancer is one of the most common malignancies in women. Due to early detection and the use of screening programs approximately 60% of all new cases lack lymph node involvement. Today, a substantial proportion of these women will be offered adjuvant systemic chemotherapy. However, better proliferation markers are needed to predict patient outcome and to avoid overtreatment. Cyclin A, cyclin E and Ki-67 are all markers for proliferation and involved in the regulation of the cell cycle. Overexpression has been associated with disease recurrence in several studies, but the results have not been consistent. However, none of these studies has investigated aberrant expression of cyclin E (the expression of cyclin E during phases of the cell cycle other than late G1 and early S-phase). Studies have shown that aberrant cyclin E might provide additional prognostic information compared to cyclin E alone.. The aims of this thesis were 1.to investigate the prognostic value of cyclin A, cyclin E and ...
The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of cyclin-dependent kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. Knockout studies of the homologous gene in mouse suggest the essential roles of this gene in ovarian granulosa and germ cell proliferation. High level expression of this gene was observed in ovarian and testicular tumors.[2] ...
Using two endometrial cancer cell lines, IL11Rα blockade reduced IL11 action, but there was a blunted functional response in grade 1 Ishikawa endometrial cancer-derived cells compared with grade 2 HEC1A cells, likely due to differences in IL11 ligand production and/or IL11Rα expression levels between the cell lines. IL11Rα blockade only transiently reduced Ishikawa cell proliferation in vitro and tumor growth in vivo. When protein levels of cyclin D3 were determined, hIL11Rα antibody treatment downregulated this established IL11-regulated cell-cycle target (21,25) in HEC1A tumors compared with IgG control. However, there was no effect of IL11Rα inhibition on cyclin D3 levels in Ishikawa tumors. This finding coincided with a more profound reduction in HEC1A cell proliferation in response to IL11 blockade in vitro, compared with Ishikawa cells. Both Ishikawa and HEC1A cells are responsive to exogenous IL11, as shown previously by STAT3 activation (22). However, as Ishikawa cells endogenously ...
Ribociclib is an orally available cyclin-dependent kinase (CDK) inhibitor targeting cyclin D1/CDK4 and cyclin D3/CDK6 cell cycle pathway, with potential antineoplastic activity. Actually, this agent is in Phase III study to treat hormone receptor-positive in certain types of cancer. We report a side effect of this new drug to include in the list of etiology of Cornea Verticillata ...
PURPOSE: We analyzed the expression of critical cell cycle regulators cyclin E and cyclin D1 in familial breast cancer, focusing on BRCA mutation-negative tumors. Cyclin E expression in tumors of BRCA1 or BRCA2 carriers is higher, and cyclin D1 expression lower, than in sporadic tumors. In familial non-BRCA1/2 tumors, cyclin E and cyclin D1 expression has not been studied. EXPERIMENTAL DESIGN: Cyclin E and cyclin D1 immunohistochemical expression was studied in tissue microarrays consisting of 53 BRCA1, 58 BRCA2, 798 familial non-BRCA1/2, and 439 sporadic breast tumors. RESULTS: In univariate analysis, BRCA1 tumors had significantly more frequently high cyclin E (88%) and low cyclin D1 (84%) expression than sporadic (54% and 49%, respectively) or familial non-BRCA1/2 (38% and 45%, respectively) tumors. BRCA2 tumors had significantly more frequently low cyclin D1 expression (68%) than sporadic or familial non-BRCA1/2 tumors and significantly more frequently high cyclin E expression than familial ...
Recent advances in defining the molecular mechanisms of cell cycle control in eukaryotes provide a basis for better understanding the hormonal control of cell proliferation in normal and neoplastic breast epithelium. It is now clear that a number of critical steps in cell cycle progression are controlled by families of serine/threonine kinases, the cdks. These kinases are activated by interactions with various cyclin gene products which form the regulatory subunits of the kinase complexes. Several families of cyclins control cell cycle progression in G1 phase, cyclins C, D and E, or in S, G2 and mitosis, cyclins A and B. Recent studies have defined the expression and regulation of cyclin genes in normal breast epithelial cells and in breast cancer cell lines. Following growth arrest of T-47D breast cancer cells by serum deprivation restimulation with insulin results in sequential induction of cyclin genes. Cyclin D1 mRNA increases within 1 h of mitogenic stimulation and is followed by increased
We report the isolation of UME3, a C‐type cyclin that is required for the full repression of several early meiotic genes (e.g. SPO13) and SSA1, a member of the HSP70 superfamily. Similarly to other cyclin C family members, UME3 mRNA and protein levels remained unchanged throughout the mitotic cell cycle. However, under conditions that induce SSA1 or SPO13 transcription, we demonstrate that Ume3p is subjected to degradation. This destruction is required for normal meiotic gene induction, as a mutation that stabilizes Ume3p resulted in a 2‐fold reduction in SPO13 mRNA accumulation. These findings reveal the first observed regulation of a C‐type cyclin. Moreover, the destruction of Ume3p in response to heat shock or developmental cues represents a new set of regulatory signals by which any cyclin is controlled. We identified three cis‐acting domains (PEST‐rich, RXXL and the cyclin box) that contribute to the destruction of Ume3p during heat shock. In cultures exposed to heat shock, Ume3p ...
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 ...
