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.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 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 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 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 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 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 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.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.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 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 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-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.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.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.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.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.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.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.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.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.Protein Phosphatase 2: A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes.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.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.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.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.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.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.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 Line, Tumor: A cell line derived from cultured tumor cells.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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/)Oncogene Proteins: Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).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.Interleukin-12 Receptor beta 2 Subunit: A subunit of the interleukin-12 receptor. It plays a role in receptor signaling by associating with JANUS KINASE 2.Proto-Oncogene Proteins c-mdm2: An E3 UBIQUITIN LIGASE that interacts with and inhibits TUMOR SUPPRESSOR PROTEIN P53. Its ability to ubiquitinate p53 is regulated by TUMOR SUPPRESSOR PROTEIN P14ARF.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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)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.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.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.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.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.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.Adenocarcinoma, Papillary: An adenocarcinoma containing finger-like processes of vascular connective tissue covered by neoplastic epithelium, projecting into cysts or the cavity of glands or follicles. It occurs most frequently in the ovary and thyroid gland. (Stedman, 25th ed)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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.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.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.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.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.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.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.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.Phosphoprotein Phosphatases: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)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.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.A Kinase Anchor Proteins: A structurally-diverse family of intracellular-signaling adaptor proteins that selectively tether specific protein kinase A subtypes to distinct subcellular sites. They play a role in focusing the PROTEIN KINASE A activity toward relevant substrates. Over fifty members of this family exist, most of which bind specifically to regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASE TYPE II such as CAMP PROTEIN KINASE RIIALPHA or CAMP PROTEIN KINASE RIIBETA.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.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.Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.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.Retroviridae: Family of RNA viruses that infects birds and mammals and encodes the enzyme reverse transcriptase. The family contains seven genera: DELTARETROVIRUS; LENTIVIRUS; RETROVIRUSES TYPE B, MAMMALIAN; ALPHARETROVIRUS; GAMMARETROVIRUS; RETROVIRUSES TYPE D; and SPUMAVIRUS. A key feature of retrovirus biology is the synthesis of a DNA copy of the genome which is integrated into cellular DNA. After integration it is sometimes not expressed but maintained in a latent state (PROVIRUSES).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.

Control of cell cycle progression by c-Jun is p53 dependent. (1/94)

The c-jun proto-oncogene encodes a component of the mitogen-inducible immediate-early transcription factor AP-1 and has been implicated as a positive regulator of cell proliferation and G1-to-S-phase progression. Here we report that fibroblasts derived from c-jun-/- mouse fetuses exhibit a severe proliferation defect and undergo a prolonged crisis before spontaneous immortalization. The cyclin D1- and cyclin E-dependent kinases (CDKs) and transcription factor E2F are poorly activated, resulting in inefficient G1-to-S-phase progression. Furthermore, the absence of c-Jun results in elevated expression of the tumor suppressor gene p53 and its target gene, the CDK inhibitor p21, whereas overexpression of c-Jun represses p53 and p21 expression and accelerates cell proliferation. Surprisingly, protein stabilization, the common mechanism of p53 regulation, is not involved in up-regulation of p53 in c-jun-/- fibroblasts. Rather, c-Jun regulates transcription of p53 negatively by direct binding to a variant AP-1 site in the p53 promoter. Importantly, deletion of p53 abrogates all defects of cells lacking c-Jun in cell cycle progression, proliferation, immortalization, and activation of G1 CDKs and E2F. These results demonstrate that an essential, rate-limiting function of c-Jun in fibroblast proliferation is negative regulation of p53 expression, and establish a mechanistic link between c-Jun-dependent mitogenic signaling and cell-cycle regulation.  (+info)

Altered regulation of cyclin G in human breast cancer and its specific localization at replication foci in response to DNA damage in p53+/+ cells. (2/94)

Cyclin G, a recent addition to the cyclin family, was initially identified in screens for new src kinase family members and soon thereafter by differential screening for transcriptional targets of the tumor suppressor gene, p53. We have identified cyclin G as being overexpressed in breast and prostate cancer cells using differential display polymerase chain reaction screening. We demonstrate here that cyclin G is overexpressed in human breast and prostate cancer cells and in cancer cells in situ from tumor specimens. Cyclin G expression was tightly regulated throughout the cell cycle in normal breast cells, peaking at the S and G2/M phases of the cell cycle with lower levels in G1. The cell cycle-dependent expression was absent in breast cancer cells. Following DNA damage in normal p53+/+ cells, cyclin G is triggered to cluster in discrete nuclear DNA replication foci that contain replication-associated proteins such as proliferating cell nuclear antigen (PCNA). While p53-/- cells displayed a faint cyclin G nuclear staining pattern, there was no increased expression and no change in distribution of the staining pattern after DNA damage. The specific subcellular localization of cyclin G at DNA replication foci provides an additional link between p53-mediated growth arrest and cell cycle regulation and suggests that cyclin G may act as an effector of p53-mediated events by functional association with replication foci protein(s).  (+info)

G1 checkpoint protein and p53 abnormalities occur in most invasive transitional cell carcinomas of the urinary bladder. (3/94)

The G1 cell cycle checkpoint regulates entry into S phase for normal cells. Components of the G1 checkpoint, including retinoblastoma (Rb) protein, cyclin D1 and p16INK4a, are commonly altered in human malignancies, abrogating cell cycle control. Using immunohistochemistry, we examined 79 invasive transitional cell carcinomas of the urinary bladder treated by cystectomy, for loss of Rb or p16INK4a protein and for cyclin D1 overexpression. As p53 is also involved in cell cycle control, its expression was studied as well. Rb protein loss occurred in 23/79 cases (29%); it was inversely correlated with loss of p16INK4a, which occurred in 15/79 cases (19%). One biphenotypic case, with Rb+p16- and Rb-p16+ areas, was identified as well. Cyclin D1 was overexpressed in 21/79 carcinomas (27%), all of which retained Rb protein. Fifty of 79 tumours (63%) showed aberrant accumulation of p53 protein; p53 staining did not correlate with Rb, p16INK4a, or cyclin D1 status. Overall, 70% of bladder carcinomas showed abnormalities in one or more of the intrinsic proteins of the G1 checkpoint (Rb, p16INK4a and cyclin D1). Only 15% of all bladder carcinomas (12/79) showed a normal phenotype for all four proteins. In a multivariate survival analysis, cyclin D1 overexpression was linked to less aggressive disease and relatively favourable outcome. In our series, Rb, p16INK4a and p53 status did not reach statistical significance as prognostic factors. In conclusion, G1 restriction point defects can be identified in the majority of bladder carcinomas. Our findings support the hypothesis that cyclin D1 and p16INK4a can cooperate to dysregulate the cell cycle, but that loss of Rb protein abolishes the G1 checkpoint completely, removing any selective advantage for cells that alter additional cell cycle proteins.  (+info)

