Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.
A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.
A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.
A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.
A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
A cyclin D subtype which is regulated by GATA4 TRANSCRIPTION FACTOR. Experiments using KNOCKOUT MICE suggest a role for cyclin D2 in granulosa cell proliferation and gonadal development.
A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.
A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.
A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.
A cyclin subtype that is specific for CYCLIN-DEPENDENT KINASE 4 and CYCLIN-DEPENDENT KINASE 6. Unlike most cyclins, cyclin D expression is not cyclical, but rather it is expressed in response to proliferative signals. Cyclin D may therefore play a role in cellular responses to mitogenic signals.
A cyclin G subtype that is constitutively expressed throughout the cell cycle. Cyclin G1 is considered a major transcriptional target of TUMOR SUPPRESSOR PROTEIN P53 and is highly induced in response to DNA damage.
A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.
A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.
A 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.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
A cyclin B subtype that colocalizes with GOLGI APPARATUS during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 9. Unlike traditional cyclins, which regulate the CELL CYCLE, type T cyclins appear to regulate transcription and are components of positive transcriptional elongation factor B.
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.
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.
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.
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 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.
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.
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.
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.
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.
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.
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.
Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.
A 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.
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.
Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).
The B-cell leukemia/lymphoma-1 genes, associated with various neoplasms when overexpressed. Overexpression results from the t(11;14) translocation, which is characteristic of mantle zone-derived B-cell lymphomas. The human c-bcl-1 gene is located at 11q13 on the long arm of chromosome 11.
A 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 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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
A cell line derived from cultured tumor cells.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.
A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.
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.
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.
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)
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.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
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.
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.
An aspect of protein kinase (EC in which serine residues in protamines and histones are phosphorylated in the presence of ATP.
A quiescent state of cells during G1 PHASE.
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
Protein kinase that drives both the mitotic and meiotic cycles in all eukaryotic organisms. In meiosis it induces immature oocytes to undergo meiotic maturation. In mitosis it has a role in the G2/M phase transition. Once activated by CYCLINS; MPF directly phosphorylates some of the proteins involved in nuclear envelope breakdown, chromosome condensation, spindle assembly, and the degradation of cyclins. The catalytic subunit of MPF is PROTEIN P34CDC2.
A 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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
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.
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.
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.
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.
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.
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.
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 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.
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.
Echinoderms having bodies of usually five radially disposed arms coalescing at the center.
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.
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.
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.
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.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
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.
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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
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).
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.
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.
A protein kinase encoded by the Saccharomyces cerevisiae CDC28 gene and required for progression from the G1 PHASE to the S PHASE in the CELL CYCLE.
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.
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.
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.
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.
Tumors or cancer of the human BREAST.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).
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).
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.
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
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells.
Proteins obtained from various species of Xenopus. Included here are proteins from the African clawed frog (XENOPUS LAEVIS). Many of these proteins have been the subject of scientific investigations in the area of MORPHOGENESIS and development.
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.
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.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
A CYCLIN C dependent kinase that is an important component of the mediator complex. The enzyme is activated by its interaction with CYCLIN C and plays a role in transcriptional regulation by phosphorylating RNA POLYMERASE II.
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.
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.
The process by which a DNA molecule is duplicated.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Cdh1 is an activator of the anaphase-promoting complex-cyclosome, and is involved in substrate recognition. It associates with the complex in late MITOSIS from anaphase through G1 to regulate activity of CYCLIN-DEPENDENT KINASES and to prevent premature DNA replication.
A cyclin-dependent kinase that forms a complex with CYCLIN C and is active during the G1 PHASE of the CELL CYCLE. It plays a role in the transition from G1 to S PHASE and in transcriptional regulation.
Elements of limited time intervals, contributing to particular results or situations.
Transport proteins that carry specific substances in the blood or across cell membranes.
Cellular proteins encoded by the c-mos genes (GENES, MOS). They function in the cell cycle to maintain MATURATION PROMOTING FACTOR in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time.
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.
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.
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.
The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs).
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.
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.
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.
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.
The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the SPINDLE APPARATUS prior to separation.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
A 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.
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.
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.
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.
A transcriptional elongation factor complex that is comprised of a heterodimer of CYCLIN-DEPENDENT KINASE 9 and one of several CYCLINS including TYPE T CYCLINS and cyclin K. It functions by phosphorylating the carboxy-terminal domain of RNA POLYMERASE II.
The cell center, consisting of a pair of CENTRIOLES surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (MITOTIC SPINDLE APPARATUS).
The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
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).
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)
A subset of ubiquitin protein ligases that are formed by the association of a SKP DOMAIN PROTEIN, a CULLIN DOMAIN PROTEIN and a F-BOX DOMAIN PROTEIN.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
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.
A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.
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.
Securin is involved in the control of the metaphase-anaphase transition during MITOSIS. It promotes the onset of anaphase by blocking SEPARASE function and preventing proteolysis of cohesin and separation of sister CHROMATIDS. Overexpression of securin is associated with NEOPLASTIC CELL TRANSFORMATION and tumor formation.
An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN-LIKE REPEATS. Aberrant expression of this protein has been associated with deregulated EPITHELIAL CELL growth, organ enlargement, and a variety of NEOPLASMS.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.
Proteins prepared by recombinant DNA technology.
A potent inhibitor of CYCLIN-DEPENDENT KINASES in G1 PHASE and S PHASE. In humans, aberrant expression of p57 is associated with various NEOPLASMS as well as with BECKWITH-WIEDEMANN SYNDROME.
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.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
Gated transport mechanisms by which proteins or RNA are moved across the NUCLEAR MEMBRANE.
An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN REPEATS. Aberrant expression of this protein has been associated with TESTICULAR CANCER.
A microtubule structure that forms during CELL DIVISION. It consists of two SPINDLE POLES, and sets of MICROTUBULES that may include the astral microtubules, the polar microtubules, and the kinetochore microtubules.
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.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A mature haploid female germ cell extruded from the OVARY at OVULATION.
The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.
The phosphoric acid ester of threonine. Used as an identifier in the analysis of peptides, proteins, and enzymes.
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.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
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)
Highly conserved proteins that specifically bind to and activate the anaphase-promoting complex-cyclosome, promoting ubiquitination and proteolysis of cell-cycle-regulatory proteins. Cdc20 is essential for anaphase-promoting complex activity, initiation of anaphase, and cyclin proteolysis during mitosis.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
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.
Family of retrovirus-associated DNA sequences (myc) originally isolated from an avian myelocytomatosis virus. The proto-oncogene myc (c-myc) codes for a nuclear protein which is involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Truncation of the first exon, which appears to regulate c-myc expression, is crucial for tumorigenicity. The human c-myc gene is located at 8q24 on the long arm of chromosome 8.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
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.
The developmental entity of a fertilized egg (ZYGOTE) in animal species other than MAMMALS. For chickens, use CHICK EMBRYO.
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.
Genes that code for proteins that regulate the CELL DIVISION CYCLE. These genes form a regulatory network that culminates in the onset of MITOSIS by activating the p34cdc2 protein (PROTEIN P34CDC2).
Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.
The phase of cell nucleus division following PROPHASE, when the breakdown of the NUCLEAR ENVELOPE occurs and the MITOTIC SPINDLE APPARATUS enters the nuclear region and attaches to the KINETOCHORES.
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.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
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).
Proteins found in any species of fungus.
Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.
A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.
MAMMARY GLANDS in the non-human MAMMALS.
The first phase of cell nucleus division, in which the CHROMOSOMES become visible, the CELL NUCLEUS starts to lose its identity, the SPINDLE APPARATUS appears, and the CENTRIOLES migrate toward opposite poles.
Agents that inhibit PROTEIN KINASES.
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.
Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.
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.
Preparations of cell constituents or subcellular materials, isolates, or substances.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.

Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (1/908)

The irreversible G1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). We show that the Cdk inhibitor p21(Sdi1,Cip1,Waf1), which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active. Furthermore, the senescent-cell-cycle arrest occurs prior to the accumulation of the Cdk4-Cdk6 inhibitor p16(Ink4a), suggesting that p21 may be sufficient for this event. Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16. Instead, the cyclin D1-Cdk4 and cyclin D1-Cdk6 complexes in these cells are associated with an increased amount of p21, suggesting that p21 may be responsible for inactivation of both cyclin E- and cyclin D1-associated kinase activity at the early stage of senescence. Moreover, even in the late stage of senescence when p16 is high, cyclin D1-Cdk4 complexes are persistent, albeit reduced by +info)

Progesterone inhibits estrogen-induced cyclin D1 and cdk4 nuclear translocation, cyclin E- and cyclin A-cdk2 kinase activation, and cell proliferation in uterine epithelial cells in mice. (2/908)

The response of the uterine epithelium to female sex steroid hormones provides an excellent model to study cell proliferation in vivo since both stimulation and inhibition of cell proliferation can be studied. Thus, when administered to ovariectomized adult mice 17beta-estradiol (E2) stimulates a synchronized wave of DNA synthesis and cell division in the epithelial cells, while pretreatment with progesterone (P4) completely inhibits this E2-induced cell proliferation. Using a simple method to isolate the uterine epithelium with high purity, we have shown that E2 treatment induces a relocalization of cyclin D1 and, to a lesser extent, cdk4 from the cytoplasm into the nucleus and results in the orderly activation of cyclin E- and cyclin A-cdk2 kinases and hyperphosphorylation of pRb and p107. P4 pretreatment did not alter overall levels of cyclin D1, cdk4, or cdk6 nor their associated kinase activities but instead inhibited the E2-induced nuclear localization of cyclin D1 to below the control level and, to a lesser extent, nuclear cdk4 levels, with a consequent inhibition of pRb and p107 phosphorylation. In addition, it abrogated E2-induced cyclin E-cdk2 activation by dephosphorylation of cdk2, followed by inhibition of cyclin A expression and consequently of cyclin A-cdk2 kinase activity and further inhibition of phosphorylation of pRb and p107. P4 is used therapeutically to oppose the effect of E2 during hormone replacement therapy and in the treatment of uterine adenocarcinoma. This study showing a novel mechanism of cell cycle inhibition by P4 may provide the basis for the development of new antiestrogens.  (+info)

Functions of cyclin A1 in the cell cycle and its interactions with transcription factor E2F-1 and the Rb family of proteins. (3/908)

Human cyclin A1, a newly discovered cyclin, is expressed in testis and is thought to function in the meiotic cell cycle. Here, we show that the expression of human cyclin A1 and cyclin A1-associated kinase activities was regulated during the mitotic cell cycle. In the osteosarcoma cell line MG63, cyclin A1 mRNA and protein were present at very low levels in cells at the G0 phase. They increased during the progression of the cell cycle and reached the highest levels in the S and G2/M phases. Furthermore, the cyclin A1-associated histone H1 kinase activity peaked at the G2/M phase. We report that cyclin A1 could bind to important cell cycle regulators: the Rb family of proteins, the transcription factor E2F-1, and the p21 family of proteins. The in vitro interaction of cyclin A1 with E2F-1 was greatly enhanced when cyclin A1 was complexed with CDK2. Associations of cyclin A1 with Rb and E2F-1 were observed in vivo in several cell lines. When cyclin A1 was coexpressed with CDK2 in sf9 insect cells, the CDK2-cyclin A1 complex had kinase activities for histone H1, E2F-1, and the Rb family of proteins. Our results suggest that the Rb family of proteins and E2F-1 may be important targets for phosphorylation by the cyclin A1-associated kinase. Cyclin A1 may function in the mitotic cell cycle in certain cells.  (+info)

Leukemia translocation protein PLZF inhibits cell growth and expression of cyclin A. (4/908)

The PLZF gene was identified by its fusion with the RARalpha locus in a therapy resistant form of acute promyelocytic leukemia (APL) associated with the t(11;17)(q23;q21) translocation. Here we describe PLZF as a negative regulator of cell cycle progression ultimately leading to growth suppression. PLZF can bind and repress the cyclin A2 promoter while expression of cyclin A2 reverts the growth suppressed phenotype of myeloid cells expressing PLZF. In contrast RARalpha-PLZF, a fusion protein generated in t(11;17)(q23;q21)-APL activates cyclin A2 transcription and allows expression of cyclin A in anchorage-deprived NIH3T3 cells. Therefore, cyclin A2 is a candidate target gene for PLZF and inhibition of cyclin A expression may contribute to the growth suppressive properties of PLZF. Deregulation of cyclin A2 by RARalpha-PLZF may represent an oncogenic mechanism of this chimeric protein and contribute to the aggressive clinical phenotype of t(11;17)(q23;q21)-associated APL.  (+info)

