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.

Detection of Kaposi's sarcoma herpesvirus DNA sequences in multiple myeloma bone marrow stromal cells. (1/457)

Whether Kaposi's sarcoma herpesvirus (KSHV) is associated with multiple myeloma (MM) remains controversial. We assayed for KSHV DNA sequences in long-term bone marrow stromal cells (BMSCs) from 26 patients with MM and 4 normal donors. Polymerase chain reaction (PCR) using primers which amplify a KSHV gene sequence to yield a 233-bp fragment (KS330233 within open reading frame 26) was negative in all cases. Aliquots of these PCR products were used as templates in subsequent nested PCR, with primers that amplify a 186-bp product internal to KS330233. BMSCs from 24 of 26 (92%) patients with MM and 1 of 4 normal donors were KSHV PCR+. DNA sequence analyses showed interpatient specific mutations (2 to 3 bp). Both Southern blot and sequence analyses confirmed the specificity of PCR results. The presence of the KSHV gene sequences was further confirmed by amplifying T 1.1 (open reading frame [ORF] K7) and viral cyclin D (ORF 72), two other domains within the KSHV genome. Immunohistochemical studies of KSHV PCR+ MM BMSCs demonstrate expression of dendritic cell (DC) lineage markers (CD68, CD83, and fascin). Serological studies for the presence of KSHV lytic or latent antibodies were performed using sera from 53 MM patients, 12 normal donors, and 5 human immunodeficiency virus (HIV)/KSHV+ patients. No lytic or latent antibodies were present in sera from either MM patients or normal donors. Taken together, these findings show that KSHV DNA sequences are detectable in BMSCs from the majority of MM patients, but that serologic responses to KSHV are not present. Ongoing studies are defining whether the lack of antibody response is caused by the absence of ongoing infection, the presence of a novel viral strain associated with MM, or underlying immunodeficiency in these patients.  (+info)

TAFII250, Egr-1, and D-type cyclin expression in mice and neonatal rat cardiomyocytes treated with doxorubicin. (2/457)

Differential display identified that gene fragment HA220 homologous to the transcriptional activator factor II 250 (TAFII250) gene, or CCG1, was increased in hypertrophied rodent heart. To determine whether TAFII250 gene expression is modified after cardiac damage, we measured TAFII250 expression in vivo in mouse hearts after injection of the cardiotoxic agent doxorubicin (DXR) and in vitro in DXR-treated isolated rat neonatal cardiomyocytes. In vivo atrial natriuretic factor (ANF), beta-myosin heavy chain (beta-MHC), Egr-1, and TAFII250 expression increased with dose and time after a single DXR injection, but only ANF and beta-MHC expression were increased after multiple injections. After DXR treatment of neonatal cardiomyocytes we found decreased ANF, alpha-MHC, Egr-1, and TAFII250 expression. Expression of the TAFII250-regulated genes, the D-type cyclins, was increased after a single injection in adult mice and was decreased in DXR-treated cardiomyocytes. Thus expression of Erg-1, TAFII250, and the D-type cyclins is modulated after cardiotoxic damage in adult and neonatal heart.  (+info)

Regulation of Rb and E2F by signal transduction cascades: divergent effects of JNK1 and p38 kinases. (3/457)

The E2F transcription factor plays a major role in cell cycle regulation, differentiation and apoptosis, but it is not clear how it is regulated by non-mitogenic signaling cascades. Here we report that two kinases involved in signal transduction have opposite effects on E2F function: the stress-induced kinase JNK1 inhibits E2F1 activity whereas the related p38 kinase reverses Rb-mediated repression of E2F1. JNK1 phosphorylates E2F1 in vitro, and co-transfection of JNK1 reduces the DNA binding activity of E2F1; treatment of cells with TNFalpha had a similar effect. Fas stimulation of Jurkat cells is known to induce p38 kinase and we find a pronounced increase in Rb phosphorylation within 30 min of Fas stimulation. Phosphorylation of Rb correlated with a dissociation of E2F and increased transcriptional activity. The inactivation of Rb by Fas was blocked by SB203580, a p38-specific inhibitor, as well as a dominant-negative p38 construct; cyclin-dependent kinase (cdk) inhibitors as well as dominant-negative cdks had no effect. These results suggest that Fas-mediated inactivation of Rb is mediated via the p38 kinase, independent of cdks. The Rb/E2F-mediated cell cycle regulatory pathway appears to be a normal target for non-mitogenic signaling cascades and could be involved in mediating the cellular effects of such signals.  (+info)

The p21(Cip1) and p27(Kip1) CDK 'inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts. (4/457)

The widely prevailing view that the cyclin-dependent kinase inhibitors (CKIs) are solely negative regulators of cyclin-dependent kinases (CDKs) is challenged here by observations that normal up-regulation of cyclin D- CDK4 in mitogen-stimulated fibroblasts depends redundantly upon p21(Cip1) and p27(Kip1). Primary mouse embryonic fibroblasts that lack genes encoding both p21 and p27 fail to assemble detectable amounts of cyclin D-CDK complexes, express cyclin D proteins at much reduced levels, and are unable to efficiently direct cyclin D proteins to the cell nucleus. Restoration of CKI function reverses all three defects and thereby restores cyclin D activity to normal physiological levels. In the absence of both CKIs, the severe reduction in cyclin D-dependent kinase activity was well tolerated and had no overt effects on the cell cycle.  (+info)