Pathogenic remodeling following heart injury is due, in part, to the limited regenerative capacity of adult cardiomyocytes. Cell cycle induction has been recently explored as a therapeutic approach for heart failure, and to this end, expression of cyclin D2 in cardiomyocytes improves outcomes in mouse models follwoing myocardial infarction. In this episode, Gerd Hasenfuß, Loren Field, and Karl Toischer discuss their collaborative effort to further evaluate the effect of increased cyclin D2 on outcomes in response to other forms of heart failure. Cyclin D2 expression improved survival and cardiac function in mice exposed to pressure overload; however, cyclin D2-espressing mice were not protected from adverse effects in response to chronic volume overload. These results support further effort into the development of strategies to improve cardiomyocyte proliferation for some types cardiac injury.. ...
The transcription factor GATA-2 is critical regulator of hematopoietic stem and progenitor cell (HSPC) development and function, and mutations in the enhancer region of GATA2 are linked to blood disorders. In this episode, Emery Bresnick and colleagues develop and characterize a mouse model that harbors a human disease-associated GATA2 enhancer mutation. In this model, hematopoietic development and function were normal unless the animals were exposed to a secondary stress that necessitated blood cell regeneration. The results of this study provide important insight into GATA-2-dependent pathogenesis.. ...
Pathogenic remodeling following heart injury is due, in part, to the limited regenerative capacity of adult cardiomyocytes. Cell cycle induction has been recently explored as a therapeutic approach for heart failure, and to this end, expression of cyclin D2 in cardiomyocytes improves outcomes in mouse models follwoing myocardial infarction. In this episode, Gerd Hasenfuß, Loren Field, and Karl Toischer discuss their collaborative effort to further evaluate the effect of increased cyclin D2 on outcomes in response to other forms of heart failure. Cyclin D2 expression improved survival and cardiac function in mice exposed to pressure overload; however, cyclin D2-espressing mice were not protected from adverse effects in response to chronic volume overload. These results support further effort into the development of strategies to improve cardiomyocyte proliferation for some types cardiac injury.. ...
Pathogenic remodeling following heart injury is due, in part, to the limited regenerative capacity of adult cardiomyocytes. Cell cycle induction has been recently explored as a therapeutic approach for heart failure, and to this end, expression of cyclin D2 in cardiomyocytes improves outcomes in mouse models follwoing myocardial infarction. In this episode, Gerd Hasenfuß, Loren Field, and Karl Toischer discuss their collaborative effort to further evaluate the effect of increased cyclin D2 on outcomes in response to other forms of heart failure. Cyclin D2 expression improved survival and cardiac function in mice exposed to pressure overload; however, cyclin D2-espressing mice were not protected from adverse effects in response to chronic volume overload. These results support further effort into the development of strategies to improve cardiomyocyte proliferation for some types cardiac injury.. ...
Pathogenic remodeling following heart injury is due, in part, to the limited regenerative capacity of adult cardiomyocytes. Cell cycle induction has been recently explored as a therapeutic approach for heart failure, and to this end, expression of cyclin D2 in cardiomyocytes improves outcomes in mouse models follwoing myocardial infarction. In this episode, Gerd Hasenfuß, Loren Field, and Karl Toischer discuss their collaborative effort to further evaluate the effect of increased cyclin D2 on outcomes in response to other forms of heart failure. Cyclin D2 expression improved survival and cardiac function in mice exposed to pressure overload; however, cyclin D2-espressing mice were not protected from adverse effects in response to chronic volume overload. These results support further effort into the development of strategies to improve cardiomyocyte proliferation for some types cardiac injury.. ...
Pathogenic remodeling following heart injury is due, in part, to the limited regenerative capacity of adult cardiomyocytes. Cell cycle induction has been recently explored as a therapeutic approach for heart failure, and to this end, expression of cyclin D2 in cardiomyocytes improves outcomes in mouse models follwoing myocardial infarction. In this episode, Gerd Hasenfuß, Loren Field, and Karl Toischer discuss their collaborative effort to further evaluate the effect of increased cyclin D2 on outcomes in response to other forms of heart failure. Cyclin D2 expression improved survival and cardiac function in mice exposed to pressure overload; however, cyclin D2-espressing mice were not protected from adverse effects in response to chronic volume overload. These results support further effort into the development of strategies to improve cardiomyocyte proliferation for some types cardiac injury.. ...
In humans, there are two A-type cyclins - an embryonic-specific cyclin A1 and a somatic cyclin A2. Cyclin A1 is only expressed in meiosis and very early embryos, whereas cyclin A2 is present in proliferating somatic cells
MAGNETIC SENSOR DEVICE - Provided is a magnetic sensor device capable of suppressing a variation in determination for detection or canceling of a magnetic field intensity, which is caused by noise generated from respective constituent elements included in the magnetic sensor device and external noise, to thereby achieve high-precision magnetic reading. The magnetic sensor device includes: a first D-type flip-flop and a second D-type flip-flop each having an input terminal connected to an output terminal of a comparator; an XOR circuit having a first input terminal and a second input terminal which are connected to an output terminal of the first D-type flip-flop and an output terminal of the second D-type flip-flop, respectively; a selector circuit; and a third D-type flip-flop having an input terminal connected to an output terminal of the selector circuit. The selector circuit includes: a first input terminal (A) and a second input terminal (B) which are connected to the output terminal of the ...