Growth-inhibitory effect of cyclic GMP- and cyclic AMP-dependent vasodilators on rat vascular smooth muscle cells: effect on cell cycle and cyclin expression. (5/908)

1. The possibility that the antiproliferative effect of cyclic GMP- and cyclic AMP-dependent vasodilators involves an impaired progression of vascular smooth muscle cells (VSMC) through the cell cycle and expression of cyclins, which in association with the cyclin-dependent kinases control the transition between the distinct phases of the cell cycle, was examined. 2. FCS (10%) stimulated the transition of quiescent VSMC from the G0/G1 to the S phase (maximum within 18-24 h and then to the G2/M phase (maximum within 22-28 h). Sodium nitroprusside and 8-Br-cyclic GMP, as well as forskolin and 8-Br-cyclic AMP markedly reduced the percentage of cells in the S phase after FCS stimulation. 3. FCS stimulated the low basal protein expression of cyclin D1 (maximum within 8-24 h) and E (maximum within 8-38 h) and of cyclin A (maximum within 14-30 h). The stimulatory effect of FCS on cyclin D1 and A expression was inhibited, but that of cyclin E was only minimally affected by the vasodilators. 4. FCS increased the low basal level of cyclin D1 mRNA after a lag phase of 2 h and that of cyclin A after 12 h. The vasodilators significantly reduced the FCS-stimulated expression of cyclin D1 and A mRNA. 5. These findings indicate that cyclic GMP- and cyclic AMP-dependent vasodilators inhibit the proliferation of VSMC by preventing the progression of the cell cycle from the G0/G1 into the S phase, an effect which can be attributed to the impaired expression of cyclin D1 and A.  (+info)

Adhesion to fibronectin stimulates proliferation of wild-type and bcr/abl-transfected murine hematopoietic cells. (6/908)

Cells of most tissues require adhesion to a surface to grow. However, for hematopoietic cells, both stimulation and inhibition of proliferation by adhesion to extracellular matrix components have been described. Furthermore, it has been suggested that progenitor cells from chronic myelogenous leukemia show decreased beta1 integrin-mediated adhesion to fibronectin, resulting in increased proliferation and abnormal trafficking. However, we show here that the chronic myelogenous leukemia-specific fusion protein p210bcr/abl stimulates the expression of alpha5beta1 integrins and induces adhesion to fibronectin when expressed in the myeloid cell line 32D. Moreover, proliferation of both p210bcr/abl-transfected 32D (32Dp210) cells and untransfected 32D cells is stimulated by immobilized fibronectin. Cell cycle analysis revealed that nonadherent 32D and 32Dp210 cells are arrested in late G1 or early S phase, whereas the adherent fractions continue cycling. Although both adherent and nonadherent p210bcr/abl-transfected and parental 32D cells express equal amounts of cyclin A, a protein necessary for cell cycle progression at the G1/S boundary, cyclin A complexes immunoprecipitated from 32D cells cultured on immobilized fibronectin were found to be catalytically inactive in nonadherent but not in adherent cells. In addition, as compared with untransfected 32D cells, cyclin A immunoprecipitates from 32Dp210 cells exhibited a greatly elevated kinase activity and remained partially active irrespective of the adhesion status. The lack of cyclin A/cyclin-dependent kinase (CDK) 2 activity in nonadherent 32D cells appeared to result from increased expression and cyclin A complex formation of the CDK inhibitor p27(Kip1). Taken together, our results indicate that adhesion stimulates cell cycle progression of hematopoietic cells by down-regulation of p27(Kip1), resulting in activation of cyclin A/CDK2 complexes and subsequent transition through the G1/S adhesion checkpoint.  (+info)

gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle. (7/908)

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder leading to the widespread development of benign tumors that often contain giant cells. We show that the Drosophila gene gigas encodes a homolog of TSC2, a gene mutated in half of TSC patients. Clones of gigas mutant cells induced in imaginal discs differentiate normally to produce adult structures. However, the cells in these clones are enlarged and repeat S phase without entering M phase. Our results suggest that the TSC disorder may result from an underlying defect in cell cycle control. We have also identified a Drosophila homolog of TSC1.  (+info)

Identification and structure characterization of a Cdk inhibitory peptide derived from neuronal-specific Cdk5 activator. (8/908)

The activation of cyclin-dependent kinase 5 (Cdk5) depends on the binding of its neuronal specific activator Nck5a. The minimal activation domain of Nck5a is located in the region of amino acid residues 150 to 291 (Tang, D., Chun, A. C. S., Zhang, M., and Wang, J. H. (1997) J. Biol. Chem. 272, 12318-12327). In this work we show that a 29-residue peptide, denoted as the alphaN peptide, encompassing amino acid residues Gln145 to Asp173 of Nck5a is capable of binding Cdk5 to result in kinase inhibition. This peptide also inhibits an active phospho-Cdk2-cyclin A complex, with a similar potency. Direct competition experiments have shown that this inhibitory peptide does not compete with Nck5a or cyclin A for Cdk5 or Cdk2, respectively. Steady state kinetic analysis has indicated that the alphaN peptide acts as a non-competitive inhibitor of Cdk5. Nck5a complex with respect to the peptide substrate. To understand the molecular basis of kinase inhibition by the peptide, we determined the structure of the peptide in solution by circular dichroism and two-dimensional 1H NMR spectroscopy. The peptide adopts an amphipathic alpha-helical structure from residues Ser149 to Arg162 which can be further stabilized by the helix-stabilizing solvent trifluoroethanol. The hydrophobic face of the helix is likely to be the kinase binding surface.  (+info)