Ectopic expression of Cdc25A accelerates the G(1)/S transition and leads to premature activation of cyclin E- and cyclin A-dependent kinases. (4/94)

Human Cdc25 phosphatases play important roles in cell cycle regulation by removing inhibitory phosphates from tyrosine and threonine residues of cyclin-dependent kinases. Three human Cdc25 isoforms, A, B, and C, have been discovered. Cdc25B and Cdc25C play crucial roles at the G(2)/M transition. In the present study, we have investigated the function of human Cdc25A phosphatase. Cell lines that express human Cdc25A in an inducible manner have been generated. Ectopic expression of Cdc25A accelerates the G(1)/S-phase transition, indicating that Cdc25A controls an event(s) that is rate limiting for entry into S phase. Furthermore, we carried out a detailed analysis of the expression and activation of human Cdc25A. Activation of endogenous Cdc25A occurs during late G(1) phase and increases in S and G(2) phases. We further demonstrate that Cdc25A is activated at the same time as cyclin E- and cyclin A-dependent kinases. In vitro, Cdc25A dephosphorylates and activates the cyclin-Cdk complexes that are active during G(1). Overexpression of Cdc25A in the inducible system, however, leads to a premature activation of both cyclin E-Cdk2 and cyclin A-Cdk2 complexes, while no effect of cyclin D-dependent kinases is observed. Furthermore, Cdc25A overexpression induces a tyrosine dephosphorylation of Cdk2. These results suggest that Cdc25A is an important regulator of the G(1)/S-phase transition and that cyclin E- and cyclin A-dependent kinases act as direct targets.  (+info)

A role of cyclin G in the process of apoptosis. (5/94)

Cyclin G was previously identified as a target gene of the p53 tumor suppresser protein, and levels of cyclin G are increased after induction of p53 by DNA damage. However, the function of cyclin G has not been established. To determine the effect of increased expression of cyclin G, retroviruses encoding cyclin G were constructed and used to infect three different murine cell lines. Cyclin G protein levels induced by the retroviruses were within the range seen after DNA damage induction of p53. In each case we observed that such over-expression of cyclin G augments the apoptotic process. TNF-alpha induction of apoptosis is increased by expression of cyclin G in NIH3T3 fibroblasts which express p53, as well as in 10.1 fibroblasts which contain no p53 allele. Additionally, we observed that while cyclin G expression is markedly reduced upon aggregate formation in embryonic carcinoma P19 cells, retrovirus-mediated over-expression of cyclin G enhances apoptotic cell death in aggregated P19 cells, and increases the extent of apoptosis caused by retinoic acid or serum starvation of these cells. These data demonstrate that cyclin G plays a facilitating role in modulating apoptosis induced by different stimuli. Moreover, we have discovered that cyclin G expression is rapidly induced in P19 cells after exposure to Bone Morphogenic Protein-4 (BMP-4), suggesting that cyclin G may mediate apoptotic signals generated by BMP-4.  (+info)

Interferon-alpha inhibits proliferation in human T lymphocytes by abrogation of interleukin 2-induced changes in cell cycle-regulatory proteins. (6/94)

IFN-alpha exerts prominent regulatory functions on the immune system. One such effect is the inhibition of proliferation of in vitro stimulated T lymphocytes. The exact physiological function of this activity is not known, but it has been implicated in the antiviral effects of IFN, its antitumor action in T-cell malignancies, and the regulation of the in vivo T-cell response. Here, we have investigated the mechanism underlying the IFN-alpha-mediated growth inhibition of normal human PHA- and IL-2-stimulated T lymphocytes by an analysis of how IFN-alpha treatment influences known molecular events that normally accompany the transition from quiescence to proliferation in these cells. IFN-alpha treatment was found to profoundly block S-phase entry of stimulated T lymphocytes. This correlated with a strong inhibition of IL-2-induced changes in G1-regulatory proteins, including the prevented up-regulation of G1 cyclins and cyclin-dependent kinases as well as an abrogation of mitogen-induced reduction of p27Kip1 levels. This latter effect was due to a maintained stability of the p27Kip1 protein in the IFN-alpha-treated cells. In line with these findings, phosphorylation of the pocket proteins was abrogated in IFN-alpha-treated cells. Furthermore, our data indicate that IFN-alpha has selective effects on the pathways that emerge from the IL-2 receptor because IFN-alpha treatment does not block IL-2-induced up-regulation of c-myc or Cdc25A.  (+info)

Role of cell cycle regulatory proteins in cerebellar granule neuron apoptosis. (7/94)

Cerebellar granule neurons (CGNs) undergo apoptosis when deprived of depolarizing concentrations of KCl, but the underlying molecular mechanisms are not yet clear. Although caspases have been postulated to be involved in CGN cell death, inhibitors of caspases failed to prevent apoptosis under our culture conditions, suggesting an involvement of other molecules and pathways. We find that inhibitors of cyclin-dependent kinases--flavopiridol, olomoucine, and roscovitine--protect CGNs from KCl withdrawal-induced apoptosis, suggesting that cell cycle components play a significant role in the death of these neurons. Analysis of the different cell cycle regulatory elements in this model revealed that apoptosis is preceded by an increase in the level of cyclin E protein, with elevated nuclear levels of cyclin D1 and with enhanced activity of the cyclin D1- and E- associated kinases. In addition, there was a significant decrease in the level of the cyclin-dependent kinase (cdk) inhibitor p27. In agreement with these changes, analysis of a major substrate of cyclin-activated cdks, retinoblastoma protein (Rb), showed an increase in the level of phosphorylated forms within 1 hr of KCl withdrawal. Moreover, the overall levels of Rb protein were significantly reduced within 6-12 hr of KCl withdrawal and did so by a caspase-independent mechanism. All of these responses were blocked by cdk inhibitors. These findings indicate that cdks act at an early step in the pathway by which KCl withdrawal induces apoptotic death of cerebellar granule cells and suggest that additional elements of the cell cycle machinery participate in this mechanism.  (+info)

Distinct roles for PP1 and PP2A in phosphorylation of the retinoblastoma protein. PP2a regulates the activities of G(1) cyclin-dependent kinases. (8/94)