Cyclin F兔多克隆抗体(ab123601)可与人样本反应并经WB实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
J:171486 Rutter M, Wang J, Huang Z, Kuliszewski M, Post M, Gli2 influences proliferation in the developing lung through regulation of cyclin expression. Am J Respir Cell Mol Biol. 2010 May;42(5):615-25 ...
Rabbit polyclonal Cyclin D1 (phospho T286) antibody validated for WB, ELISA and tested in Human. Referenced in 1 publication. Immunogen corresponding to…
マウス・モノクローナル抗体 ab38 交差種: Ms,Rat,Hu 適用: WB,IP,IHC-P,IHC-Fr,Flow Cyt…Cyclin A2抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody…
Cyclin G1, 0.1 mg. Cyclins are the regulatory subunits of Cdc2 p34 and related cyclin-dependent kinases (Cdks) which play critical roles in the control of cell cycle progression.
... , Authors: Immacolata Vocca, Gianmarco Muzi, Francesca Pentimalli, Antonio Giordano. Published in: Atlas Genet Cytogenet Oncol Haematol.
... can be found mainly in the food of animal origin. These types of proteins are also called complete proteins because it contains all the essential amino acids. These proteins can be found in meat, chicken, fish, eggs, milk products. Some sorts of fish are advanced for our nutrition because, besides necessary proteins, they also contain a high concentration of fatty acids that prevent heart attack and stroke. Salmon, sardines, trout, and tuna are fish that contains eight times more omega 3 and omega six fatty acids than other fish.. ...
Despouy G, Bastie JN, Deshaies S, Balitrand N, Mazharian A, Rochette-Egly C, Chomienne C, Delva L (Feb 2003). "Cyclin D3 is a ... Despouy G, Bastie JN, Deshaies S, Balitrand N, Mazharian A, Rochette-Egly C, Chomienne C, Delva L (Feb 2003). "Cyclin D3 is a ... CRABP2 has been shown to interact with Cyclin D3. GRCh38: Ensembl release 89: ENSG00000143320 - Ensembl, May 2017 GRCm38: ...
2002). "Interaction of p58(PITSLRE), a G2/M-specific protein kinase, with cyclin D3". J. Biol. Chem. 277 (38): 35314-22. doi: ... CDC2L1 has been shown to interact with Cyclin D3. GRCh38: Ensembl release 89: ENSG00000248333 - Ensembl, May 2017 "Human PubMed ... 2004). "Cyclin L2, a novel RNA polymerase II-associated cyclin, is involved in pre-mRNA splicing and induces apoptosis of human ... 2004). "Characterization of cyclin L2, a novel cyclin with an arginine/serine-rich domain: phosphorylation by DYRK1A and ...
2001). "Induction and expression of cyclin D3 in human pancreatic cancer". Journal of Cancer Research and Clinical Oncology. ...
... has been shown to interact with Cyclin D3 and eIF3a. Eukaryotic initiation factor 3 (eIF3) ENSG00000282986 GRCh38: ... as a new interaction partner of cyclin D3". FEBS Letters. 573 (1-3): 139-46. doi:10.1016/j.febslet.2004.07.071. PMID 15327989. ... as a new interaction partner of cyclin D3". FEBS Letters. 573 (1-3): 139-46. doi:10.1016/j.febslet.2004.07.071. PMID 15327989. ...
Lin J, Jinno S, Okayama H (2001). "Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's ... cyclin-dependent protein serine/threonine kinase regulator activity. • protein binding. • ATP binding. • cyclin binding. • ... Zhang Q, Wang X, Wolgemuth DJ (1999). "Developmentally regulated expression of cyclin D3 and its potential in vivo interacting ... Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 ...
Wang, W.; Zhao, L. -J.; Tan, Y. -X.; Ren, H.; Qi, Z. -T. (2012). "MiR-138 induces cell cycle arrest by targeting cyclin D3 in ...
... has been demonstrated to interact with: Cyclin D3 DDX5, MCM2, MYCBP, and PRKAR2A. GRCh38: Ensembl release 89: ... 2004). "A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95". Biochem. J. 378 (Pt 2): 673-9. doi: ... "A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95". Biochem. J. 378 (Pt 2): 673-9. doi:10.1042/ ...
Notably, ribociclib seems to also have an inhibitory effect on Cyclin D3/CDK6 activity. G1 therapeutics also has a Cdk4/6 ... It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. In the G1 phase of the cell cycle, mammalian cells ... It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. Palbociclib was the first CDK4/6 inhibitor to be ... CDK4 and CDK6 complex with cyclin D to drive the phosphorylation of the retinoblastoma protein, Rb, which allows the cell to ...
Liu W, Sun M, Jiang J, Shen X, Sun Q, Liu W, Shen H, Gu J (2004). "Cyclin D3 interacts with human activating transcription ... "ATF5 increases cisplatin-induced apoptosis through up-regulation of cyclin D3 transcription in HeLa cells". Biochem. Biophys. ...
... has been shown to interact with: AKT1, CKS1B, Cyclin D3, Cyclin E1, Cyclin-dependent kinase 2, Cyclin-dependent kinase 4 ... 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 ... Zhang Q, Wang X, Wolgemuth DJ (1999). "Developmentally regulated expression of cyclin D3 and its potential in vivo interacting ...
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 ... Shanahan F, Seghezzi W, Parry D, Mahony D, Lees E (Feb 1999). "Cyclin E associates with BAF155 and BRG1, components of the ... Galaktionov K, Beach D (1992). "Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple ...