We report the isolation of UME3, a C‐type cyclin that is required for the full repression of several early meiotic genes (e.g. SPO13) and SSA1, a member of the HSP70 superfamily. Similarly to other cyclin C family members, UME3 mRNA and protein levels remained unchanged throughout the mitotic cell cycle. However, under conditions that induce SSA1 or SPO13 transcription, we demonstrate that Ume3p is subjected to degradation. This destruction is required for normal meiotic gene induction, as a mutation that stabilizes Ume3p resulted in a 2‐fold reduction in SPO13 mRNA accumulation. These findings reveal the first observed regulation of a C‐type cyclin. Moreover, the destruction of Ume3p in response to heat shock or developmental cues represents a new set of regulatory signals by which any cyclin is controlled. We identified three cis‐acting domains (PEST‐rich, RXXL and the cyclin box) that contribute to the destruction of Ume3p during heat shock. In cultures exposed to heat shock, Ume3p ...
TY - JOUR. T1 - Identification of interaction partners and substrates of the cyclin A1-CDK2 complex. AU - Diederichs, Sven. AU - Bäumer, Nicole. AU - Ji, Ping. AU - Metzelder, Stephan K.. AU - Idos, Gregory E.. AU - Cauvet, Thomas. AU - Wang, Wenbing. AU - Möller, Maria. AU - Pierschalski, Sarah. AU - Gromoll, Jörg. AU - Schrader, Mark G.. AU - Koeffler, H. Phillip. AU - Berdel, Wolfgang E.. AU - Serve, Hubert. AU - Müller-Tidow, Carsten. PY - 2004/8/6. Y1 - 2004/8/6. N2 - The CDK2-associated cyclin A1 is essential for spermatogenesis and contributes to leukemogenesis. The detailed molecular functions of cyclin A1 remain unclear, since the molecular networks involving cyclin A1-CDK2 have not been elucidated. Here, we identified novel cyclin A1/CDK2 interaction partners in a yeast triple-hybrid approach. Several novel proteins (INCA1, KARCA1, and PROCA1) as well as the known proteins GPS2 (G-protein pathway suppressor 2), Ku70, receptor for activated protein kinase C1/guanine ...
Cyclin A2 activates the cyclin-dependent kinases Cdk1 and Cdk2 and is expressed at elevated levels from S phase until early mitosis. We found that mutant mice that cannot elevate cyclin A2 are chromosomally unstable and tumor-prone. Underlying the chromosomal instability is a failure to up-regulate the meiotic recombination 11 (Mre11) nuclease in S phase, which leads to impaired resolution of stalled replication forks, insufficient repair of double-stranded DNA breaks, and improper segregation of sister chromosomes. Unexpectedly, cyclin A2 controlled Mre11 abundance through a C-terminal RNA binding domain that selectively and directly binds Mre11 transcripts to mediate polysome loading and translation. These data reveal cyclin A2 as a mechanistically diverse regulator of DNA replication combining multifaceted kinase-dependent functions with a kinase-independent, RNA binding-dependent role that ensures adequate repair of common replication errors. ...
Cyclin F兔多克隆抗体(ab123601)可与人样本反应并经WB实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
マウス・モノクローナル抗体 ab38 交差種: Ms,Rat,Hu 適用: WB,IP,IHC-P,IHC-Fr,Flow Cyt…Cyclin A2抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody…
The cyclin E oncogene activates CDK2 to drive cells from G1 to S phase of the cell cycle to commence DNA replication. It coordinates essential cellular functions with the cell cycle including histone biogenesis, splicing, centrosome duplication and origin firing for DNA replication. The two E-cyclins, E1 and E2, are assumed to act interchangeably in these functions. However recent reports have identified unique functions for cyclins E1 and E2 in different tissues, and particularly in breast cancer. Cyclins E1 and E2 localise to distinct foci in breast cancer cells as well as co-localising within the cell. Both E-cyclins are found in complex with CDK2, at centrosomes and with the splicing machinery in nuclear speckles. However cyclin E2 uniquely co-localises with NPAT, the main activator of cell-cycle regulated histone transcription. Increased cyclin E2, but not cyclin E1, expression is associated with high expression of replication-dependent histones in breast cancers. The preferential localisation of
387453381 - EP 0863204 A4 20000119 - HUMAN CYCLIN I AND GENE ENCODING THE SAME - [origin: US6218115B1] This invention relates to a novel protein having a high degree of homology to the amino acid sequence of the so-called cyclin box which is characteristic of cyclins: they are herein referred to as human cyclin I or human cyclin I protein. Further, the invention relates to a gene encoding their amino acid sequences and the protein: the gene is referred to as gene encoding human cyclin I or human cyclin I gene. Also, the invention relates to expression vector into which the human cyclin I gene is incorporated as well as to a transformant into which the vector is introduced. Still further, the invention relates to a recombinant protein obtained by growing the transformant. In addition, the invention relates to a novel neuron-marking method using an anitisense nucleotide of the gene as probe. Furthermore, the invention relates to method for screening cancer cell using the human cyclin I gene.
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 in several malignancies and is associated with high proliferation, aberrant expression of other cell cycle regulators and chromosomal instability in vitro. To explore potential associations between cyclin E deregulation and inactivation of the p53 tumor suppressor gene in human breast cancer, we investigated the immunohistochemical expression of cyclin E in paraffin embedded breast cancers from 270 women with known p53 status by cDNA based sequencing of the p53 gene. The breast cancers were divided into three subgroups according to the percentage of cyclin E-positive cells. One hundred and seventy-one patients (63%) had low cyclin E, 72 (27%) medium and 27 (10%) had high cyclin E content. Fifty-six percent (15/27) of the breast cancers with high cyclin E had p53 gene mutations, compared with 14% (24/171) of those with low cyclin E content (P , 0.0001). In p53 mutated ...
Breast cancer is one of the most common malignancies in women. Due to early detection and the use of screening programs approximately 60% of all new cases lack lymph node involvement. Today, a substantial proportion of these women will be offered adjuvant systemic chemotherapy. However, better proliferation markers are needed to predict patient outcome and to avoid overtreatment. Cyclin A, cyclin E and Ki-67 are all markers for proliferation and involved in the regulation of the cell cycle. Overexpression has been associated with disease recurrence in several studies, but the results have not been consistent. However, none of these studies has investigated aberrant expression of cyclin E (the expression of cyclin E during phases of the cell cycle other than late G1 and early S-phase). Studies have shown that aberrant cyclin E might provide additional prognostic information compared to cyclin E alone.. The aims of this thesis were investigate the prognostic value of cyclin A, cyclin E and ...
MEF, a recently identified member of the E74 family of ETS-related transcription factors, is a strong transcriptional activator of cytokine gene expression. Using a green fluorescent protein gene reporter plasmid regulated by an MEF-responsive promot
The mammalian A-type cyclin family consists of two members, cyclin A1 (encoded by Ccna1) and cyclin A2 (encoded by Ccna2). Cyclin A2 promotes both G1/S and G2/M transitions, and targeted deletion of Ccna2 in mouse is embryonic lethal. Cyclin A1 is expressed in mice exclusively in the germ cell lineage and is expressed in humans at highest levels in the testis and certain myeloid leukemia cells. To investigate the role of cyclin A1 and possible redundancy among the cyclins in vivo, mice bearing a null mutation of Ccna1 were generated. Ccna1-/- males are sterile due to a block of spermatogenesis before the first meiotic division, whereas females are normal. Meiosis arrest in Ccna1-/- males is associated with increased germ cell apoptosis, desynapsis abnormalities and reduction of Cdc2 kinase activation at the end of meiotic prophase. Cyclin A1 is therefore essential for spermatocyte passage into the first meiotic division in male mice, a function that cannot be complemented by the concurrently ...
CBT for CCNA contains CCNA network simulator and exam simulator for CCNA. The features include 300+ questions in exam simulator with support to various question types, Detailed lab manual and more than 100 labs provided in network simulator. Practice Test Features: *Learn mode - In this mode one can see the Flash cards, and correct/wrong answers. *Exam mode - Here the candidate will be presented with a scenario that is close to the actual exam environment * 300+ highly ...
CCNA1 (cyclin A1), Authors: Immacolata Vocca, Gianmarco Muzi, Francesca Pentimalli, Antonio Giordano. Published in: Atlas Genet Cytogenet Oncol Haematol.
CCNE1 / Cyclin E1 Protein LS-G97233 is a Recombinant Human CCNE1 / Cyclin E1 produced in Baculovirus Met 1-Ala 410 with His tag(s). It is low in endotoxin; Less than 1.0 EU/µg protein (determined by LAL method).
An Intron-Retaining Splice Variant of Human Cyclin A2, Expressed in Adult Differentiated Tissues, Induces a G1-S Cell Cycle Arrest In Vitro. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
References for Abcams Recombinant Human Cyclin E1 protein (ab119719). Please let us know if you have used this product in your publication
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Whereas many components regulating the progression from S phase through G2 phase into mitosis have been identified, the mechanism by which these components control this critical cell cycle progression is still not fully elucidated. Cyclin A/Cdk2 has
Amino acids M1 - K726 (end) of human Cyclin T1. Residue M232 of the fusion protein is equivalent to M11 of the native enzyme. The GST tag is located at residues 1 - 220 ...
TY - JOUR. T1 - Altered p27Kip1 phosphorylation, localization, and function in human epithelial cells resistant to transforming growth factor β-mediated G1 arrest. AU - Ciarallo, Sandra. AU - Subramaniam, Venkateswaran. AU - Hung, Wesley. AU - Lee, Jin Hwa. AU - Kotchetkov, Rouslan. AU - Sandhu, Charanjit. AU - Milic, Andrea. AU - Slingerland, Joyce M. PY - 2002/5/6. Y1 - 2002/5/6. N2 - p27Kip1 is an important effector of G1 arrest by transforming growth factor β(TGF-β). Investigations in a human mammary epithelial cell (HMEC) model, including cells that are sensitive (184s) and resistant (184A1L5R) to G1 arrest by TGF-β, revealed aberrant p27 regulation in the resistant cells. Cyclin El-cyclin-dependent kinase 2 (cdk2) and cyclin A-cdk2 activities were increased, and p27-associated kinase activity was detected in 184A1L5R cells. p27 from 184A1L5R cells was localized to both nucleus and cytoplasm, showed an altered profile of phosphoisoforms, and had a reduced ability to bind and inhibit ...
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Cyclin T1 Antibody 20992-1-AP has been identified with WB, ELISA. 20992-1-AP detected 87 kDa band in K-562 cells with 1:200-1:1000 dilution...
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HIV replication in macrophages contributes to the latent viral reservoirs, which are considered the main barrier to HIV eradication. Few cellular factors that facilitate HIV replication in latently infected cells are known. We previously identified cyclin L2 as a critical factor required by HIV-1 and found that depletion of cyclin L2 attenuates HIV-1 replication in macrophages. Here we demonstrate that cyclin L2 promotes HIV-1 replication through interactions with the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Cyclin L2 and DYRK1A were colocalized in the nucleus and were found together in immunoprecipitation experiments. Knockdown or inhibition of DYRK1A increased HIV-1 replication in macrophages, while depletion of cyclin L2 decreased HIV-1 replication. Furthermore, depletion of DYRK1A increased expression levels of cyclin L2. DYRK1A is a proline-directed kinase that phosphorylates cyclin L2 at serine residues. Mutations of cyclin L2 at serine residues preceding ...
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 ...
FIG.9. Effects of UV stimulation on cyclin D1 and p52. (A) UV treatment down regulates cyclin D1 protein levels. U-2 OS cells were treated with 40-J/m2 UV radiation for the indicated times. Whole-cell lysates were prepared and immunoblotted for cyclin D1 and a β-actin control as indicated. (B) UV treatment inhibits the cyclin D1 promoter in a manner dependent upon the proximal κB element. One and a half micrograms of each of the cyclin D1 (−66) and cyclin D1 (−66 mut) luciferase reporter plasmids were transfected into U-2 OS cells. Cells were treated with 40-J/m2 UV radiation for 6 h as indicated. Results are expressed as change in activation or repression (n-fold) relative to levels seen in the relevant untreated cell controls. luc, luciferase. (C) UV treatment induces Ser-15 phosphorylated endogenous p53 and down regulates Bcl-3 levels. U-2 OS cells were treated with 40-J/m2 UV radiation for the indicated times. Nuclear protein extracts were prepared and immunoblotted for p53, ...
Looking for online definition of Cyclin F in the Medical Dictionary? Cyclin F explanation free. What is Cyclin F? Meaning of Cyclin F medical term. What does Cyclin F mean?
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.. ...
Genome doubling is an underlying cause of cancer cell aneuploidy and genomic instability, but few drivers have been identified for this process. Due to their physiological roles in the genome reduplication of normal cells, we hypothesised that the oncogenes cyclins E1 and E2 may be drivers of genome doubling in cancer. We show that both cyclin E1 (CCNE1) and cyclin E2 (CCNE2) mRNA are significantly associated with high genome ploidy in breast cancers. By live cell imaging and flow cytometry, we show that cyclin E2 overexpression promotes aberrant mitosis without causing mitotic slippage, and it increases ploidy with negative feedback on the replication licensing protein, Cdt1. We demonstrate that cyclin E2 localises with core preRC (pre-replication complex) proteins (MCM2, MCM7) on the chromatin of cancer cells. Low CCNE2 is associated with improved overall survival in breast cancers, and we demonstrate that low cyclin E2 protects from excess genome rereplication. This occurs regardless of p53 status,