The function of the retinoblastoma protein (pRB) in controlling the G(1) to S transition is regulated by phosphorylation and dephosphorylation on serine and threonine residues. While the roles of cyclin-dependent kinases in phosphorylating and inactivating pRB have been characterized in detail, the roles of protein phosphatases in regulating the G(1)/S transition are not as well understood. We used cell-permeable inhibitors of protein phosphatases 1 and 2A to assess the contributions of these phosphatases in regulating cyclin-dependent kinase activity and pRB phosphorylation. Treating asynchronously growing Balb/c 3T3 cells with PP2A-selective concentrations of either okadaic acid or calyculin A caused a time- and dose-dependent decrease in pRB phosphorylation. Okadaic acid and calyculin A had no effect on pRB phosphatase activity even though PP2A was completely inhibited. The decrease in pRB phosphorylation correlated with inhibitor-induced suppression of G(1) cyclin-dependent kinases including CDK2, CDK4, and CDK6. The inhibitors also caused decreases in the levels of cyclin D2 and cyclin E, and induction of the cyclin-dependent kinase inhibitors p21(Cip1) and p27(Kip1). The decrease in cyclin-dependent kinase activities were not dependent on induction of cyclin-dependent kinase inhibitors since CDK inhibition still occurred in the presence of actinomycin D or cycloheximide. In contrast, selective inhibition of protein phosphatase 1 with tautomycin inhibited pRB phosphatase activity and maintained pRB in a highly phosphorylated state. The results show that protein phosphatase 1 and protein phosphatase 2A, or 2A-like phosphatases, play distinct roles in regulating pRB function. Protein phosphatase 1 is associated with the direct dephosphorylation of pRB while protein phosphatase 2A is involved in pathways regulating G(1) cyclin-dependent kinase activity.  (+info)