DNA binding protein dbpA binds Cdk5 and inhibits its activity. (5/457)

Progress in the cell cycle is governed by the activity of cyclin dependent kinases (Cdks). Unlike other Cdks, the Cdk5 catalytic subunit is found mostly in differentiated neurons. Interestingly, the only known protein that activates Cdk5 (i.e. p35) is expressed solely in the brain. It has been suggested that, besides its requirement in neuronal differentiation, Cdk5 activity is induced during myogenesis. However, it is not clear how this activity is regulated in the pathway that leads proliferative cells to differentiation. In order to find if there exists any Cdk5-interacting protein, the yeast two-hybrid system was used to screen a HeLa cDNA library. We have determined that a C-terminal 172 amino acid domain of the DNA binding protein, dbpA, binds to Cdk5. Biochemical analyses reveal that this fragment (dbpA(Cdelta)) strongly inhibits p35-activated Cdk5 kinase. The protein also interacts with Cdk4 and inhibits the Cdk4/cyclin D1 enzyme. Surprisingly, dbpA(Cdelta) does not bind Cdk2 in the two-hybrid assay nor does it inhibit Cdk2 activated by cyclin A. It could be that dbpA's ability to inhibit Cdk5 and Cdk4 reflects an apparent cross-talk between distinct signal transduction pathways controlled by dbpA on the one hand and Cdk5 or Cdk4 on the other.  (+info)

A cyclin D-Cdk4 activity required for G2 phase cell cycle progression is inhibited in ultraviolet radiation-induced G2 phase delay. (6/457)

Cyclin D-Cdk4 complexes have a demonstrated role in G1 phase, regulating the function of the retinoblastoma susceptibility gene product (Rb). Previously, we have shown that following treatment with low doses of UV radiation, cell lines that express wild-type p16 and Cdk4 responded with a G2 phase cell cycle delay. The UV-responsive lines contained elevated levels of p16 post-treatment, and the accumulation of p16 correlated with the G2 delay. Here we report that in UV-irradiated HeLa and A2058 cells, p16 bound Cdk4 and Cdk6 complexes with increased avidity and inhibited a cyclin D3-Cdk4 complex normally activated in late S/early G2 phase. Activation of this complex was correlated with the caffeine-induced release from the UV-induced G2 delay and a decrease in the level of p16 bound to Cdk4. Finally, overexpression of a dominant-negative mutant of Cdk4 blocked cells in G2 phase. These data indicate that the cyclin D3-Cdk4 activity is necessary for cell cycle progression through G2 phase into mitosis and that the increased binding of p16 blocks this activity and G2 phase progression after UV exposure.  (+info)

Transduced p16INK4a peptides inhibit hypophosphorylation of the retinoblastoma protein and cell cycle progression prior to activation of Cdk2 complexes in late G1. (7/457)

Progression of cells through the G1 phase of the cell cycle requires cyclin D:Cdk4/6 and cyclin E:Cdk2 complexes; however, the duration and ordering of these complexes remain unclear. To address this, we synthesized a peptidyl mimetic of the Cdk4/6 inhibitor, p16INK4a that contained an NH2-terminal TAT protein transduction domain. Transduction of TAT-p16 wild-type peptides into cells resulted in the loss of active, hypophosphorylated pRb and elicited an early G1 cell cycle arrest, provided cyclin E:Cdk2 complexes were inactive. We conclude that cyclin D:Cdk4/6 activity is required for early G1 phase cell cycle progression up to, but not beyond, activation of cyclin E:Cdk2 complexes at the restriction point and is thus nonredundant with cyclin E:Cdk2 in late G1.  (+info)

c-Myc regulates cyclin D-Cdk4 and -Cdk6 activity but affects cell cycle progression at multiple independent points. (8/457)

c-myc is a cellular proto-oncogene associated with a variety of human cancers and is strongly implicated in the control of cellular proliferation, programmed cell death, and differentiation. We have previously reported the first isolation of a c-myc-null cell line. Loss of c-Myc causes a profound growth defect manifested by the lengthening of both the G1 and G2 phases of the cell cycle. To gain a clearer understanding of the role of c-Myc in cellular proliferation, we have performed a comprehensive analysis of the components that regulate cell cycle progression. The largest defect observed in c-myc-/- cells is a 12-fold reduction in the activity of cyclin D1-Cdk4 and -Cdk6 complexes during the G0-to-S transition. Downstream events, such as activation of cyclin E-Cdk2 and cyclin A-Cdk2 complexes, are delayed and reduced in magnitude. However, it is clear that c-Myc affects the cell cycle at multiple independent points, because restoration of the Cdk4 and -6 defect does not significantly increase growth rate. In exponentially cycling cells the absence of c-Myc reduces coordinately the activities of all cyclin-cyclin-dependent kinase complexes. An analysis of cyclin-dependent kinase complex regulators revealed increased expression of p27(KIP1) and decreased expression of Cdk7 in c-myc-/- cells. We propose that c-Myc functions as a crucial link in the coordinate adjustment of growth rate to environmental conditions.  (+info)