Our experiments demonstrate the existence of a complex containing both cyclin E and several components of the U2 snRNP in vivo, in particular SAP 155, SAP 145, and SAP 114. We were able to detect the association between both cyclin E and SAP 155, as well as cdk2 and SAP 155, through either of the components in cellular lysates. The cyclin E-SAP 155 association can also be shown in the yeast two-hybrid system and can be reconstituted in vitro by using recombinant components. Furthermore, we found that cyclin E-specific antibodies were able to precipitate U1 and U2 snRNAs, as well as the pre-mRNA substrate from preassembled spliceosomes.. We find that one component of U2 snRNP, SAP 155, serves as an excellent substrate for cyclin E-cdk2 both in the U2/E/k2 complex precipitated from cells and as a recombinant protein in vitro. Phosphorylation of SAP 155 in the U2/E/k2 complex can be inhibited by preincubation of these complexes with p21, a known cyclin-kinase inhibitor. Taken together, these data ...
Cyclin A2 (encoded by CCNA2) is responsible for activating the cyclin-dependent kinases CDK1 and CDK2 to induce S-phase chromosome duplication and initiate mitosis. As both underexpression and overexpression of cyclin A2 have been linked to poor outcome in tumors, the role of cyclin A2 in tumor progression is unclear. Because complete loss of cyclin A2 is embryonically lethal, Kanakkanthara and colleagues developed a hypomorphic Ccna2 allele (Ccna2H) with reduced expression of cyclin A2 to better understand its role in tumorigenesis. Ccna2−/H mice had a marked reduction in cyclin A2 protein in tissues with a high mitotic index but relatively normal levels in tissues with less actively dividing cells. Ccna2−/H mice were more susceptible to spontaneous and carcinogen-induced tumors than Ccna2+/+ mice, indicating that cyclin A2 insufficiency promotes malignant transformation. Mouse embryonic fibroblasts (MEF) from Ccna2−/H mice exhibited increased aneuploidy due to chromosome segregation ...
TY - JOUR. T1 - Systematic determination of human cyclin dependent kinase (CDK)-9 interactome identifies novel functions in RNA splicing mediated by the DEAD Box (DDX)-5/17 RNA helicases. AU - Yang, Jun. AU - Zhao, Yingxin. AU - Kalita, Mridul. AU - Li, Xueling. AU - Jamaluddin, Mohammad. AU - Tian, Bing. AU - Edeh, Chukwudi B.. AU - Wiktorowicz, John E.. AU - Kudlicki, Andrzej. AU - Brasier, Allan R.. PY - 2015/10/1. Y1 - 2015/10/1. N2 - Inducible transcriptional elongation is a rapid, stereotypic mechanism for activating immediate early immune defense genes by the epithelium in response to viral pathogens. Here, the recruitment of a multifunctional complex containing the cyclin dependent kinase 9 (CDK9) triggers the process of transcriptional elongation activating resting RNA polymerase engaged with innate immune response (IIR) genes. To identify additional functional activity of the CDK9 complex, we conducted immunoprecipitation (IP) enrichment-stable isotope labeling LC-MS/MS of the CDK9 ...
The smooth progression of the eukaryotic cell cycle relies on the periodic activation of members of a family of cell cycle kinases by regulatory proteins called cyclins. Outside of the cell cycle, cyclin homologs play important roles in regulating the assembly of transcription complexes; distant structural relatives of the conserved cyclin core or box can also function as general transcription factors (like TFIIB) or survive embedded in the chain of the tumor suppressor, retinoblastoma protein. The present work attempts the prediction of the canonical secondary, supersecondary, and tertiary fold of the minimal cyclin box domain using a combination of techniques that make use of the evolutionary information captured in a multiple alignment of homolog sequences. A tandem set of closely packed, helical modules are predicted to form the cyclin box domain.
In humans, there are two A-type cyclins - an embryonic-specific cyclin A1 and a somatic cyclin A2. Cyclin A1 is only expressed in meiosis and very early embryos, whereas cyclin A2 is present in proliferating somatic cells
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 ...
2494 Cyclin I (CCNI) is a member of the recently described inhibitory class of cyclin proteins. The other members of this class, cyclins G1 and G2, have been implicated in the induction of cell cycle arrest. Cyclin I is widely expressed in terminally differentiated tissues, but its function remains to be determined. We previously identified cyclin I as antigenic in a mouse model of ovarian cancer. Here, we examined expression of the human cyclin I gene in normal tissues, in tumor cell lines, and in primary human ovarian tumors. By Northern blot analysis, cyclin I was expressed at moderate to high levels in all normal tissues examined, including normal ovary. In contrast, cyclin I mRNA was dramatically reduced in nine of twenty-five ovarian tumor samples examined. These studies were confirmed and extended using quantitative real-time PCR analysis. More than half of the tumors evaluated had very low levels of cyclin I mRNA compared to the expression levels in normal ovarian tissue and other normal ...
Data Availability StatementData are contained inside the paper. analysis from the transcriptional activity for ATF3, Wnt or NF-B. siRNA for ATF3 or p65 was employed for the knockdown of ATF3 and p65. Outcomes TC-HW decreased the cell viability in individual colorectal cancers cells. TC-HW reduced cyclin D1 proteins level through cyclin D1 degradation via GSK3-reliant threonine-286 (T286) phosphorylation of cyclin D1, indicating that cyclin D1 degradation might donate to TC-HW-mediated loss of cyclin D1 protein level. TC-HW downregulated the appearance of cyclin D1 mRNA level and Rabbit polyclonal to AREB6 inhibited Wnt activation through the downregulation of -catenin and TCF4 manifestation, indicating that inhibition of cyclin D1 transcription may also result in TC-HW-mediated decrease of cyclin D1 protein level. In addition, TC-HW was observed to induce apoptosis through ROS-dependent DNA damage. TC-HW-induced ROS improved NF-B and ATF3 activation, and inhibition of NF-B and ATF3 activation ...
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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
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Although most efforts to develop antagonists of CDK function have focused on identifying and optimizing ATP-competitive CDK inhibitors, a number of studies have been published in which new, creative strategies have been used. Most of these approaches focus on CDK2 inhibition. This is in part due to the fact that X-ray crystal structures of CDK2 and the cyclin A/CDK2 complex have been available longer than similar data for other CDK and cyclin/CDK complexes. A crystal structure of cyclin A/CDK2 in complex with ATP and a substrate peptide (Brown et al., 1999) (Fig. 3A) shows ATP bound in a cleft formed on one side by the GEGTYG nucleotide-binding motif (red- and blue-colored residues). The peptide substrate is bound in a cleft adjacent to the ATP binding site and in close apposition to ATP. Interestingly, binding of the endogenous CDK inhibitor p27 to cyclin A/CDK2 causes large-scale structural changes to the cyclin A/CDK2 complex (Fig. 3B) (Russo et al., 1996). p27 inserts itself into the ATP ...
Cyclin T2 antibody LS-C342834 is an unconjugated mouse monoclonal antibody to human Cyclin T2 (CCNT2 ). Validated for DB and WB.
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
Plasmid pIS1 Cyclin D2 short UTR from Dr. David Bartels lab contains the insert Cyclin D2 short UTR and is published in Cell. 2009 Aug 21. 138(4):673-84. This plasmid is available through Addgene.
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Amino acids S11 - H267 (end residue is R580) of human Cyclin K. Residue S232 of the fusion protein is equivalent to S11 of the native enzyme. The GST tag is located at residues 1 - 220 ...
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CNTD2 - CNTD2 (untagged)-Human cyclin N-terminal domain containing 2 (CNTD2), transcript variant 2 available for purchase from OriGene - Your Gene Company.
1W60: Structural and Biochemical Studies of Human Proliferating Cell Nuclear Antigen Complexes Provide a Rationale for Cyclin Association and Inhibitor Design
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 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/ ...
Different classes of cyclins are up- and down-regulated at different parts of the cell cycle. Measurement of the cyclins from ... For example, a peak of cyclin E protein would indicate the G1/S transition, a cyclin A peak would indicate late G2 phase, and a ... Cyclins are proteins that control progression through the cell cycle by activating cyclin-dependent kinases. Destruction of a ... This can actually be used to destroy phase-specific cyclins beyond just G2 - for instance, destruction of cyclin D1 mRNA by ...
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 ...
Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ...
... cyclin E, cyclin A and cyclin B1, each in relation to DNA content Concurrent measurement of DNA content and of incorporation of ... Darzynkiewicz Z, Gong JP, Juan G, Ardelt B, Traganos F (1996). "Cytometry of cyclin proteins". Cytometry. 25 (1): 1-13. doi: ... cell cycle compartments are also recognized by multiparameter analysis that includes measurement of expression of cyclin D1, ...
... contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein may play an important role in ... 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. CS1 maint: discouraged parameter (link) v t e. ...
... activates cyclin dependent kinases by removing phosphate from residues in the Cdk active site. In turn, the ... Cyclin "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. cdc25+ ... May 1991). "Dephosphorylation and activation of a p34cdc2/cyclin B complex in vitro by human CDC25 protein". Nature. 351 (6323 ... By removing inhibitory phosphate residues from target cyclin-dependent kinases (Cdks), Cdc25 proteins control entry into and ...
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 LD, ... Cyclin-dependent kinase 1 (CDK1), the cyclin-dependent kinase subunit. It uses ATP to phosphorylate specific serine and ...
... , a cyclin protein. This disambiguation page lists articles associated with the title CYCB. If an internal link led you ...
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 ... "Entrez Gene: CCNL2 cyclin L2". Human CCNL2 genome location and CCNL2 gene details page in the UCSC Genome Browser. Maruyama K, ...
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". 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". 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 (20 December 2017). "Activators of cyclin- ...
Also involved in the phosphorylation and regulation of the RPB1 CTD is cyclin T1 (CCNT1). Cyclin T1 tightly associates and ... CDK8 and cyclin C (CCNC) are components of the RNA polymerase II holoenzyme that phosphorylate the carboxy-terminal domain (CTD ... 2002). "A kinase-cyclin pair in the RNA polymerase II holoenzyme". Nature. 374 (6518): 193-6. doi:10.1038/374193a0. PMID ... TFIIH is a large protein complex that contains among others the CDK7/cyclin H kinase complex and a DNA helicase. TFIIH has ...
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 ...
... 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 ...
Jain SK, Bharate SB, Vishwakarma RA (2012). "Cyclin-dependent kinase inhibition by flavoalkaloids". Mini Rev Med Chem. 12 (7): ... Bose P, Simmons GL, Grant S (2013). "Cyclin-dependent kinase inhibitor therapy for hematologic malignancies". Expert Opin ...
... has been shown to interact with: CDC45-related protein and CDC6, Cell division cycle 7-related protein kinase, Cyclin- ... Laman H, Peters G, Jones N (Dec 2001). "Cyclin-mediated export of human Orc1". Experimental Cell Research. 271 (2): 230-7. doi: ... "Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase". ... "Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase". ...
Cyclin D-bound cdks 4 and 6 are activated by cdk-activating kinase and drive the cell towards the restriction point. Cyclin D, ... Sustained mitogen signaling promotes cell cycle entry largely through regulation of the G1 cyclins (cyclin D1-3) and their ... including the major G1 cyclin, cyclin D1. Myc also regulates expression of a wide variety of pro-proliferative and pro-growth ... The defining biochemical feature of the restriction point is the activation of G1/S- and S-phase cyclin-CDK complexes, which in ...
Hunter, Tony; Pines, Jonathan (1994). "Cyclins and cancer II: Cyclin D and CDK inhibitors come of age". Cell. 79 (4): 573-582. ... "Human cyclin A is adenovirus E1A-associated protein p60 and behaves differently from cyclin B". Nature. 346 (6286): 760-763. ... Hunter, Tony; Pines, Jonathon (1991). "Cyclins and cancer". Cell. 66 (6): 1071-1074. doi:10.1016/0092-8674(91)90028-W. PMID ...
This discovery was essential to the subsequent cloning of Xenopus cyclins and kept the Hunt lab at the forefront of cyclin ... Hunter, Tony; Pines, Jonathon (1994). "Cyclins and cancer II: Cyclin D and CDK inhibitors come of age". Cell. 79 (4): 573-582. ... Subsequently he cloned and characterised the first human cyclins with Tony Hunter. This was crucial to recognising that cyclins ... and identified the first link between cyclins and oncoproteins by showing that cyclin A bound to adenovirus E1A, thus linking ...
It has also been shown that Cdk2 complexes with both cyclin A and cyclin E and this complex is critical for centrosome ... by cyclin-dependent kinase 2-cyclin E and its role in centrosome duplication". The Journal of Biological Chemistry. 276 (24): ... "CDK2 cyclin dependent kinase 2 [Homo sapiens (human)]". Gene - NCBI. Retrieved 1 December 2019. Hinchcliffe EH, Li C, Thompson ... This link between the cell cycle and the centrosome cycle is mediated by cyclin-dependent kinase 2 (Cdk2). Cdk2 is a protein ...
... cyclin-dependent kinase 12 is a protein kinase that in humans is encoded by the CDK12 gene. This enzyme is a member of ... "Entrez Gene: CDK12 cyclin-dependent kinase 12". Human CDK12 genome location and CDK12 gene details page in the UCSC Genome ... cyclin-dependent kinase protein family. GRCh38: Ensembl release 89: ENSG00000167258 - Ensembl, May 2017 GRCm38: Ensembl release ...
"Targets of the cyclin-dependent kinase Cdk1". Nature. 425 (6960): 859-864. Bibcode:2003Natur.425..859U. doi:10.1038/nature02062 ...