The adaptive trial design of this advanced Phase II study incorporates (i) a dosing schedule based on the patients estimated tumor burden and not on standard dosing per kilogram body weight or body surface area, and (2) a tumor response evaluation process that is unique to the manner in which osteosarcoma responds favorably to therapy, i.e., with necrosis and increasing calcification in metastatic tumors and decreased glucose utilization using PET-CT imaging studies.. Twenty to thirty patients will receive Rexin-G at either Dose Level 1 or 2. Patients will be assigned a dose level based on the estimated tumor burden as measured by PET-CT imaging studies. Estimated tumor burden is measured by multiplying the sum of the longest diameters of target lesions in cm by 10e9 cancer cells. If the tumor burden is less than 10 billion cells, the patient will be assigned to Dose Level 1, if the tumor burden is greater than 10 billion cells, the patient will be assigned to Dose Level 2.. *Treatment Cycle ...
Cyclin G1, 0.1 mg. Cyclins are the regulatory subunits of Cdc2 p34 and related cyclin-dependent kinases (Cdks) which play critical roles in the control of cell cycle progression.
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Hgc to high - My ultrasound only saw a sack my doctor called me and said my Hgc is to high above 4000 what does it mean? - Welcome to Circle of Moms!!
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SAN MARINO, Calif. and MANILA, Philippines - Nov. 6 (SEND2PRESS NEWSWIRE) -- Epeius Biotechnologies today announced the publication of clinical data from studies conducted at the University of the Philippines, Asian Hospital and Medical Center, Makati Medical Center, Manila, Philippines and Lutheran Medical Center, New York, USA, revealing the safety and single agent efficacy of Rexin-G(TM) for the treatment of a broad spectrum of chemotherapy-resistant cancers. - News from Epeius Biotechnologies Corporation, issued by Send2Press Newswire
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 ...
CCNG2 gene was initially identified in 1996 and encodes for a protein that belongs to a family of cyclins homologous to CCNG1 (7). Previous studies have reported that CCNG2 participates in carcinogenesis and is a known tumor suppressor gene (15-17,20-26). CCNG2 gene expression is downregulated in thyroid (20), oral (21), ovarian (22), breast (23,24), gastric (16), esophageal (17), prostate (25), kidney (26) and colorectal (15) cancer cells.. Several aspects of CCNG2 behavior are associated with antitumor effects. Antitumor agents induce CCNG2 expression, which results in the inhibition of cancer cell proliferation (8-10). In breast cancer, CCNG2 knockdown induces multidrug resistance (8). In colorectal cancer, CCNG2 expression correlates with the tumor stage, lymph node metastasis, clinical stage, histological grade and overall survival (15). In gastric cancer, CCNG2 expression correlates with the extent of differentiation: CCNG2 expression is high in well-differentiated adenocarcinomas and low ...
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As of late, individuals are turning into increasingly health aware. Jadhav, U. & Jameson, J. L. Steroidogenic issue-1 (sf-1)-driven differentiation of murine embryonic stem (es) cells right into a gonadal lineage. Any steered medical therapies must be discussed with your physician. 1: Differentiation-induced pluripotent stem cells (iPSCs) into Leydig-like cells (iPSC-LCs) based on molecular compounds.. People on a ketogenic diet eat 50 grams or fewer of carbohydrates per day and as an alternative eat greater-than-regular amounts of fats and protein. Ge, R. S. & Hardy, M. P. Decreased cyclin a2 and increased cyclin g1 levels coincide with loss of proliferative capability in rat leydig cells throughout pubertal growth.. The main focus of public well being interventions is to forestall and manage ailments, accidents and different health conditions through surveillance of cases and the promotion of healthy conduct , communities , and (in points relevant to human well being) environments Its aim is ...
Got blood test results back for the 3rd blood test I have had in about two weeks or so. First two where great with posotive reading & hormone level was good. Had to have 3rd blood test yesterday, got results back today. I cant work
Students choose 60 credits of modules: they do not have to take Dehonglir Gorffennol/Debating History but it does remain an option. Students must take at least one general module (code beginning HGH/HGC/HGW) over levels 5 and 6 as a whole ...
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/ ... which he showed mediates conjugation of ubiquitin onto G1 cyclin proteins in yeast cells.[5] ... they established that an early step in the release of Cdc14 from Net1 is the phosphorylation of Net1 by the mitotic cyclin-Cdk ...
"CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle progression". Cell. 151 (6): 1308-18. doi: ...
Bose P, Simmons GL, Grant S (2013). "Cyclin-dependent kinase inhibitor therapy for hematologic malignancies". Expert Opin ... Jain SK, Bharate SB, Vishwakarma RA (2012). "Cyclin-dependent kinase inhibition by flavoalkaloids". Mini Rev Med Chem. 12 (7): ...
1994). "p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest ... 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 ...
Bose P, Simmons GL, Grant S (Jun 2013). "Cyclin-dependent kinase inhibitor therapy for hematologic malignancies". Expert ... Martin MP, Olesen SH, Georg GI, Schönbrunn E (Nov 2013). "Cyclin-dependent kinase inhibitor dinaciclib interacts with the ... Fu W, Ma L, Chu B, Wang X, Bui MM, Gemmer J, Altiok S, Pledger WJ (Jun 2011). "The cyclin-dependent kinase inhibitor SCH 727965 ... Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. Dinaciclib ( ...
Cyclin dependent kinases (CDKs) are a group of several different kinases involved in regulation of the cell cycle. They ... Garrington, TP; Johnson, GL (Apr 1999). "Organization and regulation of mitogen-activated protein kinase signaling pathways". ... 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 ...
Therefore, Akt promotes G1 phase progression in a positive feedback loop. Akt promotes cyclin D1 translation via indirect ... Akt promotes G1-S phase cell cycle progression by phosphorylating and inactivating glycogen synthase kinase 3 (GSK-3) at Ser9. ... Alao JP (2007). "The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic ... Akt both indirectly and directly regulates cyclin-dependent kinase (CDK) inhibitors p21Cip1 and p27Kip1 , allowing cell cycle ...
... which regulate the Cyclin E-Cdk2 complex, which inhibits Rb, forming a positive feedback loop, keeping the cell in G1 until the ... The G1/S Checkpoint[edit]. Rb and p53 regulate the transition between G1 and S phase, arresting the cell cycle before DNA ... Rb is inactivated (thereby allowing the G1/S transition to progress unimpeded) by different but analogous viral oncoproteins. ... which plays a central role in the G1/S checkpoint, as well as Rb, which, though downstream of it, is typically kept active by a ...