2006). "Identification of extracellular signal-regulated kinase 3 as a new interaction partner of cyclin D3". Biochem. Biophys ...
1996). "Alpha interferon suppresses the cyclin D3 and cdc25A genes, leading to a reversible G0-like arrest". Mol. Cell. Biol. ...
Hedberg Y, Ljungberg B, Roos G, Landberg G (May 2003). "Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma ...
Parnaik pointed towards a complex that formed between lamin A/C and cyclin D3 that played an important role in muscle cell ... Parnaik's research has also shown a relationship between lamin A/C and cyclin D3. From her research Dr. ... Mariappan, Indumathi (20 February 2007). "Identification of cyclin D3 as a new interaction partner of lamin A/C". Biochemical ...
Requirement for cyclin D3 in germinal center formation and function Cell Research 6:631-646 (2010) Faust, TW., Chang, EH., ...
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 ...
... induction of cyclin D3 and p21 expression". Gut. 46 (4): 507-514. doi:10.1136/gut.46.4.507. ISSN 0017-5749. PMID 10716680. ...
This was shown by knocking out HDAC7 in mice, which then resulted in increased levels of the cell cycle regulator, cyclin D3; ... cyclin D1. Overall, this study demonstrated that HDAC7 once again interacts with β-catenin to keep endothelial cells in a low ...
Despouy G, Bastie JN, Deshaies S, Balitrand N, Mazharian A, Rochette-Egly C, Chomienne C, Delva L (February 2003). "Cyclin D3 ... thyroid hormone and vitamin D3 signalling". Nature. 355 (6359): 446-9. doi:10.1038/355446a0. PMID 1310351. Kastner P, Perez A, ...
... cyclins D3 and E2, and cyclin-dependent kinases CDK4 and CDK6. p14ARF and p21CIPI CDK inhibitor expression are conversely ... in part through direct downregulation of cyclin D2 and cyclin E2. miR-26a also directly suppresses expression of estrogen ... 2011). "Tumor-specific expression of microRNA-26a suppresses human hepatocellular carcinoma growth via cyclin-dependent and - ...
The three homologues, called cyclin D1, cyclin D2, and cyclin D3 are expressed in most proliferating cells and the relative ... 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 ... The synthesis of cyclin D is initiated during G1 and drives the G1/S phase transition. Cyclin D protein is anywhere from 155 ( ...
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 ... differential signaling requirements for activation of assembled cyclin D3-cdk4 complexes in B-1 and B-2 lymphocyte subsets". ... "The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2". The ...
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 ... Cyclin-D1 is a protein that in humans is encoded by the CCND1 gene. The CCND1 gene encodes the cyclin D1 protein. The human ...
... has been shown to interact with: AKAP8, CDC2L1, CDKN1B, CRABP2, Cyclin-dependent kinase 4, Cyclin-dependent kinase 6 ... Brooks AR, Shiffman D, Chan CS, Brooks EE, Milner PG (1996). "Functional analysis of the human cyclin D2 and cyclin D3 ... "Cloning and characterization of human cyclin D3, a cDNA closely related in sequence to the PRAD1/cyclin D1 proto-oncogene". J. ... 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; 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 ...
Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase ... cyclin binding. • cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine ... p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin- ... "Entrez Gene: CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1)".. *^ Gartel AL, Radhakrishnan SK (May 2005). "Lost in ...
A Cyclin-dependent kinase 6 interacts with: CDKN2C, Cyclin D1, Cyclin D3, P16, PPM1B, and PPP2CA. Cell cycle, Mitosis, CDK, ... 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 ... In mammalian cells, cell cycle is activated by CDK6 in the early G1 phase through interactions with cyclins D1, D2 and D3. ...
Cyclin D3 has been shown to interact with: AKAP8, CDC2L1, CDKN1B, CRABP2, Cyclin-dependent kinase 4, Cyclin-dependent kinase 6 ... Brooks AR, Shiffman D, Chan CS, Brooks EE, Milner PG (1996). "Functional analysis of the human cyclin D2 and cyclin D3 ... "Cloning and characterization of human cyclin D3, a cDNA closely related in sequence to the PRAD1/cyclin D1 proto-oncogene". J. ... 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 ...
Rabbit polyclonal Cyclin D3/CCND3 antibody. Validated in WB, ICC/IF and tested in Human. Immunogen corresponding to recombinant ... Anti-Cyclin D3/CCND3 antibody. See all Cyclin D3/CCND3 primary antibodies. ... Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 ... Belongs to the cyclin family. Cyclin D subfamily.. Contains 1 cyclin N-terminal domain. ...
Bob Weinbergs lab contains the insert cyclin D3 and is published in Cell. 1992 Sep 18. 70(6):993-1006. This plasmid is ... Rc/CMV cyclin D3 was a gift from Bob Weinberg (Addgene plasmid # 10912 ; http://n2t.net/addgene:10912 ; RRID:Addgene_10912) ... Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. Hinds PW, Mittnacht S, Dulic V, Arnold A ... Plasmid Rc/CMV cyclin D3 from Dr. ...
Rabbit polyclonal Cyclin D3 (phospho T283) antibody validated for WB and tested in Human, Mouse and Rat. Immunogen ... Anti-Cyclin D3 (phospho T283) antibody. See all Cyclin D3 primary antibodies. ... Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 ... Belongs to the cyclin family. Cyclin D subfamily.. Contains 1 cyclin N-terminal domain. ...
Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 ... Regulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) ... The cyclin subunit imparts substrate specificity to the complex. Interacts with ATF5. Interacts with EIF3K. Component of the ... Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, ...
Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 ... Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, ... Regulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) ... IPR013763. Cyclin-like. IPR036915. Cyclin-like_sf. IPR004367. Cyclin_C-dom. IPR015451. Cyclin_D. IPR006671. Cyclin_N. ...
The human cyclin D3 gene has a TATA-less promoter and a single dominant initiation site. The minimal cyclin D3 promoter ... I have been defining the cis-acting elements and trans-acting factors that control transcription of the human cyclin D3 gene in ... Genomic clones for the human cyclin D3 gene, isolated from a human chromosome 6 library, were analysed by restriction ... reporter constructs containing sequential deletions of the cyclin D3 promoter defined positively and negatively regulated ...
Selected quality suppliers for anti-Cyclin D3 antibodies. ... Order monoclonal and polyclonal Cyclin D3 antibodies for many ... Protein level used designations for anti-Cyclin D3 (CCND3) Antibodies cyclin D3 , G1/S-specific cyclin-D3 , D3-type cyclin , G1 ... Top referenced anti-Cyclin D3 Antibodies. Show all anti-Cyclin D3 (CCND3) Antibodies with Pubmed References. * Human Monoclonal ... Browse our anti-Cyclin D3 (CCND3) Antibodies. Full name:. anti-Cyclin D3 Antibodies (CCND3). On www.antibodies-online.com are ...
Compare and order Cyclin D3 ELISA Kits. View citations, images, detection ranges, sensitivity, prices and more. Recommended ... cyclin D3 , G1/S-specific cyclin-D3 , D3-type cyclin , G1/S-specific cyclin D3 ... Cyclin D3 in Cell Division Cycle * Cyclin D3 in Cell Division Cycle ... Cyclin D3 Antigen Profile Antigen Summary The protein encoded by this gene belongs to the highly conserved cyclin family, whose ...
... cyclin D3) for ICC/IF, IHC-P, WB. Anti-Cyclin D3 pAb (GTX101522) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance. ... CCND3 antibody, G1/S-specific cyclin-D3 antibody, G1/S-specific cyclin D3 antibody, D3-type cyclin antibody, cyclin D3 antibody ... Cyclin D3 antibody detects Cyclin D3 protein at cytoplasm and nucleus by immunofluorescent analysis.. Sample: HeLa cells were ... Green: Cyclin D3 protein stained by Cyclin D3 antibody (GTX101522) diluted at 1:200.. Red: phalloidin, a cytoskeleton marker, ...
Galectin-3 and Cyclin D3 Immunohistochemistry and Tumor Dimensions Are Useful in Distinguishing Follicular Oncocytic Carcinomas ... G. Troncone, A. Iaccarino, M. Russo et al., "Accumulation of p27(kip1) is associated with cyclin D3 overexpression in the ... G. Troncone, M. Volante, A. Iaccarino et al., "Cyclin D1 and D3 overexpression predicts malignant behavior in thyroid fine- ... L. A. Erickson, L. Jin, J. R. Goellner et al., "Pathologic features, proliferative activity, and cyclin D1 expression in ...
GFP vector and cyclin D3 (Cyclin D3), or PTEN and cyclin D3 (PTEN + Cyclin D3). Twenty-four h after transduction, the DNA ... If decreased cyclin D3 expression is required for PTEN-induced cell cycle arrest, then enforced expression of cyclin D3 should ... cyclin D3 levels remained unchanged (Fig. 7) ⇓ . Therefore, decreased levels of cyclin D3 were directly associated with cell ... 250 anti-cyclin D1 (Santa Cruz Biotechnology); 1:250 anti-cyclin D2 (Santa Cruz Biotechnology); or 1:250 anti-cyclin D3 (Santa ...
To determine the role of the cyclin D3 3′-UTR on the cyclin D3 mRNA instability induced by the L-Arg deprivation, the cyclin D3 ... A, Similar expression of cyclin D3 in selected clones of EBV cells transfected with cyclin D3 ORF or cyclin D3 cDNA plasmids. B ... Transfection of cells with cyclin D3 open reading frame or cyclin D3 cDNA. Cyclin D3-negative cell line EBV-Em, generated ... This was the result of a decreased cyclin D3 mRNA stability and a diminished cyclin D3 translation. The arrest in cyclin D3 ...
In the present work, we present novel evidence that a second G(1) cyclin, cyclin D3, is also potently activated by E2F1. First ... Second, all of the growth-stimulatory members of the E2F family (E2F1, -2, and -3A) potently activate a cyclin D3 promoter ... Furthermore, trans-activation of cyclin D3 by ER-E2F1 occurs even in the presence of the protein synthesis inhibitor ... Finally, mapping experiments localize the essential E2F regulatory element of the cyclin D3 promoter to a noncanonical E2F site ...
Inhibition of human CDK4/cyclin D3 expressed in Escherichia coli using retinoblastoma (386 to 928 residues) as substrate after ...