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...
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 ...
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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 ...
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 ...
Serrano, M., Hannon, G. J., Beach, D. (1993) A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature, 366 (6456). pp. 704-707. ISSN 00280836 (ISSN) Sordella, R., Classon, M., Hu, K. Q., Matheson, S. F., Brouns, M. R., Fine, B., Zhang, L., Takami, H., Yamada, Y., Settleman, J. (2002) Modulation of CREB activity by the Rho GTPase regulates cell and organism size during mouse embryonic development. Developmental Cell, 2 (5). pp. 553-65. ISSN 1534-5807 Sordella, R., Jiang, W., Chen, G. C., Curto, M., Settleman, J. (2003) Modulation of Rho GTPase signaling regulates a switch between adipogenesis and myogenesis. Cell, 113 (2). pp. 147-58. ISSN 0092-8674 (Print) Spector, M. S., Desnoyers, S., Hoeppner, D. J., Hengartner, M. O. (1997) Interaction between the C. elegans cell-death regulators CED-9 and CED-4. Nature, 385 (6617). pp. 653-6. ISSN 0028-0836 (Print) Stasiv, Y., Regulski, M., Kuzin, B., Tully, T., Enikolopov, G. (2001) The Drosophila nitric-oxide ...
Myocarditis is a cardiac disease associated with inflammation and injury of the myocardium. It results from various etiologies, both noninfectious and infectious, but coxsackievirus B3 (CVB3) is still considered the dominant etiological agent. Myocarditis may be caused by direct cytopathic effects of virus, a pathologic immune response to persistent virus, or autoimmunity triggered by the viral infection. The virus enters the myocyte through internalization of the coxsackie-adenoviral receptor (CAR) and its coreceptor, decay-accelerating factor (DAF). Viral proteases cleave various proteins in the host cell. One example is viral protease 2A, which cleaves eukaryote initiation factor 4G (eIF4G) and the dystrophin protein, resulting in a complete shutdown of cap-dependent RNA translation and cytoskeletal destruction in infected cardiomyocytes, respectively. CVB3 also cleaves the member of the Bcl-2 family Bid, leading to apoptosis. CVB3 infection also induces the cleavage of cyclin D protein ...
Teen suicide is when a child ends his or her own life. If you think your child is at risk, talk to your doctor. Learn more about the warning signs here.
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 ...
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 ...
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
View mouse Ccndbp1 Chr2:121008403-121016904 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
Cyclin/cyclin-dependent kinase (CDK) complexes are critical regulators of cellular proliferation. A complex network of regulatory mechanisms has evolved to control their activity, including activating and inactivating phosphorylation of the catalytic CDK subunit and inhibition through specific regulatory proteins. Primate herpesviruses, including the oncogenic Kaposi sarcoma herpesvirus, encode cyclin D homologues. Viral cyclins have diverged from their cellular progenitor in that they elicit holoenzyme activity independent of activating phosphorylation by the CDK-activating kinase and resistant to inhibition by CDK inhibitors. Using sequence comparison and site-directed mutagenesis, we performed molecular analysis of the cellular cyclin D and the Kaposi sarcoma herpesvirus-cyclin to delineate the molecular mechanisms behind their different behavior. This provides evidence that a surface recognized for its involvement in the docking of CIP/KIP inhibitors is required and sufficient to modulate ...
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.
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 ...
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- ...
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 ...
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
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
Cyclin D-Cdk4 complexes have a demonstrated role in G1 phase, regulating the function of the retinoblastoma susceptibility gene product (Rb). Previously, we have shown that following treatment with low doses of UV radiation, cell lines that express wild-type p16 and Cdk4 responded with a G2 phase cell cycle delay. The UV-responsive lines contained elevated levels of p16 post-treatment, and the accumulation of p16 correlated with the G2 delay. Here we report that in UV-irradiated HeLa and A2058 cells, p16 bound Cdk4 and Cdk6 complexes with increased avidity and inhibited a cyclin D3-Cdk4 complex normally activated in late S/early G2 phase. Activation of this complex was correlated with the caffeine-induced release from the UV-induced G2 delay and a decrease in the level of p16 bound to Cdk4. Finally, overexpression of a dominant-negative mutant of Cdk4 blocked cells in G2 phase. These data indicate that the cyclin D3-Cdk4 activity is necessary for cell cycle progression through G2 phase into mitosis 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 ...
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 ...
DROSOPHILA (ZOOLOGIE); HOMÖOSTASE + OSMOREGULATION + REGULATION DES ELEKTROLYTGLEICHGEWICHTES (BIOLOGIE); ZELLWECHSELWIRKUNGEN (CYTOLOGIE); VERDAUUNG (TIERPHYSIOLOGIE); GENMUTATIONEN + PUNKTMUTATIONEN (GENETIK); ZYKLINE (PROTEINE UND PEPTIDE); DROSOPHILA (ZOOLOGY); HOMEOSTASIS + OSMOREGULATION + ELECTROLYTE BALANCE CONTROL (BIOLOGY); CELL INTERACTIONS (CYTOLOGY); DIGESTION (ANIMAL PHYSIOLOGY); GENE MUTATIONS + POINT MUTATIONS (GENETICS); CYCLINS (PROTEINS AND PEPTIDES ...