G1/S-specific cyclin Cln3 is a protein that is encoded by the CLN3 gene. The Cln3 protein is a budding yeast G1 cyclin that ... This showed that the three G1 cyclins were responsible for controlling Start entry in budding yeast. The three G1 cyclins ... Although all three G1 cyclins are necessary for normal regulation of Start and the G1-S transition, Cln3 activity seems to be ... "Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 may be an upstream activator of Cln1, Cln2 and other cyclins". The ...
Cyclin E dsRNA arrested the cell cycle at the G1 phase (before the S phase). Therefore, RNAi can target endogenous genes. In ... cyclin E dsRNA only diminished cyclin E RNA - a similar result was also shown using dsRNA corresponding to cyclin A which acts ... Cells transfected with cyclin E dsRNAs only showed degradation in cyclin E transcripts - the lacZ transcripts were stable. ... Sen GL & Blau HM (2005). "Argonaute2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies". Nature Cell ...
When the cell commits to a new cell cycle, after passing through the Start checkpoint, G1 and G1/S cyclin CDK complexes are ... Removal of cyclin E with antibodies blocks replication. Cyclin E-CDk2 is also important in Drosophila. Levels of cyclin E rise ... Its activity is low in G1, increases in late G1, and remains high till late mitosis. Dbf4 is the key regulator of Cdc7 activity ... In S. cerevisiae, the S cyclins Clb5 and Clb6 play and important role in inititating replication. In frog embryos, cyclin E- ...
The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. „Cell". 75 (4), s. 805-816, 1993. ... Regulation of cyclin A-Cdk2 by SCF component Skp1 and F-box protein Skp2. „Mol. Cell. Biol.". 19 (1), s. 635-45, 1999. PMID: ... Li Y, Jenkins CW, Nichols MA, Xiong Y. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. „ ... Watanabe H, Pan ZQ, Schreiber-Agus N, DePinho RA, Hurwitz J, Xiong Y. Suppression of cell transformation by the cyclin- ...
Zhao L, Samuels T, Winckler S, Korgaonkar C, Tompkins V, Horne MC, Quelle DE (January 2003). "Cyclin G1 has growth inhibitory ... Ravi R, Mookerjee B, Bhujwalla ZM, Sutter CH, Artemov D, Zeng Q, Dillehay LE, Madan A, Semenza GL, Bedi A (January 2000). " ... "The MDM2 C-terminal region binds to TAFII250 and is required for MDM2 regulation of the cyclin A promoter". The Journal of ...
... but p27Kip1 inhibits G1 cyclins and not cyclin B. There are several human diseases that are linked to p27Kip1 and other cyclin ... S-phase cyclins use RXL docking while G1 cyclins use LLPP docking. Sic1 phosphorylation increases when the RXL motif of Clb5 is ... Sic1 phosphorylation is initiated by the G1 cyclins, Cln1,2, and then completed by S-phase cyclins, Clb5,6 (Fig. 1). The ... At the START point in the yeast cell cycle, the G1-cyclins Cln3, Cln1 and Cln 2 activate Cdc28. The activated complex will ...
It reduces the growth of new cells by inhibiting cyclin D1. As a result, cells arrest during G1 phase and enter apoptosis. ... "Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin D1". J. Biol. Chem. 277 (19): 16464-9. doi: ...
"Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1". Science. 284 (5414): 662-5. doi:10.1126 ... Maeda I, Ohta T, Koizumi H, Fukuda M (Apr 2001). "In vitro ubiquitination of cyclin D1 by ROC1-CUL1 and ROC1-CUL3". FEBS ...
The APC/CCdc20 does not recognize G1/S cyclins. Their concentration rises during G1, activating G1/S Cdks, which in turn ... The two main targets of the APC/C are the S/M cyclins and the protein securin. S/M cyclins activate cyclin-dependent kinases ( ... Multiple different mechanisms inhibit Cdks in G1: Cdk inhibitor proteins are expressed, and cyclin gene expression is down- ... It also targets S and M-phase (S/M) cyclins for destruction, which inactivates S/M cyclin-dependent kinases (Cdks) and allows ...
G1/S transition of mitotic cell cycle. • negative regulation of cyclin-dependent protein serine/threonine kinase activity ... regulation of cyclin-dependent protein serine/threonine kinase activity. • negative regulation of G1/S transition of mitotic ... The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and ... cyclin-dependent protein serine/threonine kinase regulator activity. • protein binding. • ATP binding. • cyclin binding. • ...
... and cyclin E Genes Reveal Distinct Roles for the E2F-DP Transcription Factor and Cyclin E during the G1-S Transition". ... Duronio RJ; O'Farrell PH (1995). "Developmental control of the G1 to S transition in Drosophila: Cyclin E is a limiting ... In the context of endoreplication these events are facilitated by an oscillation in cyclin E-Cdk2 activity. Cyclin E-Cdk2 ... de Nooij JC; Graber KH; Hariharan IK (2001). "Expression of cyclin-dependent kinase inhibitor Dacapo is regulated by cyclin E ...
... which can be recognized by the ubiquitin ligase enzyme which destroys the cyclins when appropriate. During G1 and S phase, the ... 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. ...
Furuta H, Horikawa Y, Iwasaki N, Hara M, Sussel L, Le Beau MM, Davis EM, Ogata M, Iwamoto Y, German MS, Bell GI (August 1998 ... Ratineau C, Petry MW, Mutoh H, Leiter AB (March 2002). "Cyclin D1 represses the basic helix-loop-helix transcription factor, ... Fajans SS, Bell GI, Polonsky KS (September 2001). "Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes ... Ratineau C, Petry MW, Mutoh H, Leiter AB (March 2002). "Cyclin D1 represses the basic helix-loop-helix transcription factor, ...
Xiao ZX, Ginsberg D, Ewen M, Livingston DM (1996). "Regulation of the retinoblastoma protein-related protein p107 by G1 cyclin- ... cyclins and cyclin dependent kinases". Oncogene. 15 (2): 143-57. doi:10.1038/sj.onc.1201252. PMID 9244350. Müller H, Moroni MC ...
"Regulation of the retinoblastoma protein-related protein p107 by G1 cyclin-associated kinases". Proceedings of the National ... Retinoblastoma-like protein 1 has been shown to interact with: BEGAIN, BRCA1, BRF1, Cyclin A2, Cyclin-dependent kinase 2, E2F1 ... "Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4". Molecular and ... Shanahan F, Seghezzi W, Parry D, Mahony D, Lees E (Feb 1999). "Cyclin E associates with BAF155 and BRG1, components of the ...
Sic1 releases SPF from inhibition after it is phosphorylated by G1-cyclin-CDK. The phosphorylation marking SPF for ... The S-phase-promoting factor (SPF) is a CDK-cyclin complex that induces the S-phase (synthesis phase) of the cell cycle. The S- ... Toward the end of the G1 phase of mitosis, an SPF is phosphorylated, causing a biochemical cascade that results in the ... a protein which also is a stoichiometric inhibitor of Cdk1-Clb and B-type cyclins). ...
Voit R, Hoffmann M, Grummt I (1999). "Phosphorylation by G1-specific cdk-cyclin complexes activates the nucleolar transcription ...
2002). "Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin D1". J. Biol. Chem. 277 (19): 16464-9. ...
NPAT activates histone gene expression only after it has been phosphorylated by the G1/S-Cdk cyclin E-Cdk2 in early S phase.[ ... NPAT is also a substrate of cyclin E-Cdk2, which is required for the transition between G1 phase and S phase. ... SLBP are marked for degradation by phosphorylation at two threonine residues by cyclin dependent kinases, possibly cyclin A/ ... This occurs when Whi5 is phosphorylated by Cdc8 which is a G1/S Cdk.[114] Suppression of histone gene expression outside of S ...