The degradation of cyclins is the key step that governs the exit from mitosis and progress into the next cell cycle. Cyclins ... The cyclins are removed via a ubiquitin-mediated proteolytic pathway. Caspases are an important group of proteases involved in ... Cyclins are a group of proteins that activate kinases involved in cell division. ... Glotzer M, Murray AW, Kirschner MW (1991). "Cyclin is degraded by the ubiquitin pathway". Nature. 349 (6305): 132-8. Bibcode: ...
"Cyclin G1 and cyclin G2 comprise a new family of cyclins with contrasting tissue-specific and cell cycle-regulated expression ... Cyclin-G1 is a protein that in humans is encoded by the CCNG1 gene. The eukaryotic cell cycle is governed by cyclin-dependent ... "Entrez Gene: CCNG1 cyclin G1". Zhao L, Samuels T, Winckler S, Korgaonkar C, Tompkins V, Horne MC, Quelle DE (Jan 2003). "Cyclin ... The protein encoded by this gene is a member of the cyclin family and contains the cyclin box. The encoded protein lacks the ...
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. ...
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 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 ...
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.
... é regulado pelos cyclins, um tipo de proteína que liga e activa quinase do dependente do cyclin (CDKs). Crédito de imagem: ... Para cada fase, há um grupo correspondente de cyclins: Cyclins G1, cyclins de G1/S, cyclins de S e cyclins de M, cada um com ... A função dos cyclins no ciclo de pilha. Cyclins não tem nenhuma função enzimático do seus próprios, e liga-a pelo contrário a ... Descoberta de Cyclins. Cyclins foi descoberto pela caça de Timothy, pelo Leland H. Hartwell e pela enfermeira de Paul M, que ...
... Charles Yang cyang at 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 ...
Protein levels of cyclin B1 and cdc2 for each selected population are shown in Fig. 4B. Levels of cyclin B1 protein in cyclin ... Cyclin A regulates the initiation and maintenance of DNA synthesis whereas B cyclins control mitosis (32, 33). Cyclin B mRNA ... Cyclin B1/cdc2 kinase activity is shown in Fig. 4C. Cyclin B1 rescues the p53-dependent drop in cdc2 kinase activity in Ts- ... Cyclin B1 Expression Rescues p53-Mediated G2 Arrest.. To determine whether the decrease in cyclin B1 mRNA was the primary ...
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. ...
... 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 balczonr at 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 ...
Cyclin-dependent kinase inhibitor 2B regulates efferocytosis and atherosclerosis. Yoko Kojima, Kelly Downing, Ramendra Kundu, ... We have previously demonstrated that loss of one candidate gene at this locus, cyclin-dependent kinase inhibitor 2B (Cdkn2b), ... See the related article at Cyclin-dependent kinase inhibitor 2B regulates efferocytosis and atherosclerosis. ...
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 ...
These thresholds are sequentially triggered as cyclin increases, yielding reliable order and timing. In many biological ... We conclude that mitotic events are regulated by discrete cyclin-CDK thresholds. ... Rising cyclin-CDK levels order cell cycle events PLoS One. 2011;6(6):e20788. doi: 10.1371/journal.pone.0020788. Epub 2011 Jun ... Background: Diverse mitotic events can be triggered in the correct order and time by a single cyclin-CDK. A single regulator ...
... Cancer Chemother Biol Response Modif. 2002;20:169-96. ...
Download the full report: 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 ...
Rabbit polyclonal Cyclin T1 antibody validated for WB, IP, ELISA, IHC and tested in Human, Mouse and Rat. Referenced in 10 ... Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation ... Anti-Cyclin T1 antibody (ab2098) at 1/10000 dilution + HeLa (Human epithelial carcinoma cell line) Whole Cell Lysate at 10 µg. ... ab2098 (2µg/ml) staining Cyclin T1 in human lymph node using an automated system (DAKO Autostainer Plus). Using this protocol ...
Compare Anti-Cyclin K Antibody Products from leading suppliers on Biocompare. View specifications, prices, citations, reviews, ... Anti-Cyclin K Antibody Products. Anti-Cyclin K antibodies are available from several suppliers. In humans, this protein is ...
  • Cyclins, when bound with the dependent kinases , such as the p34 / cdc2 / cdk1 protein, form the maturation-promoting factor . (
  • Cyclins function as regulators of CDK kinases. (
  • They act in conjunction with cyclin-dependent protein kinases, which are proteins that phosphorylate other proteins. (
  • What are Cyclin-Dependent Kinases? (
  • Cyclin-dependent kinases are a type of serine/threonine kinase which are activated by cyclins to drive the progress of the cell cycle. (
  • Cyclin dependent kinases are present at constant levels throughout the cell cycle, but are only active in the presence of cyclins. (
  • Eukaryotic cell cycle progression is regulated by cyclin dependent protein kinases (CDKs) whose activity is regulated by association with cyclins and by reversible phosphorylation. (
  • p53 inhibits G 1 /S transition in cells exposed to DNA-damaging agents by causing accumulation of p21 CIP1/WAF1 ( 6 , 15 ), a protein that binds to and inactivates the cyclin-dependent kinases necessary for initiating DNA synthesis ( 16 ). (
  • These findings suggest that at least one of the biochemical steps required for mitosis, activation of cyclin A-dependent protein kinases, is also an important event during apoptosis. (
  • Not only were both of the known cell cycle transitions, from G 1 to S phase and G2 to M phase, found to be dependent on these protein kinases, but the reg- ulatory assumption intrinsic to cyclin-dependent kinases, a stable inactive catalytic subunit (the Cdk) and an unstable requisite positive regulatory activating subunit (the cyclin), led to a simple model for cell cycle control. (
  • Targeting cyclins and cyclin-dependent kinases in cancer: lessons from mice, hopes for therapeutic applications in human. (
  • This is known as the cell cycle and cyclins and their partners, cyclin-dependant kinases, are its master control proteins. (
  • NEW YORK - Cyclins and cyclin-dependent kinases like CDK7 and CDK12 are recurrently altered genetically in a range of cancer types, providing insight into potential treatment strategies, according to a new study. (
  • Cyclin-dependent kinases (CDKs) typically bind cyclins and regulate a number of downstream proteins that are key components of cell division and transcription. (
  • Cyclin A1 is a member of the highly conserved cyclin family whose members are able to control the progression of cells through the cell cycle by activating cyclin-dependent kinases (CDKs). (
  • 1991). Cyclin A family members are characterized by a typical periodicity in protein abundance through the cell division cycle functioning as activating subunits of enzymatic complexes, together with cyclin-dependent kinases (CDKs) (Lapenna and Giordano, 2009). (
  • 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. (
  • D-type cyclins associate with partner cyclin-dependent kinases, CDK4 and CDK6, and promote phosphorylation and subsequent inactivation of the retinoblastoma tumor suppressor gene product, RB and RB-related proteins. (
  • They also interact with cyclin-dependent kinases to control cell cycle progression in plants. (
  • This cyclin binds both CDK2 and CDC2 kinases, which give two distinct kinase activities, one appearing in S phase, the other in G2, and thus regulate separate functions in cell cycle. (
  • Cyclins are characterized by a dramatic periodicity in protein abundance throughout the cell cycle and function as regulators of CDK kinases. (
  • CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. (
  • Cyclins are regulatory subunits of the cyclin-dependent kinases (cdks) and they control transition at different specific phases of the cell cycle. (
  • The key cell-cycle regulator Cdc2 belongs to a family of cyclin-dependent kinases in higher eukaryotes. (
  • A dominant-negative Cdc2 mutant arrested cells at the G2 to M phase transition, whereas mutants of the cyclin-dependent kinases Cdk2 and Cdk3 caused a G1 block. (
  • The induction of cyclin D1 can also be mediated by a target of p53, the p21 (WAF1/CIP1) inhibitor of cyclin-dependent kinases. (
  • Cyclins bind to and regulate the activity of the Cyclin dependent protein kinases (CDKs). (
  • Strikingly, RNA polymerase II (RNAPII) is itself a substrate for two protein kinases-the cyclin-dependent kinases Cdk7 and Cdk9-that are activated by hypertrophic cues. (
  • Cyclins are eukaryotic proteins that play an active role in controlling nuclear cell division cycles [ ( PUBMED:12910258 ) ], and regulate cyclin dependent kinases (CDKs). (
  • Cyclins, together with the p34 (cdc2) or cdk2 kinases, form the Maturation Promoting Factor (MPF). (
  • For example, in all eukaryotes mitosis (M phase) is initiated by high levels of cyclin B, which combines with a protein kinase to form the mitosis-promoting factor (MPF). (
  • To identify the mechanism by which p53 regulates G 2 , we have derived a human ovarian cell that undergoes p53-dependent G 2 arrest at 32°C. We have found that p53 prevents G 2 /M transition by decreasing intracellular levels of cyclin B1 protein and attenuating the activity of the cyclin B1 promoter. (
  • To study G 2 regulation by p53, we have established a human cell line, Ts-SKOV3, that stably expresses a temperature-sensitive p53 allele and undergoes G 2 arrest at 32°C. Using this cell line we have found that p53 arrests cell cycle in G 2 by lowering intracellular levels of cyclin B1, a protein absolutely required for mitotic initiation. (
  • The more aggressive basal-like subtype of breast cancers, however, exhibited lower levels of cyclin D1 and Dicer, which would in turn globally reduce the level of mature miRNA. (
  • The study involved cancer samples from 264 Taiwanese male oral cavity squamous cell carcinoma (OSCC) patients, and the results showed that increased levels of cyclin D1 were linked with later stage cancer and increased chance of the tumor spreading, as well as a reduced chance of survival. (
  • More research is needed, but assessing levels of cyclin D1 at diagnosis could help to personalize treatment. (
  • Of the seven patients who had a recurrence, six had high levels of cyclin E activity. (
  • RESULTS- Mice treated with exendin-4 showed increased β-cell proliferation, elevated islet protein levels of cyclin A2 with unchanged D-type cyclins, elevated PDX-1 and Skp2 levels, and reduced p27 levels. (
  • Human prostate carcinoma cell lines frequently express elevated levels of cyclin D1 protein, although the gene is not amplified in these cells ( 18 ). (
  • Cyclin A is also produced, which binds to CDK2 and stimulates DNA replication. (
  • Analysis of residues that are conserved throughout the A, B, and E cyclins identifies two exposed clusters of residues, one of which has recently been shown to be involved in the association with human CDK2. (
  • Comparison of the structure of the unbound cyclin with the structure of cyclin A complexed with CDK2 reveals that cyclin A does not undergo any significant conformational changes on complex formation. (
  • Where examined, both Cdc2 and Cdk2, the catalytic subunits known to associate with cyclin A, were activated. (
  • However, their research also showed that treating breast cancer cells with a cyclin-dependent kinase 2 (CDK2) inhibitor can reverse letrozole resistance. (
  • After confirming that the LMW forms of cyclin E suppress the anti-proliferative effects of letrozole, the researchers examined whether a CDK2 inhibitor could reverse the drug resistance in the unresponsive breast cancer cells. (
  • We challenged the aromatase-overexpressing cells with either the wild-type or the low forms of cyclin E and then treated them with the CDK2 inhibitor roscovitine," Keyomarsi said. (
  • Cyclin A1 belongs to the A-type cyclin family of proteins originally identified as 60 kDa polypeptides associated to CDK2 and interacting with viral proteins (Giordano et al. (
  • 2005). Human cyclin A1 interacts with CDK2 in vitro and in vivo (Yang et al. (
  • 2001). Moreover the cyclin A1-CDK2 complex regulates DNA double-strand break repair following radiation damage (Müller-Tidow et al. (
  • 2004) by competing with CDK2-cyclin A2 for the binding to Ku70, a pivotal player in the non-homologous end-joining double strand break repair pathway, and inhibiting apoptosis through modulating RB functions in leukemia cells (Ji et al. (
  • CDK2 is a catalytic subunit of the cyclin-dependent protein kinase complex, and is essential for cell cycle G1⁄S phase transition. (
  • Cdk2 and cyclin E, long thought to be essential, are largely dispensable. (
  • Cyclin E forms a complex with and functions as a regulatory subunit of CDK2, whose activity is required for cell cycle G1/S transition. (
  • Cyclin A binds to S phase Cdk2 and is required for the cell to progress through the S phase. (
  • Cyclin A/ Cdk2 is inhibited by the complex p21CIP. (
  • Cyclin E binds to the G1 phase Cdk2, which is required for the transition from G1 to S phase of the cell cycle that determines cell division. (
  • The Cyclin E/CDK2 complex phosphorylates p27Kip1, tagging it for degradation, thus promoting expression of Cyclin A, allowing progression to S phase. (
  • Hbo1 is a cyclin E/CDK2 substrate that enriches breast cancer stem-like cells. (
  • Cyclin is a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes . (
  • For example, the amino-terminal regions of S and M cyclins contain short destruction-box motifs that target these proteins for proteolysis in mitosis. (
  • cyclin Any of a family of proteins that help control the various phases of the cell cycle . (
  • Once bound to a cyclin they act to phosphorylate many target proteins on serine or threonine amino acid residues. (
  • Each interacts with a different cyclin at a different phase, stimulating various target proteins and ensuring that vital stages of each phase are carried out before a cell moves onto the next phase. (
  • I wonder if the cytoplasmic staining we are getting is real or whether the methacarn is modifying other cytoplasmic proteins (like other cyclins, maybe) to mimic the characteristics of cyclin E. If you have any ideas, please let me know. (
  • Threading analysis shows that the cyclin-box fold is consistent with the sequences of the transcription factor TFIIB and other functionally related proteins. (