...(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
The NF-κB transcription factor is one of the most important regulators of the cellular life/death balance and its aberrant activation is associated with cancer ( 4). Therefore, identifying mechanisms for switching off aberrant NF-κB activity could have a major therapeutic benefit. Here, we reveal a novel pathway for down-regulating NF-κB transcriptional activity and inducing apoptosis of colon cancer cells that involves activation of the p38 pathway, inhibition of the cyclin D1/CDK4 kinase complex, and consequent nucleolar targeting of RelA. These findings contribute to our knowledge of the complexities of NF-κB signaling. Furthermore, these findings have considerable relevance to understanding the mechanisms of chemoprevention and cancer therapeutics.. The data presented here provide evidence that p38-mediated inhibition of cyclin D1/CDK4 stimulates the NF-κB pathway to induce nucleolar sequestration of RelA. This conclusion is based on the following findings. First, p38 was rapidly ...
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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 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 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. ...
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 ...
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 ...
Using gene expression analyses, overexpression of the cyclin D genes seems to be one possible unifying event that is seen in almost all multiple myeloma cases with or without an immunoglobulin translocation as compared with normal plasma cells (30). IgH translocations directly dysregulate cyclin D1 or D3 [t(11;14) and t(6;14), respectively] and the C-MAF or MAFB transcription factors dysregulate cyclin D2 [t(14;16) and t(14;20); ref. 31]. In this study, 12 MGUS samples had a similar pattern of cyclin D dysregulation despite a lower proliferative index, suggesting that cyclin D perturbation may indeed be an early and unifying event in plasma cell dyscrasias.. MicroRNAs (miRNA) are single-stranded RNA molecules that regulate gene expression posttranscriptionally and are being implicated in a large number of cancers (32). A study comparing miRNA profiles of normal plasma cells (PC), MGUS, SMM, and multiple myeloma found overexpression of mir-21, mir-106∼25, and mir181a, and mir-181b in MGUS and ...
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 ...
Cyclin E is an important regulator of cell cycle progression. Various studies examined the relationship between cyclin E overexpression with the clinical outcome in patients with breast cancer but yie
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
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% ...
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 ...
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.
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.
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 ...
cyclin-dependent protein serine/threonine kinase regulator activity. • protein binding. • ATP binding. • cyclin binding. • ... Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 ... 1993). "Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent ... CDK4, CMM3, PSK-J3, cyclin-dependent kinase 4, cyclin dependent kinase 4. ...
Cyclin-dependent kinase 5[edit]. Cyclin-dependent kinase 5 (CDK5) is a kinase that has been previously hypothesized to ...
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- ... CDKN1A, CAP20, CDKN1, CIP1, MDA-6, P21, SDI1, WAF1, p21CIP1, cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase ... "Entrez Gene: CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1)".. *^ Gartel AL, Radhakrishnan SK (May 2005). "Lost in ...
ORF72 - vCyclin ORF73 - LANA, latency-associated nuclear antigen- tethers genome to chromosome during latency, also regulates ... cyclin-D, a G protein-coupled receptor, interferon regulatory factor and Flice inhibitory protein (FLIP), as well as DNA ...
Also involved in the phosphorylation and regulation of the RPB1 CTD is cyclin T1 (CCNT1).[19] Cyclin T1 tightly associates and ... "CCNT1 cyclin T1 [ Homo sapiens ]".. Missing or empty ,url=. (help). *^ Cho H, Kim TK, Mancebo H, Lane WS, Flores O, Reinberg D ... "CDK8 cyclin-dependent kinase 8 [Homo sapiens]".. *^ "CTDP1 CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) ... CDK8 and cyclin C (CCNC) are components of the RNA polymerase II holoenzyme that phosphorylate the carboxy-terminal domain (CTD ...
cyclin-dependent protein kinase activating kinase activity. • cyclin binding. • ubiquitin protein ligase binding. • protein ... cyclin-dependent protein kinase holoenzyme complex. • nucleus. • nucleoplasm. • cytosol. • intracellular membrane-bounded ... Cyclin-dependent kinase inhibitor 1A (p21, Cip1). Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human ... regulation of cyclin-dependent protein serine/threonine kinase activity. • G1/S transition of mitotic cell cycle. • G2/M ...
de 2001). «Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at functionally important serine and ... de 2002). «Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4». Mol. Cell ... de 1997). «Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 complexes». Oncogene ( ... cyclins and cyclin dependent kinases». Oncogene (ENGLAND) 15 (2): 143-57. ISSN 0950-9232. PMID 9244350. doi:10.1038/sj.onc. ...