Upon the decision to progress past the G1 checkpoint, cyclin D levels rise, and cyclin D forms a complex with CDK4 and CDK6, ... including another cyclin, known as cyclin E, which forms a complex with CDK2. The formation of the cyclin E-CDK2 complex then ... yet the primary cyclin utilized is cyclin B. Cyclin B will serve as reference for discussion of the G2/M checkpoint transition ... Skotheim, Jan M.; Di Talia, Stefano; Siggia, Eric D.; Cross, Frederick R. (17 July 2008). "Positive feedback of G1 cyclins ...
... treatment of quiescent cells with growth factors results in the transcriptional activation of the D-type cyclin genes during G1 ... The human cyclin D3 gene has a TATA-less promoter and a single dominant initiation site. The minimal cyclin D3 promoter ... I have been defining the cis-acting elements and trans-acting factors that control transcription of the human cyclin D3 gene in ... Expression of the members of this family of cyclins, D1, 2 and 3, is spatially and temporally regulated with respect to growth ...
These observations show that cyclin levels can be rate-limiting for G1 progression in mammalian cells and suggest that cyclin ... a cyclin. Related kinases are also required for progression through the G1 phase in higher eukaryotes. The role of cyclins in ... Cyclin-dependent regulation of G1 in mammalian fibroblasts Message Subject. (Your Name) has forwarded a page to you from ... This was found to shorten the duration of G1, decrease cell size, and diminish the serum requirement for the transition from G1 ...
An essential G1 function for cyclin-like proteins in yeast.. Richardson HE1, Wittenberg C, Cross F, Reed SI. ... Cyclins were discovered in marine invertebrates based on their dramatic cell cycle periodicity. Recently, the products of three ... the essential function of Cln proteins was found to be limited to the G1 phase. Furthermore, the ability of the Cln proteins to ... shown to be essential for the G1 to S phase transition in S. cerevisiae. Because of the apparent functional redundancy of these ...
Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 ... The cyclin subunit imparts substrate specificity to the complex. Interacts with ATF5. Interacts with EIF3K. Component of the ... Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, ... Regulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) ...
Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 ... Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, ... Regulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) ... IPR013763. Cyclin-like. IPR036915. Cyclin-like_sf. IPR004367. Cyclin_C-dom. IPR015451. Cyclin_D. IPR006671. Cyclin_N. ...
The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has been implicated in the control of the G1 to S ... cyclin E-Cdk2, cyclin D1-Cdk4, and cyclin D2-Cdk4 complexes. Cotransfection experiments indicate that CIP1 and SV40 T antigen ... CIP1 encodes a novel 21 kd protein that is found in cyclin A, cyclin D1, cyclin E, and Cdk2 immunoprecipitates. p21CIP1 is a ... The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.. Harper JW1, Adami GR, Wei N, ...
These cyclins oscillate during the cell cycle - rise in late G1 and fall in early S phase. The primary function of G1/S cyclin- ... The rise of G1/S cyclins is accompanied by the appearance of the S cyclins (Clb5 and Clb6 in budding yeast), which form S ... The G1 cyclins CLN1 and CLN2, upon transcriptional activation by Cln3 in mid-G1, bind Cdk1 (Cdc28) to complete progression ... Cln1, Cln2, and Cln3 are cyclin proteins expressed in the G1-phase of the cell cycle of budding yeast. Like other cyclins, they ...
Cyclin E / metabolism. Cyclin-Dependent Kinase 2. Cyclin-Dependent Kinase 4. Cyclin-Dependent Kinase Inhibitor p16 / metabolism ... Cyclin-Dependent Kinases / antagonists & inhibitors*, metabolism. Cyclins / metabolism. Dose-Response Relationship, Drug. G1 ... 0/CDKN1A protein, human; 0/Cell Cycle Proteins; 0/Cyclin E; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Cyclin-Dependent Kinase ... EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 3.4. ...
Cyclins are the regulatory subunits of Cdc2 p34 and related cyclin-dependent kinases (Cdks) which play critical roles in the ... The G1 to S transition, however, appears to be controlled by the G1 cyclins. Cyclin D1 accumulates during G1 and associates ... amino acid sequence identity with cyclin G1. Peak expression of cyclin G2 is seen in late S phase, as opposed to cyclin G1 ... Cyclin E and Cdk2 interact during the G1 to S transition. Cyclin G contains a typical N terminal cyclin box and a carboxy ...
... cyclin G1 knockdown in HepG2 cells was obtained with two siRNAs (G1/238 and G1/832). Figure 2C shows a decrease in cyclin G1 ... A decrease of cyclin G1 mRNA was observed with both siRNAs. D, WB analysis of cyclin G1 and p53 expression in G1/832 siRNA- ... cyclin G1 siRNA (G1/832), or negative controls. Original magnification, ×10. B, cell cycle analysis of miR-122 and cyclin G1 ... MiR-122 and cyclin G1 modulate p53 expression. A, WB analysis of cyclin G1 and p53 levels in miR-122 transfected HepG2 cells. A ...
GFP vector and cyclin D3 (Cyclin D3), or PTEN and cyclin D3 (PTEN + Cyclin D3). Twenty-four h after transduction, the DNA ... 250 anti-cyclin D1 (Santa Cruz Biotechnology); 1:250 anti-cyclin D2 (Santa Cruz Biotechnology); or 1:250 anti-cyclin D3 (Santa ... Toyoshima H., Hunter T. p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell, 78: 67-74, ... Matsushime H., Roussel M. F., Ashmun R. A., Sherr C. J. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase ...
Top performende anti-Schwein Cyclin G1 Antikörper für Immunohistochemistry (Paraffin-embedded Sections) (IHC (p)) vergleichen ... Cyclin G1 (CCNG1 Antibody Abstract) Hintergrund Name/Gene ID: CCNG1. Synonyms: CCNG1, CCNG, Cyclin G1, CYCG1, Cyclin-G, Cyclin- ... Recommended Cyclin G1 Antibody (geliefert von: Anmelden zum Anzeigen ) Antigen Cyclin G1 (CCNG1) Antikörper Synonyme für dieses ... Target Details Cyclin G1 Anwendungsinformationen Handhabung Bilder Spezifität Recognizes endogenous levels of Cyclin G1 protein ...
Gene Set: REACTOME_CYCLIN_E_ASSOCIATED_EVENTS_DURING_G1_S_TRANSITION_. Standard name. REACTOME_CYCLIN_E_ASSOCIATED_EVENTS_ ...
... a G1 cyclin, positively regulates the expression of CLN1 and CLN2, two additional G1 cyclins whose expression during late G1 is ... Activation of CLN1 and CLN2 G1 cyclin gene expression by BCK2.. C J Di Como, H Chang, K T Arndt ... Activation of CLN1 and CLN2 G1 cyclin gene expression by BCK2. Message Subject (Your Name) has forwarded a page to you from ... In the absence of CLN3, bck2 mutations cause an extremely slow growth rate: the cells accumulate in late G1 with very low ...
tr,A0A1J3JA08,A0A1J3JA08_NOCCA Cyclin-dependent kinase B1-2 (Fragment) OS=Noccaea caerulescens OX=107243 GN=MP_TR1527_c0_g1_i1_ ... Cyclin-dependent kinase B1-2Imported. ,p>Information which has been imported from another database using automatic procedures ... ORF Names:MP_TR1527_c0_g1_i1_g.3997Imported. ,p>Information which has been imported from another database using automatic ...