Fig. 8. The parameters of proliferation in control and differentiating A.1 and 1.3 EC cells. EC cells of both lines seeded in the same densities (2.5 x 103 cells/cm2) were cultured with and without 10-6 M RA for 24, 48, 72, and 96 h, respectively. A, growth rates. Cells were lysed in SDS-containing buffer, and the total amounts of protein were used as a measure of cell quantities. Micrograms of total protein are shown on the Y axis. Data are presented as the means of three independent experiments; bars, SE. B, the distribution of cells in cell cycle phases. Cells were fixed in Vindelov s solution, stained with propidium iodide, and analyzed using FACSCalibur equipped with ModFit 2.0 software. The percentages of cells in G1, S, and G2 phases are expressed as the means of three independent experiments; bars, SE.. ...
Early Cycling-independent Changes to p27, Cyclin D2, and Cyclin D3 in Differentiating Mouse Embryonal Carcinoma Cells1 Helena ... cyclin D3 became up-regulated and vice versa. Supposedly, titration of p27 by D-type cyclins, which prevents its inhibitory ... variances in the levels of p27 were strictly followed by variances in the levels of cyclins D2 and D3. In EC cells genetically ... Here, embryonal carcinoma (EC) cell lines were found that differ in their basal levels of p27 inhibitor of cyclin-dependent ...
D3, estrogen receptor-alpha (ERalpha) and progesterone receptor (PR). However, cyclin D3 expression, unlike D1, was confined ... The expression of cyclins D1 and D3 was examined during estradiol-17beta (E(2))-induced mammary tumorigenesis in female August ... Western blot analysis of the E(2)-induced MGTs revealed a marked rise in cyclins D1 (24-fold), D3 (9-fold) and cdk4 (3-fold) ... The kinase activity for cyclins D1 and D3, using retinoblastoma (Rb) as a substrate, in E(2)-induced MGTs and their binding to ...
anti-Cyclin D3, pAb is a polyclonal antibody that crossreacts with human, mouse protein. Works in WB, IP. Important for ... Cyclin D3, ~34kDa, is a member of cyclin D family that promotes cell cycle progression to the DNA systhesis (S) phase. Cyclins ... Cyclin D3 regulates cell proliferation during hematopoiesis, carcinogenesis, and may have function in the terminally ... In recent studies, there is reports that cyclin D3 involves in multiple myeloma and malignant precursor T cells. Essential for ...
Through detecting Cyclin D3 expression in 243 breast cancer patients tissue array, we found Cyclin D3 expression was ... was significantly poor in high Cyclin D3 expression BC patients (p = 0.004). Furthermore, expression of Cyclin D3 was ... is a regulator of Cyclin-dependent kinases 4 and 6. Previous studies revealed that abnormal expression of Cyclin D3 was found ... qRT-PCR was used to detect the mRNA level of Cyclin D3 in BC tissues and BC cell lines. Transwell assay was used to examine the ...
... cyclinD3, Active Human Recombinant Protein \ 40096 for more molecular products just contact us ... Ccnd3 Cyl-3] G1/S-specific cyclin-D3. [CCND3] G1/S-specific cyclin-D3. [Cdk7 Cak Cdkn7 Crk4 Mo15 Mpk-7] Cyclin-dependent kinase ... Cdkn2a P16ink4a] Cyclin-dependent kinase inhibitor 2A (Cyclin-dependent kinase 4 inhibitor A) (CDK4I) (p16-INK4a) (p16-INK4). [ ... Cdkn2a P16ink4a] Cyclin-dependent kinase inhibitor 2A (Cyclin-dependent kinase 4 inhibitor A) (CDK4I) (p16-INK4a) (p16) (p16- ...
Cyclic AMP-dependent phosphorylation of cyclin D3-bound CDK4 determines the passage through the cell cycle restriction point in ... Cyclic AMP-dependent phosphorylation of cyclin D3-bound CDK4 determines the passage through the cell cycle restriction point in ... Immobilised cyclin-dependent kinase 4 fusion proteins and uses thereof par Raspé, Eric , Roger, Pierre P. , Coulonval, Katia , ...
... while the corresponding portion of pRb interacted with either cyclin D3 or cyclin D1. In T98G cells, endogenous cyclin D3- ... while the corresponding portion of pRb interacted with either cyclin D3 or cyclin D1. In T98G cells, endogenous cyclin D3- ... while the corresponding portion of pRb interacted with either cyclin D3 or cyclin D1. In T98G cells, endogenous cyclin D3- ... while the corresponding portion of pRb interacted with either cyclin D3 or cyclin D1. In T98G cells, endogenous cyclin D3- ...
Lack Of Cyclin D3 Induces Skeletal Muscle Fiber Type Shifting, with description: Lack of cyclin d3 induces skeletal muscle ... Lack Of Cyclin D3 Induces Skeletal Muscle Fiber Type Shifting. Feb 5th ...
MAbs specific for cyclin D3, mouse cyclin D1, and PCNA, respectively; clone IF5D =-=(98)-=-, a MAb specific for myogenin; clone ... Critical role played by cyclin D3 in the MyoDmediated arrest of cell cycle during myoblast differentiation by Carlo Cenciarelli ...