Cyclin dependent kinases (CDKs) are a group of several different kinases involved in regulation of the cell cycle. They ... Lim, S.; Kaldis, P. (16 July 2013). "Cdks, cyclins and CKIs: roles beyond cell cycle regulation". Development. 140 (15): 3079- ... Different combinations of specific CDKs and cyclins mark different parts of the cell cycle. Additionally, the phosphorylation ... Harper, J. W.; Adams, P. D. (August 2001). "Cyclin-Dependent Kinases". Chemical Reviews. 101 (8): 2511-2526. doi:10.1021/ ...
Members of this protein family contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein ... Cyclin M2 is a protein in humans that is encoded by the CNNM2 gene. This gene encodes a member of the ancient conserved domain ... provided by RefSeq, Dec 2011]. "Entrez Gene: Cyclin M2". Retrieved 2013-02-23. ...
Cyclins are proteins that play a key role in regulating the cell-division cycle. Hunt found that cyclins begin to be ... He and others subsequently showed that cyclins bind and activate a family of protein kinases, now called the cyclin-dependent ... the protein cyclin which is a component of cyclin dependent kinases, demonstrating his ability to grasp the significance of the ... He showed that cyclins are degraded periodically at each cell division, a mechanism proved to be of general importance for cell ...
The mitotic cyclins can be grouped as cyclins A & B. These cyclins have a nine residue sequence in the N-terminal region called ... Cyclin, a regulatory subunit. The cyclins are necessary for the kinase subunit to function with the appropriate substrate. ... As the concentration of Cyclin B/CDK1 increases, the heterodimer promotes APC to polyubiquitinate Cyclin B/CDK1. Smith, L. ... Cyclin-dependent kinase 1 (CDK1), the cyclin-dependent kinase subunit. It uses ATP to phosphorylate specific serine and ...
These transitions are controlled by the cyclin-dependent kinase Cdk1.[10] Though the proteins that control Cdk1 are well ... a cyclin-dependent kinase, on a tyrosine residue. Cdc2 drives entry into mitosis by phosphorylating a wide range of targets. ...
Hsi ED, Zukerberg LR, Yang WI, Arnold A (May 1996). "Cyclin D1/PRAD1 expression in parathyroid adenomas: an immunohistochemical ... Parathyroid adenoma can be associated with overexpression of the cyclin D1 gene. Hyperparathyroidism is confirmed by blood ...
Deshaies, R.J., Chau, V., and Kirschner, M.W. (1995). Ubiquitination of the G1 cyclin Cln2p by a Cdc34p-dependent pathway. EMBO ... Verma, R., Annan, R., Huddleston, M., Carr, S., Reynard, G., and Deshaies, R.J. (1997). Phosphorylation of Sic1p by G1 cyclin/ ... they established that an early step in the release of Cdc14 from Net1 is the phosphorylation of Net1 by the mitotic cyclin-Cdk ... Phosphorylation by cyclin B-Cdk underlies release of mitotic exit. Science 305, 516-519 ...
Cyclin-L2 is a protein that in humans is encoded by the CCNL2 gene. The protein encoded by this gene belongs to cyclin family. ... 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 ... CCNL2 cyclin L2". Human CCNL2 genome location and CCNL2 gene details page in the UCSC Genome Browser. Maruyama K, Sugano S ( ...
p16 inhibits cyclin dependent kinases 4 and 6 (CDK4 and CDK6) and thereby activates the retinoblastoma (Rb) family of proteins ... "CDKN2A cyclin dependent kinase inhibitor 2A [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-10-11. ... CDKN2A, also known as cyclin-dependent kinase Inhibitor 2A, is a gene which in humans is located at chromosome 9, band p21.3. ... "CDKN2A - Cyclin-dependent kinase inhibitor 2A - Homo sapiens (Human) - CDKN2A gene & protein". www.uniprot.org. Retrieved 2016- ...
2004). "Characterization of cyclin L2, a novel cyclin with an arginine/serine-rich domain: phosphorylation by DYRK1A and ... "Entrez Gene: CCNL1 cyclin L1". Human CCNL1 genome location and CCNL1 gene details page in the UCSC Genome Browser. Zhang QH, Ye ... Cyclin-L1 is a protein that in humans is encoded by the CCNL1 gene. GRCh38: Ensembl release 89: ENSG00000163660 - Ensembl, May ... 2006). "Cyclin L1 (CCNL1) gene alterations in human head and neck squamous cell carcinoma". Br. J. Cancer. 94 (7): 1041-4. doi: ...
He holds a US and international patent on Activators of Cyclin-Dependent Kinases (ACDK) and has mentored many doctoral scholars ... 19-. ISBN 978-94-007-0265-3. She, Jin-Xiong; Wang, Cong-Yi; Kumar, G. Pradeep (2017-12-20). "Activators of cyclin-dependent ...
cyclin-dependent protein kinase 5 activator activity. • lipid binding. Cellular component. • cytoplasm. • cyclin-dependent ... CDK5R2, NCK5AI, P39, p39nck5ai, cyclin-dependent kinase 5, regulatory subunit 2 (p39), cyclin dependent kinase 5 regulatory ... Cyclin-dependent kinase 5 activator 2 is an enzyme that in humans is encoded by the CDK5R2 gene.[5][6] ... "Entrez Gene: CDK5R2 cyclin-dependent kinase 5, regulatory subunit 2 (p39)".. *^ Dhavan, Rani; Greer Paul L; Morabito Maria A; ...
As their name implies, CDKs are heavily dependent on specific cyclin molecules for activation. Once combined, the CDK-cyclin ... Yee A, Wu L, Liu L, Kobayashi R, Xiong Y, Hall FL (Jan 1996). "Biochemical characterization of the human cyclin-dependent ... A prominent kinase is cyclin-dependent kinase (or CDK), which comprises a sub-family of protein kinases. ...