3B, cyclin D1 and cdk-6 alone were able to phosphorylate pRb as were the combinations of cyclin D1 plus cdk-4 or cyclin D1 plus ... Akt induces β-cell proliferation by regulating cyclin d1, cyclin d2, and p21 levels and cyclin-dependent kinase-4 activity. ... We find that in contrast to murine islets which contain little or no cdk-6 (17,23,35,36), each of the four G1/S cyclins and ... Survey of the Human Pancreatic β-Cell G1/S Proteome Reveals a Potential Therapeutic Role for Cdk-6 and Cyclin D1 in Enhancing ...
Effects of different carbon fluxes on G1 phase duration, cyclin expression, and reserve carbohydrate metabolism in ...
Cyclin G1 (CG1), an atypical cyclin, promoted G2-M arrest in PTCs and up-regulated TASCC formation. PTC TASCC formation was ... Cyclin G1 regulates G2-M arrest in proximal tubular cells, promoting a TASCC-induced secretory phenotype, fibrosis, and kidney ... Cyclin G1 regulates G2-M arrest in proximal tubular cells, promoting a TASCC-induced secretory phenotype, fibrosis, and kidney ... Cyclin G1 and TASCC regulate kidney epithelial cell G2-M arrest and fibrotic maladaptive repair ...
G1 cyclins control the G1 to S phase transition in the budding yeast, Saccharomyces cerevisiae. Cyclin E was discovered in the ... Cyclin E-associated kinase activity was correlated with the appearance of complexes containing cyclin E and the cyclin- ... Thus, the cyclin E-Cdk2 complex may constitute a human G1-S phase-specific regulatory protein kinase. ... Association of human cyclin E with a periodic G1-S phase protein kinase ...
MEF-dependent transcription was suppressed by the expression of cyclin A but not by cyclin D or cyclin E. This effect was due ... Cyclin A-CDK2 phosphorylated MEF protein in vitro more efficiently than cyclin D-CDK4 or cyclin E-CDK2, and phosphorylation of ... Cyclin A / metabolism*. DNA Primers. DNA-Binding Proteins / chemistry, metabolism*, physiology. G1 Phase / physiology*. ... These amino acid substitutions also reduced the restriction of MEF activity to G1. Phosphorylation of MEF by the cyclin A-CDK2 ...
Cell cycle control in mammalian cells: role of cyclins, cyclin dependant kinases (CDKs), growth suppressor genes, and cyclin- ... Shapiro GI. Cyclin-dependent pathways as targets for cancer treatment. J Clin Oncol 2006;24:1770-83. ... P276-00, a novel cyclin-dependent inhibitor induces G1-G2 arrest, shows antitumor activity on cisplatin-resistant cells and ... Cdk4/6-cyclin D, Cdk2-cyclin E, and the transcription complex that includes pRb and E2F are pivotal in controlling progression ...
Cyclin G1 antibody LS-C415844 is an unconjugated rabbit polyclonal antibody to Cyclin G1 (CCNG1) from human, mouse and rat. ... CCNG1 Antibody, CCNG Antibody, Cyclin G1 Antibody, CYCG1 Antibody, Cyclin-G Antibody, Cyclin-G1 Antibody ... Cyclin G1 antibody LS-C415844 is an unconjugated rabbit polyclonal antibody to Cyclin G1 (CCNG1) from human, mouse and rat. ... Cyclin G1 antibody LS-C415844 is an unconjugated rabbit polyclonal antibody to Cyclin G1 (CCNG1) from human, mouse and rat. ...
... full-length cyclin E (cyclin EL), or LMW cyclin E (cyclin E-T1 and cyclin E-T2). Twenty-four hours later, cells were left ... Altered regulation of G1 cyclins in senescent human diploid fibroblasts: accumulation of inactive cyclin E-cdk2 and cyclin D1-2 ... Low-Molecular-Weight Cyclin E Can Bypass Letrozole-Induced G1 Arrest in Human Breast Cancer Cells and Tumors ... Cyclin E has also been implicated in antiestrogen resistance. A study found that the association between cyclin E and disease ...
1994) Cyclin D1 induction in breast cancer cells shortens G1 and is sufficient for cells arrested in G1 to complete the cell ... NF-κB Function in Growth Control: Regulation of Cyclin D1 Expression and G0/G1-to-S-Phase Transition ... Cyclin E, cyclin D3, CDK2, p27, p21, p16, and p15 were detected as described in Materials and Methods. Similar results were ... 1995) Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 9:1149-1163. ...
Cyclin G1 antibody LS-C481195 is an HRP-conjugated rabbit polyclonal antibody to Cyclin G1 (CCNG1) from human, bat, bovine and ... Cyclin G1 antibody LS-C481195 is an HRP-conjugated rabbit polyclonal antibody to Cyclin G1 (CCNG1) from human, bat, bovine and ... Cyclin G1 antibody LS-C481195 is an HRP-conjugated rabbit polyclonal antibody to Cyclin G1 (CCNG1) from human, bat, bovine and ... CCNG1 / Cyclin G antibody Western blot of MCF7 Cell lysate. Antibody concentration 1 ug/ml. This image was taken for the ...
  • Eukaryotic cells become committed to proliferate during the G1 phase of the cell cycle. (sciencemag.org)
  • These observations show that cyclin levels can be rate-limiting for G1 progression in mammalian cells and suggest that cyclin synthesis may be the target of physiological signals that control cell proliferation. (sciencemag.org)
  • Effects of adenoviruses expressing cdk-6, cdk-4, and cyclin D 1 on proliferation in human β-cells were studied in both invitro and in vivo models. (diabetesjournals.org)
  • Furthermore, we show that cdk-6 and a d -cyclin partner can be used to markedly accelerate replication in human β-cells in vitro. (diabetesjournals.org)
  • Treatment of the cells with roscovitine overcomes the LMW cyclin E-mediated letrozole resistance. (aacrjournals.org)
  • Impaired cell cycle progression of T47D cells expressing an NF-κB superrepressor (IκBαΔN) could be rescued by ectopic expression of cyclin D1. (asm.org)
  • The G1 cyclins, cyclin D1 and E, are rate limiting for progression through G1 phase of the cell cycle in breast epithelial cells and are oncogenic when expressed in the mammary epithelium of transgenic mice. (garvan.org.au)
  • There was no apparent relationship, however, between cyclin D1 expression and the in vitro activity of its major kinase partner, Cdk4, although MDA-MB-134 cells displayed the highest level of both cyclin D1 expression and Cdk4 activity. (garvan.org.au)
  • When differentiated G0-arrested cells were induced to reenter the cell cycle in the G1 phase and resume cell division by treatment with plant hormones, cycMs3 transcript levels increased long before the onset of DNA synthesis. (plantcell.org)
  • We propose that CycMs3 helps control reentry of quiescent G0-arrested cells into the G1 phase of the cell cycle. (plantcell.org)
  • Yeast cells become committed to the mitotic cell cycle at a stage during G1 called Start. (ox.ac.uk)
  • The consequences of this negative regulation were most apparent in clb6 mutants, which had a shorter pre-Start G1 phase as well as a shorter G2 phase than congenic wild-type cells. (mysciencework.com)
  • RNAi-mediated knockdown of FBXO31 prevents cells from undergoing efficient arrest in G1 after gamma-irradiation and markedly increases sensitivity to DNA damage. (umassmed.edu)
  • Cyclins can be divided into four classes based on their behavior in the cell cycle of vertebrate somatic cells and yeast cells: G1 cyclins, G1/S cyclins, S cyclins, and M cyclins. (wikipedia.org)
  • Expression of cyclins detected immunocytochemically in individual cells in relation to cellular DNA content (cell cycle phase), or in relation to initiation and termination of DNA replication during S-phase, can be measured by flow cytometry . (wikipedia.org)
  • CARI III demonstrates anti-proliferative activity against B16F10 melanoma cells through inducing G0/G1 cell cycle arrest. (mdpi.com)