  • Cyclin is a family of proteins that controls the progression of a cell through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes or group of enzymes required for synthesis of cell cycle. (
  • Molecular analyses revealed that cells lacking cyclin E fail to normally incorporate MCM proteins into DNA replication origins during G(0)-->S progression. (
  • The work supports the idea that cancer-causing proteins like cyclin D1 may drive cancer progression in part via miRNA biogenesis. (
  • Dr Bill Wickstead, who along with his master's student Alexander Douglass characterised cyclin-like genes across Apicomplexa, said: "Cyclins are a really diverse class of proteins comprising many different types in different organisms. (
  • Cyclin E is one of the proteins that regulates the cell cycle, influencing how rapidly a cell passes through the four phases and divides. (
  • This cyclin was found to bind to important cell cycle regulators, such as Rb family proteins, transcription factor E2F-1, and the p21 family proteins. (
  • After incubation with cell lysates, both phospho and nonphospho cyclin D1 proteins are captured by the coated antibody. (
  • Transcription of these particular cyclins is proposed to monitor the growth factor signal and the encoded proteins participate in G1 progression. (
  • Additionally we are shipping Cyclin H Antibodies (129) and Cyclin H Proteins (15) and many more products for this protein. (
  • Additionally we are shipping Cyclin K Kits (12) and Cyclin K Proteins (7) and many more products for this protein. (
  • Proteolytically processed forms of cyclin E proteins, which are specifically generated in tumors that overexpress cyclin E proteins. (
  • There are 14939 Cyclin_C domains in 14900 proteins in SMART's nrdb database. (
  • Taxonomic distribution of proteins containing Cyclin_C domain. (
  • The complete taxonomic breakdown of all proteins with Cyclin_C domain is also avaliable . (
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing Cyclin_C domain in the selected taxonomic class. (
  • Cyclins themselves have no enzymatic activity but have binding sites for some substrates and target the Cdks to specific subcellular locations. (
  • These cyclins oscillate, increasing and decreasing at different stages, binding to CDKs and driving the cell cycle forward. (
  • In addition to cyclin levels, this provides and additional way to control the activity of CDKs. (
  • Cyclins also determine the subcellular location and substrate specificity of CDKs. (
  • O ciclo de pilha é regulado pelos cyclins, um tipo de proteína que liga e activa quinase do dependente do cyclin (CDKs). (
  • Cyclins não tem nenhuma função enzimático do seus próprios, e liga-a pelo contrário a CDKs para ativá-los. (
  • More than 10 years ago, the discovery of cyclin-dependent ki- nases (Cdks) ushered in a new era in the understanding of cell proliferation and its control. (
  • For example, although Cdks appear to be highly conserved phylogenetically, cyclins are much less so. (
  • In a new study, researchers from the University of Pennsylvania now analyzed copy number gains and losses as well as other alterations affecting cyclins and CDKs in more than 10,000 tumors. (
  • As they reported in Cell Reports on Tuesday , the researchers found that cell cycle-related cyclins and CDKs were often amplified in tumors, but that copy number losses, especially affecting CDK7 and CDK12, also occurred. (
  • They identified more than two dozen CDKs and cyclins that were recurrently altered. (
  • Cell cycle-linked CDKs and cyclins were often amplified in cancers, but transcription-linked CDKs and cyclins tended to experience copy number losses. (
  • Our genomic analysis provided an additional rationale for the clinical development of targeting transcriptional CDKs/cyclins, especially for CDK7-targeted therapy," Zhang and his colleagues wrote. (
  • The temporal expression of cyclins is tightly regulated and subsequently plays a critical role in controlling the enzymatic activity of cdks. (
  • Multiple cyclins activate CDKs in all eukaryotes, but it is unclear whether multiple cyclins are really required for cell cycle progression. (
  • Dowejko, Bauer, Bauer, Müller-Richter, Reichert: The human HECA interacts with cyclins and CDKs to antagonize Wnt-mediated proliferation and chemoresistance of head and neck cancer cells. (
  • There are currently no images for Cyclin C Antibody (NB120-2950). (
  • Western Blot: Cyclin A1 Antibody [NBP1-02902] - Cyclin A1 western with U2OS cells. (
  • Immunohistochemistry-Paraffin: Cyclin A1 Antibody [NBP1-02902] - Human testis after heat-induced antigen retrieval. (
  • The absorbance readings at 450 nm are shown in the top figure, while the corresponding western blot using Cyclin D1 Antibody #2922, is shown in the bottom figure. (
  • A Cyclin D1 Rabbit Antibody has been coated onto the microwells. (
  • Following extensive washing, Cyclin D1 Mouse Detection Antibody is added to detect the captured cyclin D1 protein. (
  • The following product was used in this experiment: Cyclin E1 Monoclonal Antibody (4H7) from Thermo Fisher Scientific, catalog # BSM-52048R. (
  • The following product was used in this experiment: Cyclin B1 Polyclonal Antibody from Thermo Fisher Scientific, catalog # 55004-1-AP. (
  • WB analysis of extracts from various cell lines using Cyclin H antibody. (
  • ICC/IF analysis of HeLa cells using Cyclin H antibody (green) and DAPI (blue). (
  • Cyclin B1 antibody detects Cyclin B1 protein at cytoplasm on mouse ovary by immunohistochemical analysis. (
  • But, with Cyclin E antibodies, we get cytoplasmic staining rather than nuclear staining which is mentioned in all the literature I have read. (
  • Anti-Cyclin K antibodies are available from several suppliers. (
  • Your search returned 117 Cyclin K Antibodies across 20 suppliers. (
  • Your search returned 1 cyclin Q Antibodies across 1 supplier. (
  • Anti-Cyclin Antibodies are ideal for investigators involved in Cell Signaling, cell biology and Signal Transduction research. (
  • On are 17 Cyclin H (CCNH) ELISA Kits from 4 different suppliers available. (
  • Tumor samples were immunostained for cyclin B using commercial antibodies. (
  • This cyclin shows the highest similarity with cyclin G. The transcript of this gene was found to be expressed constantly during cell cycle progression. (
  • Cyclin I is involved in the regulation of cell cycle progression. (
  • We have previously demonstrated that loss of one candidate gene at this locus, cyclin-dependent kinase inhibitor 2B (Cdkn2b), in mice promotes vascular SMC apoptosis and aneurysm progression. (
  • The role of cyclins in controlling G1 progression in mammalian cells was tested by construction of fibroblasts that constitutively overexpress human cyclin E. This was found to shorten the duration of G1, decrease cell size, and diminish the serum requirement for the transition from G1 to S phase. (
  • 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. (
  • Cyclin A1 primarily functions in the meiotic cell cycle, but it also seems to contribute to G1/S cell cycle progression in somatic cells (Ji et al. (
  • Taken together, our results demonstrate that cyclin D2 has a critical role in cell cycle progression and the tumorigenicity of GSCs. (
  • D-type cyclins are known to have critical roles in cell cycle progression. (
  • 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. (
  • Cyclin E is an important regulator of cell cycle progression. (
  • Destruction of Cyclin B1 is required for cell cycle progression. (
  • Cyclin E deregulation impairs mitotic progression through premature activation of Cdc25C. (
  • We hypothesized that intrapituitary cyclin E signaling regulates corticotroph tumor POMC transcription independently of cell cycle progression. (
  • A gene on chromosome 9q34.1 that encodes a cyclin-dependent kinase, which regulates cell cycle progression. (
  • The cyclin D1 oncogene encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the Rb protein and promotes progression through G 1 to S phase of the cell cycle. (
  • However, the relationship between cyclin D1 expression and prostate tumor progression has yet to be clearly characterized. (
  • Cyclin D2, a positive regulator of G1 progression, shows a unique localization within radial glial (RG) cells (i.e., the neural progenitor in the developing neocortex). (
  • Using antisense RNA, Dr. Pestell's group was the first to show that cyclin D1 drives mammary tumor growth in vivo. (
  • Here we show that cyclin D2 is the cyclin that is predominantly expressed in GSCs and suppression of its expression by RNA interference causes G1 arrest in vitro and growth retardation of GSCs xenografted into immunocompromised mice in vivo . (
  • In conclusion, the findings of this study show that cyclin D1 has separate roles, and proliferation is driven by different mechanisms in ER positive and negative breast cancers. (
  • Western blotting was used to measure cyclin-dependent kinase (CDK) inhibitors p21 and p27 that arrest cell cycle. (
  • p27(KIP1) is a member of the CIP1/KIP1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. (
  • Some of the non-biological drugs, known as Cyclin-dependent kinase (CDK) inhibitors, are currently being tested for use in cancer treatment. (
  • Altered prostatic epithelial proliferation and apoptosis, prostatic development and serum testosterone in mice lacking cyclin-dependent kinase inhibitors," Biology of Reproduction 73(5): 951-958. (
  • in opposition to this idea, it has been argued that cyclins might target the activated CDK to particular substrates or inhibitors. (
  • AIMS: Cyclin-dependent kinase inhibitors (CDKIs) play a critical role in negatively regulating the proliferation of cardiomyocytes, although their role in cardiac differentiation remains largely undetermined. (
  • Pituitary cyclin E/E2F1 signaling is a previously unappreciated molecular mechanism underlying neuroendocrine regulation of the hypothalamic-pituitary-adrenal axis, providing a subcellular therapeutic target for small molecule cyclin-dependent kinase 2 inhibitors of pituitary ACTH-dependent hypercortisolism, ie, Cushing disease. (
  • In thisreview, we focus our attention on cyclin-cyclin-dependent kinase complexes,cyclin kinase inhibitors, genes of the retinoblastoma family, p53 and N-Myc, and we aim to summarize the latest evidence indicating their involvement in thecontrol of the cell cycle and induction of differentiation in different celltypes of the peripheral and central nervous systems. (
  • Cell changes in the cell cycle like the assembly of mitotic spindles and alignment of sister-chromatids along the spindles are induced by M cyclin- Cdk complexes. (
  • It depicts the many complexes of cyclin and Cdk (cyclin/Cdk) as fulfilling unique and essential steps that dictate the sequential order of cell cycle events. (
  • These cyclin/cdk complexes are essential for passage through specific stages in the cell cycle. (
  • Cyclin B1 complexes with p34 (cdc2) to form the maturation-promoting factor (MPF). (
  • SETD1A and cyclin K complexes may represent a therapeutic opportunity for acute myeloid leukemia and, potentially, for other cancers. (
  • Cyclin K-containing kinase complexes maintain self-renewal in murine embryonic stem cells. (
  • It is known that the cell cycle and cell proliferation are regulated by the sequential activation of cyclin-dependent kinase/cyclin complexes. (
  • This cyclin and its kinase partner are components of TFIIH, as well as RNA polymerase II protein complexes. (
  • Cyclin B1 is the regulatory subunit of the cdc2 kinase and is a protein required for mitotic initiation. (
  • This protein forms a complex with and is regulated by its regulatory subunit cyclin T or cyclin K. HIV-1 Tat protein was found to interact with CDK9 and cyclin T, which suggested a possible involvement of this protein in AIDS. (
  • Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to productive elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). (
  • In budding yeast, commitment occurs when the catalytic subunit of a protein kinase, encoded by the CDC28 gene (the homolog of the fission yeast cdc2+ gene), binds to a positively acting regulatory subunit, a cyclin. (
  • Cyclin D1 forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G 1 /S transition. (
  • Retinoblastoma protein (Rb) usually functions to inhibit the transcription factor E2F, however, when cyclin-D-CDK4 phosphorylates the Rb protein, this relinquishes inhibition of E2F and leads to the production of genes required for entering the S phase. (
  • These genes include cyclin E, which binds to CDK4, driving the cell cycle into the S phase. (
  • For their analysis, the researchers determined the somatic copy number alterations, mutations, and transcript fusions affecting 21 CDK genes and 26 cyclin genes within The Cancer Genome Atlas. (
  • 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). (
  • 5 Three D-type cyclins, cyclin D1, D2 and D3, are encoded by distinct genes, but show significant amino-acid similarity. (
  • Our genome-wide analysis identified 52 expressed cyclin genes in tomato. (
  • Quantitative real-time polymerase chain reaction analysis indicates that the expression patterns of tomato cyclin genes were significantly different in vegetative and reproductive stages. (
  • 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. (
  • 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. (
  • The treatment of quiescent cells with growth factors results in the transcriptional activation of the D-type cyclin genes during G1. (
  • 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. (
  • It is normally activated by cyclin C and is required for transcription elongation of the serum response genes (immediate early genes [IEGs]) FOS, EGR1, and cJUN. (
  • RV-cyclin does not control CDK8 specificity but instead enhances CDK8's effects on regulated genes, an important distinction for its use to delineate natural CDK8 targets. (
  • The Saccharomyces cerevisiae C-type cyclin and its cyclin-dependent kinase (Cdk8p) repress the transcription of several stress response genes. (
  • A cyclin forms a complex with Cdk, which begins to activate but the complete activation requires phosphorylation, as well. (
  • Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. (
  • The cyclin H / cdk7 (show CDK7 ELISA Kits )/ Mat1 (show MAT1A ELISA Kits ) kinase activity is regulated by CK2 (show CSNK2A1 ELISA Kits ) phosphorylation of cyclin H . (