Mantle cell lymphoma is excluded due to the lack of CD5 and cyclin-D1 expression. Clonal rearrangements of the immunoglobulin ... July 1998). "Absence of cyclin D1 protein expression in splenic marginal zone lymphoma". Mod. Pathol. 11 (7): 601-6. PMID ... November 1999). "Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q ...
... the cyclin-dependent kinases (CDKs), where substrates are recognized by the cyclin subunit, MAPKs associate with their ... The closest relatives of MAPKs are the cyclin-dependent kinases (CDKs).[2] ...
Takahashi-Yanaga F, Sasaguri T (Apr 2008). "GSK-3beta regulates cyclin D1 expression: a new target for chemotherapy". Cellular ...
cyclin-dependent protein kinase inhibitor activity. • protein binding. • transcription factor binding. • protein kinase binding ... negative regulation of cyclin-dependent protein kinase activity. • negative regulation of transcription, DNA-dependent. • ...
... cyclin box.' In mammalian cells, 9 cyclin species have been identified, and they are referred to as cyclins A through I. Cyclin ... Cyclin G-associated kinase received its name because it immunoprecipitated with cyclin G though it now appears to not be ... Cyclin G-associated kinase (GAK) is a serine/threonine kinase that in humans is encoded by the GAK gene. In all eukaryotes, the ... Cyclin G-associated kinase is a two domain cystolic protein. The domain of interest is the C-terminal domain which consists of ...
"Entrez Gene: RUNX1T1 runt-related transcription factor 1; translocated to, 1 (cyclin D-related)". Rual JF, Venkatesan K, Hao T ...
Cyclin E is one of the key regulators of the G(1)/S transition in the cell cycle. Overexpression of cyclin E has been observed ... One hundred and seventy-one patients (63%) had low cyclin E, 72 (27%) medium and 27 (10%) had high cyclin E content. Fifty-six ... of those with low cyclin E content (P , 0.0001). In p53 mutated breast cancers high cyclin E content was associated with ... Overexpression of cyclin E protein is associated with specific mutation types in the p53 gene and poor survival in human breast ...
... consisting of cyclin B1 and the cyclin-dependent kinase Cdc2 was assessed in primary cultures of postmitotic ventricular adult ... Simultaneous ectopic expression of wild-type versions of cyclin B1 and Cdc2 was sufficient to induce MPF activity. ... to divide shortly after birth and an irreversible cell cycle arrest is evident accompanied by the downregulation of cyclin- ...
cyclin E, A (Cdk2,1) cyclin A, B, B3 (Cdk1) H. sapiens cyclin D 1,2,3 (Cdk4, Cdk6) cyclin E (Cdk2) cyclin A (Cdk2, Cdk1) cyclin ... Cyclin A / CDK2 - active in S phase.. *Cyclin D / CDK4, Cyclin D / CDK6, and Cyclin E / CDK2 - regulates transition from G1 to ... cyclin D (Cdk4) cyclin E (Cdk2) cyclin E, A (Cdk2,1) cyclin A, B, B3 (Cdk1) ... G1 cyclins, G1/S cyclins, S cyclins, and M cyclins. This division is useful when talking about most cell cycles, but it is not ...
Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which ... Cyclin-T2 is a protein that in humans is encoded by the CCNT2 gene. The protein encoded by this gene belongs to the highly ... This cyclin and its kinase partner CDK9 were found to be subunits of the transcription elongation factor p-TEFb. The p-TEFb ... "Entrez Gene: CCNT2 cyclin T2". Simone C, Bagella L, Bellan C, Giordano A (Jun 2002). "Physical interaction between pRb and cdk9 ...
Source for information on cyclin: A Dictionary of Biology dictionary. ... cyclin Any of a family of proteins that help control the various phases of the cell cycle. Their concentrations fluctuate in ... cyclin Any of a family of proteins that help control the various phases of the cell cycle. Their concentrations fluctuate in ... cyclin A Dictionary of Biology © A Dictionary of Biology 2004, originally published by Oxford University Press 2004. ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Cyclin-dependent kinases are a type of serine/threonine kinase which are activated by cyclins to drive the progress of the cell ... These genes include cyclin E, which binds to CDK4, driving the cell cycle into the S phase. Cyclin A is also produced, which ... Cyclin-dependent kinases are a type of serine/threonine kinase which are activated by cyclins to drive the progress of the cell ... Cyclin Dependent Kinases in the Cell Cycle. Initially, a mitogenic stimulus leads to the upregulation of cyclin D gene ...
... like other cyclins, maybe) to mimic the characteristics of cyclin E. If you have any ideas, please let me know. Thanks. Mike * ... Cyclin E-Fix. micro-mike micro-mike at cox.net Sun Mar 3 16:33:22 EST 2002 *Previous message: THE SECRET the IRS is TERRIFIED ... But, with Cyclin E antibodies, we get cytoplasmic staining rather than nuclear staining which is mentioned in all the ...
CYCLIN; Cyclin box fold. Protein binding domain functioning in cell-cycle and transcription control. Present in cyclins, TFIIB ... CYCLIN; Cyclin box fold. Protein binding domain functioning in cell-cycle and transcription control. Present in cyclins, TFIIB ... CYCLIN; Cyclin box fold. Protein binding domain functioning in cell-cycle and transcription control. Present in cyclins, TFIIB ... Cyclin I: a new cyclin encoded by a gene isolated from human brain. Nakamura T, et al. Exp Cell Res, 1995 Dec. PMID 7493655 ...