  • Erlotinib, at clinically achievable dosages, repressed BEAS-2B cell growth, triggered G 1 arrest, and preferentially reduced cyclin D1 protein expression and transcriptional activation. (aacrjournals.org)
  • During these rounds of replication, cytokinesis is neglected because of the down-regulated expression of AIM-1, and DNA replication occurs through the increased expression of D-type cyclins.As for transcriptional regulation during megakary-opoiesis, GATA-1 plays a central role in the lineage commitment of hematopoietic stem cells toward erythroid/megakaryocytic lineage and subsequent maturation. (springer.com)
  • Recent studies have proposed a number of possible interactions, including USP7 (a ubiquitin-specific protease) ( 11 ), cyclin D3 ( 25 ), elongation factor EF-1δ ( 23 ), the transcription factor BMAL1 ( 24 ), and the major HSV-1 transcriptional regulator ICP4 ( 42 ). (asm.org)
  • The RBP HuR binds to the cyclin D3 mRNA in vitro and endogenously in activated T cells cultured with L-Arg, but not in L-Arg-deprived T cells. (jimmunol.org)
  • By definition, a CDK binds a regulatory protein called a cyclin. (wikipedia.org)
  • There is considerable specificity in which cyclin binds with CDK. (wikipedia.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)
  • 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)
  • Zhuang, SH & Burnstein, KL 1998, ' Antiproliferative effect of 1α,25-dihydroxyvitamin D 3 in human prostate cancer cell line LNCaP involves reduction of cyclin-dependent kinase 2 activity and persistent G1 accumulation ', Endocrinology , vol. 139, no. 3, pp. 1197-1207. (elsevier.com)
  • Therefore, polyploidization of megakaryocytes has been postulated to be caused by either reduction of cyclin B and/or Cdc2 or diminished kinase activity of the complex. (rupress.org)
  • Although PTEN signaling directly regulates p27 KIP1 levels in some settings, in endometrial carcinoma cells, PTEN expression indirectly regulated p27 KIP1 activity by modulating levels of cyclin D3. (aacrjournals.org)
  • We sought to determine the mechanisms leading to a decreased cyclin D3 mRNA stability in activated T cells cultured in medium deprived of L-Arg. (jimmunol.org)
  • RNA-binding protein HuR was found to be increased in T cells cultured in medium with L-Arg and bound to the 3′-untranslated region of cyclin D3 mRNA in vitro and endogenously in activated T cells. (jimmunol.org)
  • The G 0 -G 1 arrest in the cell cycle observed in T cells cultured in L-Arg-deprived medium correlated with an inability to upregulate the expression of cyclin D3 ( 8 ). (jimmunol.org)
  • Early Cycling-independent Changes to p27, Cyclin D2, and Cyclin D3 in Differentiating Mouse Embryonal Carcinoma Cells -- Preclíková et al. (aacrjournals.org)
  • Cyclin D3 regulates cell proliferation during hematopoiesis, carcinogenesis, and may have function in the terminally differentiated cells. (adipogen.com)
  • In recent studies, there is reports that cyclin D3 involves in multiple myeloma and malignant precursor T cells. (adipogen.com)
  • Transwell assay was used to examine the role of Cyclin D3 in the migration and invasion of BC cells. (biomedcentral.com)
  • Further investigation showed Cyclin D3 was involved in the metastasis of BC cells and physically interacted with actin in vivo and in vitro. (biomedcentral.com)
  • Cyclin D3 was widely expressed in many tumor cells. (biomedcentral.com)
  • In T98G cells, endogenous cyclin D3-associated kinase activity showed a clear predisposition to phosphorylate preferentially the C-terminal domain of pRb2/p130, rather than that of pRb. (elsevier.com)
  • D-type cyclins (cyclins D1, D2, and D3) are key components of cell cycle machinery in mammalian cells. (pnas.org)
  • In contrast to rodent β-cells, they contain little or no detectable cyclin D2. (diabetesjournals.org)
  • The current study sought to determine whether the EGFR TKI erlotinib repressed cyclin D1 protein expression in immortalized HBE cells, lung cancer cell lines, and clinical aerodigestive tract cancers. (aacrjournals.org)
  • Similarly, in the developing midbrain-hindbrain region the D-type cyclins were expressed in different subsets of cells. (scielo.br)
  • In mammalian cells, CDK1, with its partners cyclin A2 and B1, alone can drive the cell cycle. (wikipedia.org)
  • In mammalian cells, the activating phosphorylation occurs after cyclin binding. (wikipedia.org)
  • In yeast cells, it occurs before cyclin binding. (wikipedia.org)
  • The bottom left panel shows induction of pRb phosphorylation in INS1 cells that have been transduced with the combination of the adenoviruses Ad.cdk4 plus Ad.cyclin D1. (diabetesjournals.org)
  • G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). (embl.de)
  • Blocking cyclin D1 in the mice drove the breast cancer cells into a kind of permanent retirement called senescence, an irreversible halt to their growth cycle. (medindia.net)
  • Inhibiting cyclin D3 in the T-ALL leukemia mice caused the cancer cells to self-destruct -- a programmed death process called apoptosis. (medindia.net)
  • The D-cyclins determine when a cell begins making DNA in preparation for dividing to form new cells. (medindia.net)
  • In many types of cancer, an excess of cyclins allows cells to grow too fast and form tumors. (medindia.net)
  • Also unknown was whether normal cells could get along without cyclin D1: If not, treating cancer by targeting the protein might be too dangerous. (medindia.net)
  • The authors say the results show that blocking cyclin D "represents a highly selective anticancer strategy that specifically targets cancer cells without significantly affecting normal tissues. (medindia.net)