  • Investigation of the pUL97-cyclin T1 interaction in an ATP consumption assay strongly suggested phosphorylation of pUL97 by the CDK9/cyclin T1 complex in a substrate concentration-dependent manner. (
  • RV-cyclin does not increase activating phosphorylation events in the mitogen-activated protein kinase pathway and does not inhibit decay of IEG mRNAs. (
  • The levels of S cyclins remain high, not only throughout S phase, but through G2 and early mitosis as well to promote early events in mitosis. (
  • M cyclin concentrations rise as the cell begins to enter mitosis and the concentrations peak at metaphase. (
  • The destruction of M cyclins during metaphase and anaphase, after the Spindle Assembly Checkpoint is satisfied, causes the exit of mitosis and cytokinesis. (
  • Finally, cyclin B binds to CDK-1 to drive the cycle forward into M phase, stimulating mitosis. (
  • Cyclin B1 is a regulatory protein involved in mitosis. (
  • The D and E type cyclins regulate the passage of G1, while cyclin B is a critical regulator of mitosis. (
  • Cyclin B1 is not ubiquitinated during G2/M phase, resulting in its steady accumulation during G2 phase, followed by abrupt APC dependent destruction at the end of mitosis. (
  • The cyclin concentration increases during the cycle until halfway to the mitosis stage, when it drops to zero. (
  • Cyclin may act as a molecular switch that activates mitosis when its concentration reaches a certain point. (
  • Low molecular weight cyclin E overexpression shortens mitosis, leading to chromosome missegregation and centrosome amplification. (
  • During RG division, Cyclin D2 protein is asymmetrically distributed to two daughter cells following mitosis. (
  • There are two main groups of cyclins, G1/S cyclins, which are essential for the control of the cell cycle at the G1/S (start) transition, and G2/M cyclins, which are essential for the control of the cell cycle at the G2/M (mitosis) transition. (
  • G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). (
  • Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase 4 or Cell Division Protein Kinase 9 or Serine/Threonine Protein Kinase PITALR or CDK9 or EC or EC - Cyclin-dependent kinase 9 (CDK9) is a cyclin-dependent kinase associated with P-TEFb. (
  • Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase 4 or Cell Division Protein Kinase 9 or Serine/Threonine Protein Kinase PITALR or CDK9 or EC or EC pipeline Target constitutes close to 26 molecules. (
  • It also reviews key players involved in Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase 4 or Cell Division Protein Kinase 9 or Serine/Threonine Protein Kinase PITALR or CDK9 or EC or EC targeted therapeutics development with respective active and dormant or discontinued projects. (
  • Cyclin Dependent Kinase 7 (39 kDa Protein Kinase or CDK Activating Kinase 1 or Cell Division Protein Kinase 7 or TFIIH Basal Transcription Factor Complex Kinase Subunit or Serine/Threonine Protein Kinase 1 or CDK7 or EC or EC - Cell division protein kinase 7 is an enzyme that in humans is encoded by the CDK7 gene. (
  • Cyclin Dependent Kinase 7 (39 kDa Protein Kinase or CDK Activating Kinase 1 or Cell Division Protein Kinase 7 or TFIIH Basal Transcription Factor Complex Kinase Subunit or Serine/Threonine Protein Kinase 1 or CDK7 or EC or EC pipeline Target constitutes close to 11 molecules. (
  • In prior work, they showed that cyclin D1 regulates the non coding genome, and that the non-coding genome, in turn, regulates expression of cyclin D1. (
  • In the current study, the group sought to investigate the mechanism by which cyclin D1 regulates the biogenesis of non coding miRNA. (
  • Finally, two results suggest that cyclin C regulates programmed cell death independently of its function as a transcriptional repressor. (
  • Unlike other cyclins that positively regulate the cell cycle, cyclin G2 (CCNG2) regulates cell proliferation as a tumor suppressor gene. (
  • Kaposi sarcoma herpesvirus ( KSHV ) encodes a D-type cyclin (ORF72) that binds CDK6 and is likely to contribute to KSHV-related cancers [9] . (
  • Initially, a mitogenic stimulus leads to the upregulation of cyclin D gene expression, which binds to CDK4. (
  • It binds to cyclin-dependent kinase 8 (CDK8) and enhances its kinase activity. (
  • In tumor cells, cyclin E is converted to low-molecular weight forms, an event that does not occur in normal cells. (
  • A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. (
  • Cyclin E and E2F transcription factor 1 (E2F1) small interfering RNA (siRNA) transfection was performed in murine corticotroph tumor AtT20 cells to elucidate mechanisms for drug action. (
  • R-roscovitine inhibits human pituitary corticotroph tumor ACTH by targeting the cyclin E/E2F1 pathway. (
  • These data indicated that the tumor-promoting activity of cyclin D1 may be tissue specific. (
  • This supports results from earlier studies that suggest that cyclin D1 could be used as a prognostic biomarker. (
  • We suggest that cyclin B might be a potent prognostic factor in this low-risk patient group. (
  • This cyclin and its kinase partner CDK9 were found to be subunits of the transcription elongation factor p-TEFb. (
  • Cyclin T2 has been shown to interact with CDK9 and Retinoblastoma protein. (
  • Cyclin K interacts with CDK12 and CDK13 but not CDK9 in cells, and is required to maintain self-renewal in ES cells. (
  • Cyclin K inhibits HIV-1 gene expression and replication by interfering with cyclin-dependent kinase 9 (CDK9)-cyclin T1 interaction in Nef-dependent manner. (
  • These results reveal an unexpectedly direct role for CDK9-cyclin K in checkpoint pathways that maintain genome integrity in response to replication stress. (
  • P-TEFb containing cyclin K and Cdk9 can activate transcription via RNA. (
  • The primary mechanism of CDK activation is binding to corresponding cyclins, including cyclin T1, which is the usual regulatory cofactor of CDK9. (
  • HIV-1 Tat protein interacts with CDK9 and cyclin T, suggesting CDK9 may have a role in AIDS. (
  • Study TPI-ALV-201 is examining the efficiency of alvocidib, an investigational inhibitor of cyclin-dependent kinase 9 (CDK9), in combination with the authorized agents cytarabine and mitoxantrone in relapsed/refractory AML patients whose leukemia depends on MCL-1. (
  • Biopharmaceutical company Probiodrug AG revealed on Friday the transfer of its experimental cyclin-dependent kinase 9 (CDK9) inhibitor programme to AstraZeneca (LSE:AZN)(NYSE:AZN) for an undisclosed amount. (
  • Cyclin specificity: how many wheels do you need on a unicycle? (
  • The sensitivity and specificity of cyclin B was 65% and 92%, respectively. (
  • The p-TEFb complex containing this cyclin was reported to interact with, and act as a negative regulator of human immunodeficiency virus type 1 (HIV-1) Tat protein. (
  • A single regulator could confer order and timing on multiple events if later events require higher cyclin-CDK than earlier events, so that gradually rising cyclin-CDK levels can sequentially trigger responsive events: the "quantitative model" of ordering. (
  • They did this by expressing the cell-cycle regulator, a protein called cyclin A2. (
  • These results define both a new function for SNIP1 and identify a previously unrecognized regulator of the cell cycle and cyclin D1 expression. (
  • Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. (
  • Second, the human cyclin C, which does not repress transcription in yeast, does regulate ROS sensitivity. (
  • Cyclins positively regulate cell proliferation to a large extent. (
  • 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 are critically required for proliferation of all cell types. (
  • Here, we demonstrate that E type cyclins are largely dispensable for mouse development. (
  • These findings define a molecular function for E type cyclins in cell cycle reentry and reveal a differential requirement for cyclin E in normal versus oncogenic proliferation. (
  • b ) The mRNA levels of D-type cyclins in undifferentiated (stem) or differentiated (diff) GB1-3 and 5 cells were evaluated by quantitative RT-PCR. (
  • CBP-S436A islets exhibited elevated cyclin A2, reduced p27, and no changes in D-type cyclins, PDX-1, or Skp2. (
  • C-, H- and J18 types only contain a cyclin-C domain, and U-type cyclins contain another potential cyclin domain. (
  • 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. (
  • We show here that accumulation of the wild-type p53 protein in either human or murine cells markedly increases expression of cyclin D1. (
  • The expression of cyclin H and CDK7 (show CDK7 ELISA Kits ) protein in proliferating hemangiomas was significantly higher than that in involuting hemangiomas and normal skin tissues. (
  • We found that low-risk node negative patients with high expression of cylin B had a significantly worse outcome than patients with low expression of cyclin B. Cyclin B could separate patients with poor survival from those with good survival with 80% accuracy. (
  • By the way, the name cyclin, which I coined, was really a joke, it's because I liked cycling so much at the time, but they did come and go in the cell. (
  • Expression of human cyclins through the cell cycle . (
  • Cyclins were originally named because their concentration varies in a cyclical fashion during the cell cycle. (
  • Note that the cyclins are now classified according to their conserved cyclin box structure, and not all these cyclins alter in level through the cell cycle. (
  • [5] ) The oscillations of the cyclins, namely fluctuations in cyclin gene expression and destruction by the ubiquitin mediated proteasome pathway, induce oscillations in Cdk activity to drive the cell cycle. (
  • 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. (
  • This division is useful when talking about most cell cycles, but it is not universal as some cyclins have different functions or timing in different cell types. (
  • The cyclins also promote other activities to progress the cell cycle, such as centrosome duplication in vertebrates or spindle pole body in yeast. (
  • G1 cyclins do not behave like the other cyclins, in that the concentrations increase gradually (with no oscillation), throughout the cell cycle based on cell growth and the external growth-regulatory signals. (
  • The presence of G cyclins coordinate cell growth with the entry to a new cell cycle. (
  • [6] Expression of cyclins detected immunocytochemically in individual cells in relation to cellular DNA content (cell cycle phase), [7] or in relation to initiation and termination of DNA replication during S-phase, can be measured by flow cytometry . (
  • The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. (
  • CDC28 was identified in Saccharomyces cerevisiae , which bound to cyclins and drove the cell through the various transitions of the cell cycle. (
  • Knockdown of Cyclin I induced cell cycle arrest at S/G2/M phases. (
  • Cyclins were originally discovered by R. Timothy Hunt in 1982 while studying the cell cycle of sea urchins. (
  • There are several different cyclins that are active in different parts of the cell cycle and that cause the Cdk to phosphorylate different substrates. (
  • Modulation of cyclin accumulation, and thereby Cdk activation, was proposed to be the overarching principle governing the passage through cell cycle phases. (
  • However, endoreplication of trophoblast giant cells and megakaryocytes is severely impaired in the absence of cyclin E. Cyclin E-deficient cells proliferate actively under conditions of continuous cell cycling but are unable to reenter the cell cycle from the quiescent G(0) state. (
  • In addition to its role in regulating the cell cycle, cyclin D1 induces Dicer and thereby promotes the maturation of miRNA," says lead researcher Richard Pestell, M.D., Ph.D., Director of the Kimmel Cancer Center at Thomas Jefferson University and Chair of the Department of Cancer Biology. (
  • Real-time RT-PCR demonstrated that the expression of the cell cycle-driving molecule, cyclin-dependent kinase 4 (Cdk4), in HCC was significantly reduced by the treatments with vitamin K2, K3 and K5. (
  • Cyclin A1 transfected 293T cell line lysate. (
  • Dr Magali Roques, who is the lead author said: "This first functional study of cyclin in the malaria parasite and its consequences in parasite development within pathogen-carrying mosquitoes will definitely further our understanding of parasite cell division, which I hope will lead to the elimination of this disease in the future. (
  • The research, focused on the role of cyclin, one of the most important protein molecules needed for cell division. (
  • However, until now, very little was known about cyclins in the malaria parasite, Plasmodium, which undergoes atypical types of cell cycle during its development both in the human host where the disease is manifested and in the vector mosquito which transmits the disease. (
  • 6-Gingerol induces cell-cycle G1-phase arrest through AKT-GSK 3β-cyclin D1 pathway in renal-cell carcinoma. (
  • Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. (
  • It is unique in its control at two major transitions of the cell cycle and is the only cyclin that is completely silenced after birth in mice, rats and humans. (
  • Cyclin A1 is also expressed in several myeloid leukemia cell lines and various other tumour types (Yang et al. (
  • 2004). Cyclin A1 has an important role in the development of acute myeloid leukemia (AML): its localization in normal hematopoietic cells is nuclear, whereas in leukemic cells from AML patients and cell lines, it is predominantly cytoplasmic (Ekberg et al. (
  • Male knockout mice lacking cyclin A1 are infertile owing to a cell cycle arrest before the first meiotic division (Liu et al. (
  • Here, we discuss the phenotypes of these and other cyclin/Cdk mutants in genetically tractable metazoa (mouse, fly, and nematode) and explore possible reasons behind similarities and differences among experimental systems and cell types. (
  • RESEARCH DESIGN AND METHODS- Changes in islet protein levels of cyclins and of two critical cell cycle regulators cyclin kinase inhibitor p27 and S-phase kinase-associated protein 2 (Skp2) were assessed in mice treated with exendin-4 and in a mouse model with specific upregulation of nuclear cAMP signaling exhibiting increased β-cell proliferation (CBP-S436A mouse). (
  • CONCLUSIONS- Cyclin A2 is required for β-cell proliferation, exendin-4 stimulates cyclin A2 expression via the cAMP pathway, and exendin-4 stimulation of cAMP requires PDX-1. (