Comparison of the structure of the unbound cyclin with the structure of cyclin A complexed with CDK2 reveals that cyclin A does ... cyclin A-3, corresponding to residues 171-432 of human cyclin A. The cyclin box has an alpha-helical fold comprising five alpha ... Cyclins exhibit diverse sequences but all share homology over a region of approximately 100 amino acids, termed the cyclin box ... The structural results indicate a role for the cyclin-box fold both as a template for the cyclin family and as a generalised ...
... Charles Yang cyang at jhunix.hcf.jhu.edu Fri Oct 6 15:33:24 EST 1995 *Previous message: luciferase ... My problem: I cant find the nucleotide and amino acid sequences for the Cyclin H gene (the human counterpart to CCL1) and its ...
Cyclin-Up Inn 3 br home overlooking Whalan and the Root River Trail, Pet Friendl. The house sleeps 8 in 3 queen sized beds and ... Cyclin-Up Inn 3 br home overlooking Whalan and the Root River Trail, Pet Friendl. The house sleeps 8 in 3 queen sized beds and ... Cyclin-Up Inn 3 br home overlooking Whalan and the Root River Trail, Pet Friendl. The house sleeps 8 in 3 queen sized beds and ... Cyclin-Up Inn 3 br home overlooking Whalan and the Root River Trail, Pet Friendl. The house sleeps 8 in 3 queen sized beds and ...
Activation of cyclin A-dependent protein kinases during apoptosis. W Meikrantz, S Gisselbrecht, S W Tam, and R Schlegel ... These findings suggest that at least one of the biochemical steps required for mitosis, activation of cyclin A-dependent ... Where examined, both Cdc2 and Cdk2, the catalytic subunits known to associate with cyclin A, were activated. Stable ... to 7-fold increases in cyclin A-associated histone H1 kinase activity, levels approximating the mitotic value. ...
Construction of a Cyclin D1-Cdk2 Fusion Protein to Model the Biological Functions of Cyclin D1-Cdk2 Complexes ... Cyclin D1 Promotes Cell Cycle Progression through Enhancing NDR1/2 Kinase Activity Independent of Cyclin-dependent Kinase 4 ... D-Type Cyclins and Their Cyclin-dependent Kinases: G1 Phase Integrators of the Mitogenic Response ... Heat Shock Protein B8, a Cyclin-Dependent Kinase Independent Cyclin D1 Target Gene, Contributes to Its Effects on Radiation ...
... the discovery of cyclin-dependent ki- nases (Cdks) ushered in a new era in the understanding of cell proliferation and its ... the cyclin), led to a simple model for cell cycle control. Modulation of cyclin accumulation, and thereby Cdk activation, was ... CDK CKI Zellzyklus biochemistry biology cancer cell cell cycle cellular differentiation cellular growth cyclin-dependent kinase ... More than 10 years ago, the discovery of cyclin-dependent ki- nases (Cdks) ushered in a new era in the understanding of cell ...
E type cyclins (E1 and E2) are believed to drive cell entry into the S phase. It is widely assumed that the two E type cyclins ... However, endoreplication of trophoblast giant cells and megakaryocytes is severely impaired in the absence of cyclin E. Cyclin ... Cyclin E ablation in the mouse.. Geng Y., Yu Q., Sicinska E., Das M., Schneider J.E., Bhattacharya S., Rideout W.M., Bronson R. ... These findings define a molecular function for E type cyclins in cell cycle reentry and reveal a differential requirement for ...
Although cyclin D1 had no effect on STAT3 DNA binding, cyclin D1 did bind to the transcriptional activation domain of STAT3, ... Bienvenu et al. have found that cyclin D1, independent of cyclin-dependent kinase 4 (Cdk4) activity, can inhibit STAT3-mediated ... Endogenous cyclin D1 associated with STAT3 in cells treated for 2 hours after treatment with interleukin 6 (IL-6), an activator ... F. Bienvenu, H. Gascan, O. Coqueret, Cyclin D1 represses STAT3 activation through a Cdk4-independent mechanism. J. Biol. Chem. ...
Cyclin D1 governs microRNA processing in breast cancer Cyclin D1 controls cell cycle progression and microRNA biogenesis ... Cyclin D1 governs microRNA processing in breast cancer. Thomas Jefferson University. Journal. Nature Communications. Keywords. ... regulates expression of cyclin D1. Furthermore, the group showed that many cancer patients encode a form of cyclin D1 that ... Because the cyclin D1 gene has been implicated in a variety of other human cancers these findings may have broad implications ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
... balczonr at my-dejanews.com balczonr at my-dejanews.com Tue Sep 22 13:25:16 EST 1998 ...
Cyclin-dependent kinase synonyms, Cyclin-dependent kinase pronunciation, Cyclin-dependent kinase translation, English ... dictionary definition of Cyclin-dependent kinase. n. Any of various enzymes that catalyze the transfer of a phosphate group ... Targeting cyclins and cyclin-dependent kinases in cancer: lessons from mice, hopes for therapeutic applications in human.. The ... STRUCTURAL STUDIES OF CYCLIN-DEPENDENT KINASE INHIBITORS: DYNAMICS AND FLEXIBILITY ARE THE STORY.. STRUCTURAL STUDIES OF CYCLIN ...
We have previously demonstrated that loss of one candidate gene at this locus, cyclin-dependent kinase inhibitor 2B (Cdkn2b), ...
... Carmela Rinaldi,1 Natalia Maria Malara,2 Rosalia DAngelo,1 ... Carmela Rinaldi, Natalia Maria Malara, Rosalia DAngelo, et al., "Age Dependent Switching Role of Cyclin D1 in Breast Cancer," ...
The results obtained suggest that the increment of the levels of cyclin D1 in intra-ductal breast tumors in older woman that we ... have examined is significantly associated with a lower proliferation rate.Conclusion: Cyclin D1, which characterizes tumor in ... Cyclin D1 gene (CCND1) plays pivotal roles in the development of several human cancers, including breast cancer, functioning as ... Age Dependent Switching Role of Cyclin D1 in Breast Cancer. Carmela Rinaldi. ,1 Natalia Maria Malara. ,2 Rosalia DAngelo. ,1 ...