  • Here, we show, using a tetracycline-regulated system, that expression of wild-type p21 in p53-deficient DLD1 human colon cancer cells inhibits DNA synthesis and causes G1 and G2 cell cycle arrest. (mendeley.com)
  • 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. (nature.com)
  • The expression of CDK4, cyclin D1, and phospho-Rb was markedly decreased in the A549-shTGIF cells compared with the A549-shcon cells, and p21 was markedly increased in the A549-shTGIF cells compared with the A549-shcon cells. (springer.com)
  • Moreover, cyclin G1 was up-regulated by E2 and/or progesterone in MCF-7 cells . (bvsalud.org)
  • After knockdown of cyclin G1 in MCF-7 cells using a specific shRNA , estradiol - and progesterone -mediated cell viability and clonogenic ability were significantly limited. (bvsalud.org)
  • PD-0332991 treatment blocked RB phosphorylation and inhibited cell growth through the induction of G1 arrest of colorectal carcinoma cells. (duhnnae.com)
  • Recombinant cyclin/CDK holoenzymes were purified from Sf9 cells engineered to produce baculoviruses that express a specific cyclin or CDK. (aacrjournals.org)
  • The cell cycle is the process by which mammalian cells regulate proliferation and has S, M, G2 and G1 phase. (omicsonline.org)
  • M phase (DNA and cellular components division into 2 daughter cells) and G1 phase (cells commit and prepare for another round of replication) [ 1 - 3 ]. (omicsonline.org)
  • During G1 (or gap 1) cells grow in size, and respond to signals from outside the cell. (madsci.org)
  • Some cells, like nerve and muscle cells, never divide and spend their entire lives in G1. (madsci.org)
  • After the cell escapes from G1 into S phase, it is usually going to go through the whole cell cycle and make two cells. (madsci.org)
  • Nuclear targeting of 4.1N arrests PC12 cells at G1 phase. (jneurosci.org)
  • Although detailed mechanisms remain to be explored, selective blockage of tumor cells in G0/G1 phase accompanied by p53-associated apoptosis makes tetrazolium violet a promising anticancer agent, meriting further investigations. (springer.com)
  • Cyclin D1, which is a key cell cycle regulator, was significantly decreased in GIT1 KO cells. (ahajournals.org)
  • Cyclin D1 staining of HCT116 cells using Alexa Fluor 647 conjugated Cyclin D1 antibody. (novusbio.com)
  • Cyclin D1 as well as D2 and D3 have central roles in linking exogenous growth regulating stimuli with the cycling machinery of cells. (novusbio.com)
  • The canonical Restriction Point model suggests that cells are born into a state in which they are uncommitted to the cell cycle, but will activate cyclin-dependent kinase 2 and cross the Restriction Point several hours later if sufficient nutrients are available. (pnas.org)
  • Based on these data, a model emerged that both cycling cells and cells emerging from serum starvation were subject to a mid- to late-G1 Restriction Point. (pnas.org)
  • The whi3 mutant has small cells, while extra doses of WHI3 produce large cells, and a large excess of WHI3 produces a lethal arrest in G1 phase. (genetics.org)
  • In small G1 cells, the only cyclin known to be present is Cln3, which is expressed relatively constitutively through the cell cycle. (genetics.org)
  • Here we employ species-specific antibodies to monitor changes in quantity and location of four maize cyclins and maize Cdc2-kinase in dividing maize root tip cells. (deepdyve.com)
  • Persistence of mitotic cyclins and CDK after mitosis into the cytokinetic stage, as seen in maize, is not paralleled in animal cells, where the cytokinetic mid-body is not so labelled, presumably reflecting the key role of the phragmoplast apparatus in plant cell division. (deepdyve.com)
  • In part, this coordination is achieved through integration of extracellular signals during the G1 phase, to which cells respond by either advancing into or withdrawing from another division cycle ( Pardee, 1989 ). (biologists.org)
  • Thus, substitution of aspartic acid 199 with alanine in ICP0 abolished stabilization of cyclin D3, reduced the yields of virus from resting cells, and reduced the capacity of the virus to invade the mouse central nervous system from a peripheral site. (asm.org)
  • Because cyclin A2 was stimulated by cAMP, we assessed the role of cylcin A2 in cell cycle progression in Min6 and isolated islet β-cells. (diabetesjournals.org)
  • In Min6 cells, cyclin A2 knockdown prevented exendin-4-stimulated proliferation. (diabetesjournals.org)
  • The duration of each phase, including the G1 phase, is different in many different types of cells. (wikipedia.org)
  • In human somatic cells, the cell cycle lasts about 18 hours, and the G1 phase takes up about 1/3 of that time. (wikipedia.org)
  • Members of the retinoblastoma (Rb) tumor-suppressor family (pRb, p107 and p130 in mammals) have been found to inhibit progression through the G1 phase ( Sherr, 1996 ). (biologists.org)
  • Detailed analysis of the molecular mechanism of ATRA-induced cell cycle arrest and differentiation showed that the onset of cell cycle arrest was associated with a decrease in c-Myc and cyclin E levels and upregulation of p27 Kip1 and p21 WAF1/CIP1 . (diva-portal.org)
  • Our results demonstrate that blockage of K + channels and cell depolarization induce G1 arrest in the OP cell cycle through a mechanism that may involve p27 Kip1 and p21 CIP1 and further support the conclusion that OP cell cycle arrest and differentiation are two uncoupled events. (jneurosci.org)
  • The D-type cyclins are induced as part of the delayed early response to mitogenic stimulation by growth factors, form active holoenzymes with CDK4 or CDK6 by mid-G 1 , and are able to bind directly to pRB via their N-terminal L-X-C-X-E motifs. (asm.org)
  • Kaposi sarcoma herpesvirus ( KSHV ) encodes a D-type cyclin (ORF72) that binds CDK6 and is likely to contribute to KSHV-related cancers . (wikipedia.org)
  • D-type cyclins (D1, D2, and D3) are G1-specific cyclins that associate with CDK4 or CDK6, and promote restriction point progression during G1 phase ( Sherr, 1993 ). (pubmedcentralcanada.ca)
  • The cyclin subunit imparts substrate specificity to the complex. (rcsb.org)
  • passage through the Restriction Point then occurs in late G1. (pnas.org)
  • After a vertebrate cell has been in the G1 phase for about three hours, the cell enters a restriction point in which it is decided whether the cell will move forward with the G1 phase or move into the dormant G0 phase. (wikipedia.org)
  • Previous genetic analysis has revealed that two B-type cyclins, Clb5 and Clb6, have a positive role in DNA replication. (mysciencework.com)
  • Cyclin II binds to all microtubule arrays during the cell cycle, becoming markedly concentrated in the phragmoplast, and cyclin III associates with the spindle and then the phragmoplast. (deepdyve.com)
  • The studies described in this report stemmed from the observation that the infected cell protein No.0 (ICP0) of herpes simplex virus 1 (HSV-1) binds to and stabilizes cyclin D3 ( 18 ). (asm.org)
  • This was followed by a rapid fall in cyclin A and B and a coordinate dephosphorylation of the retinoblastoma protein (pRb). (diva-portal.org)