  • Cyclins play important roles in cell division and cell expansion. (
  • The cyclin encoded by this gene was shown to be expressed in testis and brain, as well as in several leukemic cell lines, and is thought to primarily function in the control of the germline meiotic cell cycle. (
  • In addition to its role in regulating the cell cycle cyclin D1 induc. (
  • However, this kit has a low detection level for cyclin D1 in some cell lines, such as HeLa, Mv 1 Lu or NIH/3T3. (
  • Cyclin D1 is unsuitable for minimal residual disease monitoring in bone marrow of patients with mantle cell lymphoma. (
  • Overexpression of cyclin D1 results in dysregulated CDK (zeige CDK4 Proteine ) activity, rapid cell growth under conditions of restricted mitogenic signaling, bypass of key cellular checkpoints, and ultimately, neoplastic growth. (
  • in its absence, cyclins D2 and D3 are also not expressed, preventing hematopoietic cell division and differentiation at its earliest stage. (
  • Induction of mammary gland hyperplasia and carcinomas in transgenic mice expressing human cyclin E. Mol Cell Biol. (
  • Expression of cell cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients. (
  • Cyclin-dependent kinase (CDK) activity is essential for eukaryotic cell cycle events. (
  • Experimental data has suggested that cyclin D1 and E mediate cell proliferation by different mechanisms in estrogen receptor (ER) positive and negative breast cancer. (
  • Cyclin B1 is overexpressed in various cancers, including breast, prostate, and non-small cell lung cancer. (
  • that cyclin K may be a novel molecular link between germ cell development, cancer development and embryonic stem cell maintenance. (
  • P16-INK4a interacts strongly with cyclin-dependent kinase 4 and cyclin-dependent kinase 6 and inhibits their ability to interact with cyclins D. P16-INK4a induces cell cycle arrest at G1 and G2/M checkpoints, blocking them from phosphorylating RB1 and preventing exit from G1 phase of the cell cycle. (
  • The distribution patterns of pUL97 and cyclin T1 were independent of HCMV strain and host cell type. (
  • Here we show that constitutive expression of RV-cyclin in the HCT116 colon cancer cell line significantly increases the level of IEG expression in response to serum stimulation. (
  • These findings demonstrate a new role for the Slt2p MAP kinase cascade in protecting the cell from programmed cell death through cyclin C destruction. (
  • Several prostate cancer cell lines and a subset of primary prostate cancer samples have increased cyclin D1 protein expression. (
  • The data showed that overexpression of cyclin D1 in the initiated BPH-1 cell line increased cell proliferation rate but did not elicit tumorigenicity in vivo . (
  • Studies have shown that mouse prostatic normal and Rb −/− epithelial cells have elevated cyclin D1 expression as they enter the cell cycle ( 18 ). (
  • Cyclin D2 accumulates at the very basal tip of the RG cell (i.e., the basal endfoot) via a unique cis -regulatory sequence found in the 3′ untranslated region (3′UTR) of its mRNA. (
  • The daughter cell that inherits Cyclin D2 mRNA maintains its self-renewal capability, while its sibling undergoes differentiation. (
  • Aim We evaluated epidermal cell turnover and thickness, as well as the expression of cyclins D1, B and A in psoriatic skin before and after therapy with cyclosporin. (
  • Methods Epidermal thickness, mitotic and apoptotic indices (MI, AI), as well as the percentages of epidermal cell nuclei positive for Ki-67 and cyclins D1, B and A were calculated. (
  • Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (
  • The ability of p53 to control mitotic initiation by regulating intracellular cyclin B1 levels suggests that the cyclin B-dependent G 2 checkpoint has a role in preventing neoplastic transformation. (
  • For all of the apoptosis-inducing agents tested, the appearance of condensed chromatin was accompanied by 2- to 7-fold increases in cyclin A-associated histone H1 kinase activity, levels approximating the mitotic value. (
  • Diverse mitotic events can be triggered in the correct order and time by a single cyclin-CDK. (
  • We titrated the budding yeast mitotic cyclin Clb2 within its endogenous expression range to a stable, fixed level and measured time to occurrence of three mitotic events: growth depolarization, spindle formation, and spindle elongation, as a function of fixed Clb2 level. (
  • We conclude that mitotic events are regulated by discrete cyclin-CDK thresholds. (
  • G2/mitotic-specific cyclin-B2, HsT17299, cyclin B2. (
  • The structural results indicate a role for the cyclin-box fold both as a template for the cyclin family and as a generalised adaptor molecule in the regulation of transcription. (
  • Although cyclin D1 had no effect on STAT3 DNA binding, cyclin D1 did bind to the transcriptional activation domain of STAT3, suggesting a mechanism whereby STAT3-dependent transcription could be immediately attenuated. (
  • 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. (
  • PDX-1 knockdown reduced exendin-4-stimulated cAMP synthesis and cyclin A2 transcription. (
  • Human cdk8-cyclin C might be functionally associated with the mammalian transcription apparatus, perhaps involved in relaying growth-regulatory signals. (
  • I have been defining the cis -acting elements and trans -acting factors that control transcription of the human cyclin D3 gene in T-cells. (
  • The minimal cyclin D3 promoter sequence was identified as a region 173bp upstream of the transcription initiation site. (
  • The protein encoded by CCNK is a member of the transcription cyclin family. (
  • Retroviral cyclin controls cyclin-dependent kinase 8-mediated transcription elongation and reinitiation. (
  • Previous work showed that the retroviral cyclin (RV-cyclin), encoded by WDSV, has separable cyclin box and transcription activation domains. (
  • Quantitative reverse transcription-PCR (RT-PCR) and nuclear run-on assays provide evidence that RV-cyclin does not alter the initiation of IEG transcription but does enhance the overall rate of transcription elongation and maintains transcription reinitiation. (
  • 1997). The cyclin A1 promoter does not possess a TATA box, whereas the region upstream of the transcriptional start site region contains four GC boxes, with multiple Sp1-binding sites important for the regulation of cyclin A1 expression (Müller et al. (
  • Cyclin H is implicated in the regulation of the transcriptional machinery during midblastula transition and is therefore an essential gene in early zebrafish larval development. (
  • Cyclin E-Mediated Human Proopiomelanocortin Regulation as a Therapeutic Target for Cushing Disease. (
  • Cyclin E and E2F1 exhibit reciprocal positive regulation in corticotroph tumors. (
  • Alvocidib is an investigational small molecule inhibitor of cyclin-dependent kinase 9 , a protein important to the regulation of Myc. (
  • Microarray analysis showed that the expression profiles between CAFs and NPF cyclin D1 cells were highly concordant including cyclin D1 up-regulation. (
  • However, all members of the cyclin family are similar in 100 amino acids that make up the cyclin box. (
  • Within the protein the cyclin box is a region of protein sequence homology that is common to all members of the cyclin family and is required for interaction with the CDK partner. (
  • In contrast to mammalian cells, these yeast cells had only one CDK which interacted with various cyclins. (
  • Mammalian cyclin A1 is primarily localized in the nuclei of spermatocytes in mouse and human (Liu et al. (
  • In mammalian somatic cells, cyclin A is required for S-phase and passage through G2-phase. (
  • Cyclin K is highly expressed in mammalian testes in a developmentally regulated manner. (
  • Here, we discuss our findings and the Cyclin D2 function in mammalian brain development and evolution. (
  • Cyclin-dependent kinase 6 (CDK6) bound to the inhibitor ribociclib (detail view). (
  • Verzenio is a cyclin-dependent kinase (CDK)4 & 6 inhibitor that will be available as 50, 100, 150 and 200 mg tablets. (
  • HOUSTON - Overexpression of low-molecular-weight (LMW-E) forms of the protein cyclin E renders the aromatase inhibitor letrozole ineffective among women with estrogen-receptor-positive (ER+) breast cancers, researchers from The University of Texas M. D. Anderson Cancer Center report in Clinical Cancer Research . (
  • The M. D. Anderson team hypothesized that ER+ breast cancer patients whose tumors express the LMW forms of cyclin E would be less responsive to treatment with an aromatase inhibitor. (
  • This arrest is characterized by accumulation of the cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) and of underphosphorylated forms of retinoblastoma protein. (
  • Cardiac differentiation in Xenopus requires the cyclin-dependent kinase inhibitor, p27Xic1. (
  • Belongs to the cdkn2 cyclin-dependent kinase inhibitor family. (
  • Cyclin-Dependent Kinase Inhibitor p21" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (
  • This graph shows the total number of publications written about "Cyclin-Dependent Kinase Inhibitor p21" by people in Harvard Catalyst Profiles by year, and whether "Cyclin-Dependent Kinase Inhibitor p21" was a major or minor topic of these publication. (
  • Below are the most recent publications written about "Cyclin-Dependent Kinase Inhibitor p21" by people in Profiles. (
  • Cyclin A2 overexpression in primary islets increased proliferation and reduced p27. (
  • In Min6 cells, cyclin A2 knockdown prevented exendin-4-stimulated proliferation. (
  • To test this hypotheses in large breast cancer material and to clarify the histopathological correlations of cyclin E and D1, especially the association with proliferation, we analyzed cyclin E and D1 immunohistochemical expression on breast tumour microarrays consisting of 1348 invasive breast cancers. (
  • The differences at each stage are due to a balance between the gene expression of each cyclin and the ubiquitin-proteasome system which breaks them down. (
  • Overexpression of cyclin D1 reduced STAT3-dependent gene expression in a dose-dependent manner. (
  • At the EGR1 gene locus, RV-cyclin increases and maintains RNA polymerase II (Pol II) occupancy after serum stimulation, in conjunction with increased and extended EGR1 gene expression. (
  • Donnellan R, Kleinschmidt I, Chetty R. Cyclin E immunoexpression in breast ductal carcinoma: pathologic correlations and prognostic implications. (
  • We wanted to examine cyclin B as a prognostic factor in low-risk breast cancer patients. (
  • The aim was to investigate whether R-roscovitine inhibits human ACTH in corticotroph tumors by targeting the cyclin-dependent kinase 2/cyclin E signaling pathway. (
  • A similar localization pattern of Cyclin D2 protein has been observed in the human fetal cortical primordium, suggesting a common mechanism of maintenance of neural progenitors that may be evolutionarily conserved across higher mammals such as primates. (
  • S cyclins bind to Cdk and the complex directly induces DNA replication. (
  • The Cdk- G1/S cyclin complex begins to induce the initial processes of DNA replication, primarily by arresting systems that prevent S phase Cdk activity in G1. (
  • Confocal immunofluorescence revealed partial colocalization of pUL97 with cyclin T1 in subnuclear compartments, most pronounced in viral replication centres. (
  • The mechanism behind this is that the low forms of cyclin E increase the activity of the cyclin E complex, and this complex is what mediates the negative effects. (
  • However, overexpression of cyclin D1 in normal prostate fibroblasts (NPF) that were subsequently recombined with BPH-1 did induce malignant transformation of the epithelial cells. (
  • Overexpression of cyclin D1 plays important roles in the development of human cancers, including breast, colon, and melanoma ( 11 , 13 - 17 ). (
  • Because the cyclin D1 gene has been implicated in a variety of other human cancers these findings may have broad implications for processing of non coding RNA in human tumorigenesis. (
  • Background: Cyclin D1 gene (CCND1) plays pivotal roles in the development of several human cancers, including breast cancer, functioning as an oncogene. (
  • A second prediction of the model is that increasing the rate of cyclin accumulation should globally advance timing of all events. (
  • Cyclins are generally very different from each other in primary structure, or amino acid sequence. (
  • Cyclins exhibit diverse sequences but all share homology over a region of approximately 100 amino acids, termed the cyclin box. (
  • My problem: I can't find the nucleotide and amino acid sequences for the Cyclin H gene (the human counterpart to CCL1) and its corresponding protein. (
  • It recognizes a protein of 54kDa, which is identified as cyclin A. Its epitope is located amino acids 144-148 of human Cyclin A2. (
  • The sequence domain of pUL97 responsible for the interaction with cyclin T1 was between amino acids 231-280. (
  • 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. (
  • Recombinant human Cyclin E1 protein, around 100-200aa. (
  • Recombinant protein encompassing a sequence within the center region of human Cyclin B1. (
  • We found that we could negate the growth inhibitory effects of letrozole with the low forms of cyclin E but not with the wild-type cyclin E," said Keyomarsi, the study's senior author. (
  • Of those, 100 expressed normal levels of wild-type cyclin E, and 28 overexpressed the low forms," Keyomarsi said. (
  • When we looked at recurrence, three of the hundred with wild-type cyclin E had experienced a recurrence compared to four of the twenty-eight with the low forms. (
  • Graf L, Webel R, Wagner S, Hamilton ST, Rawlinson WD, Sticht H, Marschall M. The Cyclin-Dependent Kinase Ortholog pUL97 of Human Cytomegalovirus Interacts with Cyclins. (
  • Exendin-4 stimulated cyclin A2 promoter activity via the cAMP-cAMP response element binding protein pathway. (
  • The human cyclin D3 gene has a TATA-less promoter and a single dominant initiation site. (
  • Transient transfections using CAT (chloramphenicol acetyltransferase) reporter constructs containing sequential deletions of the cyclin D3 promoter defined positively and negatively regulated regions. (
  • Cyclin K1 is the primary cyclin partner for CDK12/CrkRS and it is required for activation of CDK12/CrkRS to phosphorylate the C-terminal domain of RNA Pol II. (