Download the full report: https://www.reportbuyer.com/product/5190761 Summary Cyclin Dependent Kinase 9 (Tat Associated Kinase ... This protein forms a complex with and is regulated by its regulatory subunit cyclin T or cyclin K. HIV-1 Tat protein was found ... The latest report Cyclin Dependent Kinase 9 - Pipeline Review, H2 2017, outlays comprehensive information on the Cyclin ... Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase ...
  • To get a better understanding of the cardiac cell cycle and its regulation, the effect of functional recovery of the mitosis-promoting factor (MPF) consisting of cyclin B1 and the cyclin-dependent kinase Cdc2 was assessed in primary cultures of postmitotic ventricular adult rat cardiomyocytes ( ARC). (uni-muenchen.de)
  • 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). (ingentaconnect.com)
  • Our genome-wide analysis identified 52 expressed cyclin genes in tomato. (mdpi.com)
  • Quantitative real-time polymerase chain reaction analysis indicates that the expression patterns of tomato cyclin genes were significantly different in vegetative and reproductive stages. (mdpi.com)
  • Transcription of most cyclin genes can be enhanced or repressed by exogenous application of gibberellin, which implies that gibberellin maybe a direct regulator of cyclin genes. (mdpi.com)
  • Cyclin C was originally identified by a genetic screen for human and Drosophila cDNAs that complement a triple knock-out of the CLN genes in Saccharomyces cerevisiae. (novusbio.com)
  • The treatment of quiescent cells with growth factors results in the transcriptional activation of the D-type cyclin genes during G1. (bl.uk)
  • Comparison of these results with those for the cyclin D1 and D2 genes should elucidate how transcription of these genes is co-ordinately regulated by growth factors. (bl.uk)
  • Background: Cyclin D1 gene (CCND1) plays pivotal roles in the development of several human cancers, including breast cancer, functioning as an oncogene. (hindawi.com)
  • Auf www.antikoerper-online.de finden Sie aktuell 24 Cyclin D1 (CCND1) Proteine von 9 unterschiedlichen Herstellern. (antikoerper-online.de)
  • Cyclin specificity: how many wheels do you need on a unicycle? (biomedsearch.com)
  • We looked for but did not obtain strong evidence for cyclin specificity in the use of different mechanisms to control rereplication: both the S-phase cyclin Clb5 and the mitotic cyclins Clb1-4 were inferred to be capable of imposing ORC-based and MCM-based controls. (genetics.org)
  • Cyclins exhibit diverse sequences but all share homology over a region of approximately 100 amino acids, termed the cyclin box. (nih.gov)
  • Exendin-4 stimulated cyclin A2 promoter activity via the cAMP-cAMP response element binding protein pathway. (diabetesjournals.org)
  • The human cyclin D3 gene has a TATA-less promoter and a single dominant 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)
  • This preferential activity was present in a small, 335-bp cyclin A1 promoter fragment that contained several potential c-myb binding sites. (bloodjournal.org)
  • We have solved the crystal structure, at 2.0 A resolution, of an active recombinant fragment of bovine cyclin A, cyclin A-3, corresponding to residues 171-432 of human cyclin A. The cyclin box has an alpha-helical fold comprising five alpha helices. (nih.gov)
  • Recombinant protein encompassing a sequence within the center region of human Cyclin B1. (genetex.com)
  • Recombinant cyclin/CDK holoenzymes were purified from Sf9 cells engineered to produce baculoviruses that express a specific cyclin or CDK. (aacrjournals.org)
  • Hemodynamic forces modulate EC proliferative phenotype through the miR (show MLXIP ELISA Kits )-23b/ CAK/cyclin H pathway. (antibodies-online.com)
  • This study suggests that TMA technique could be useful to study histological correlations and prognostic significance of cyclin A on breast cancer on a large scale. (kb.se)
  • Here, we demonstrate that E type cyclins are largely dispensable for mouse development. (uniprot.org)
  • CBP-S436A islets exhibited elevated cyclin A2, reduced p27, and no changes in D-type cyclins, PDX-1, or Skp2. (diabetesjournals.org)
  • C-, H- and J18 types only contain a cyclin-C domain, and U-type cyclins contain another potential cyclin domain. (mdpi.com)
  • NMB or NMBR silencing inhibited M-CSF (zeige CSF1R Proteine )/ c-Fms (zeige CSF1R Proteine )-mediated downstream signaling pathways like activation of ERK (zeige EPHB2 Proteine ) and Akt (zeige AKT1 Proteine ) and induction of D-type cyclins, cyclin D1 and D2. (antikoerper-online.de)
  • Furthermore, the group showed that many cancer patients encode a form of cyclin D1 that evades negative feedback from the non coding genome. (eurekalert.org)
  • We also found that cyclin E-deficient cells are relatively resistant to oncogenic transformation. (uniprot.org)
  • This supports results from earlier studies that suggest that cyclin D1 could be used as a prognostic biomarker. (fiercebiotech.com)
  • From the determination of the structure of cyclin A, together with results from biochemical and genetic analyses, we can identify which parts of the cyclin molecular may contribute to cyclin A structure and function. (nih.gov)