  • In uninfected cells the G 2 /M transition is regulated by cyclin kinase complex containing cdc2 and, initially, cyclin A, followed by cyclin B. cdc2 is downregulated through phosphorylation by wee-1 and myt-1 and upregulated by cdc-25C phosphatase. (asm.org)
  • Thus, substitution of aspartic acid 199 with alanine in ICP0 abolished stabilization of cyclin D3, reduced the yields of virus from resting cells, and reduced the capacity of the virus to invade the mouse central nervous system from a peripheral site. (asm.org)
  • Subsequently, cyclin E fully phosphorylates Rb and completes its inactivation. (academic.ru)
  • Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (abcam.com)
  • In the present work we set out to examine the significance of cyclin D1-p27 Kip1 interaction in driving cell proliferation within the context of a living animal. (pnas.org)
  • We reasoned that analyses of these cyclin D1 −/− p27 −/− animals would provide a stringent test for the significance of cyclin D1-p27 Kip1 interaction in controlling the cell proliferation of various cyclin D1-dependent lineages. (pnas.org)
  • The BEAS-2B immortalized HBE cell line was exposed to varying concentrations of erlotinib, and effects on proliferation, cell cycle distribution, G 1 cyclin expression, and cyclin D1 reporter activity were measured. (aacrjournals.org)
  • Non-small-cell lung cancer cell lines were also evaluated for changes in proliferation and cyclin protein expression after erlotinib treatments. (aacrjournals.org)
  • Erlotinib also preferentially repressed proliferation and cyclin D1 protein expression in responsive, but not resistant, non-small-cell lung cancer cell lines. (aacrjournals.org)
  • In these cases, marked repression of cyclin D1 and the proliferation marker Ki-67 was detected by immunohistochemical assays. (aacrjournals.org)
  • Our results argue in favor of different functions for D-type cyclins during proliferation and differentiation of neural progenitors. (scielo.br)
  • Cyclin D3 was moderately up-regulated during the proliferation phase, and both cyclin E and D3 were rapidly down-regulated during terminal differentiation. (bloodjournal.org)
  • This sustained ERK activation appears to regulate astrocytic cyclin D1 levels and astrocyte proliferation in vitro and in vivo . (jneurosci.org)
  • Cyclin B1 and B2 can localize Cdk1 to the nucleus and the Golgi, respectively, through a localization sequence outside the CDK-binding region. (wikipedia.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)
  • Silencing of HuR expression significantly impaired cyclin D3 mRNA stability. (jimmunol.org)
  • This was the result of a decreased cyclin D3 mRNA stability and a diminished cyclin D3 translation. (jimmunol.org)
  • However, the mechanisms to explain the decrease in cyclin D3 mRNA stability induced by L-Arg starvation are still unknown. (jimmunol.org)
  • Results shown in this study demonstrate that the decrease in cyclin D3 mRNA stability induced by L-Arg deprivation is dependent on elements within the 3′-UTR of the cyclin D3 mRNA. (jimmunol.org)
  • qRT-PCR was used to detect the mRNA level of Cyclin D3 in BC tissues and BC cell lines. (biomedcentral.com)
  • In addition, D-cyclins play a kinase-independent role by sequestering cell cycle inhibitors p27 Kip1 and p21 Cip1 . (pnas.org)
  • To test the significance of cyclin D1-p27 Kip1 interaction within a living mouse, we crossed cyclin D1-deficient mice with mice lacking p27 Kip1 , and we generated double-mutant cyclin D1 −/− p27 −/− animals. (pnas.org)
  • Here we report that ablation of p27 Kip1 restores essentially normal development in cyclin D1-deficient mice. (pnas.org)
  • Our results provide genetic evidence that p27 Kip1 functions downstream of cyclin D1. (pnas.org)
  • We crossed cyclin D1-deficient mice with mice lacking p27 Kip1 ( 9 - 11 ) and generated double-mutant animals. (pnas.org)
  • The minimal cyclin D3 promoter sequence was identified as a region 173bp upstream of the transcription initiation site. (bl.uk)
  • Transient transfections using CAT (chloramphenicol acetyltransferase) reporter constructs containing sequential deletions of the cyclin D3 promoter defined positively and negatively regulated regions. (bl.uk)
  • Regulation of the cyclin D3 promoter by E2F1. (semanticscholar.org)
  • The synthesis of cyclin D is initiated during G1 and drives the G1/S phase transition. (academic.ru)
  • Previous studies revealed that abnormal expression of Cyclin D3 was found in many different cancers. (biomedcentral.com)
  • Taken together, these in vitro and in vivo findings provide direct evidence for repression of cyclin D1 protein as a surrogate marker of response in aerodigestive tract cancers to erlotinib treatment. (aacrjournals.org)
  • Cyclin D1 which functions as a mitogenic sensor and allosteric activator of CDK4/6, is one of the more frequently altered cell cycle regulators in cancers. (pubmedcentralcanada.ca)
  • Abnormal cyclins D1, D2 and D3 are found in breast, lung, endometrial, pancreatic, and testicular cancers and in multiple myeloma and other blood cancers. (medindia.net)
  • In a key report in Nature in 2001, Sicinski showed that mice engineered to lack cyclin D1 were resistant to developing breast cancer. (medindia.net)
  • Inhibition of cysteine proteinases and proteosome by Ras, Ran and cyclin. (nii.ac.jp)
  • Co-Immunoprecipitation assay and GST-Pull Down assay were used to validate the interaction of Cyclin D3 and its interaction protein. (biomedcentral.com)
  • In most species, there are multiple forms of G1 and G2 cyclins. (embl.de)