A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.
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 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 broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.
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 cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.
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.
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 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.
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 widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.
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.
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.
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.
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.
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.
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.
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 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.
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 B subtype that colocalizes with GOLGI APPARATUS during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).
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 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 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.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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.
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.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
Cyclin-dependent kinase 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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
A cell line derived from cultured tumor cells.
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 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.
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.
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.
A quiescent state of cells during G1 PHASE.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
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 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.
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.
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.
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.
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 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.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Established cell cultures that have the potential to propagate indefinitely.
A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.
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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
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.
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.
Tumors or cancer of the human BREAST.
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 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.
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.
An aspect of protein kinase (EC in which serine residues in protamines and histones are phosphorylated in the presence of ATP.
The process by which a DNA molecule is duplicated.
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)
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.
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.
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.
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.
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.
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.
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 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.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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).
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.
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.
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.
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.
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.
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 enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
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.
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 biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Transport proteins that carry specific substances in the blood or across cell membranes.
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.
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 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.
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 family of structurally related proteins that were originally discovered for their role in cell-cycle regulation in CAENORHABDITIS ELEGANS. They play important roles in regulation of the CELL CYCLE and as components of UBIQUITIN-PROTEIN LIGASES.
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.
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.
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.
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 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.
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.
The phosphoric acid ester of threonine. Used as an identifier in the analysis of peptides, proteins, and enzymes.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
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.
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.
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 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.
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.
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 aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from http://www.atcc.org/)
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.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
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 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.
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.
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 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).
Elements of limited time intervals, contributing to particular results or situations.
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.
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).
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.
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.
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.
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.

The role of RBF in the introduction of G1 regulation during Drosophila embryogenesis. (1/1162)

The first appearance of G1 during Drosophila embryogenesis, at cell cycle 17, is accompanied by the down-regulation of E2F-dependent transcription. Mutant alleles of rbf were generated and analyzed to determine the role of RBF in this process. Embryos lacking both maternal and zygotic RBF products show constitutive expression of PCNA and RNR2, two E2F-regulated genes, indicating that RBF is required for their transcriptional repression. Despite the ubiquitous expression of E2F target genes, most epidermal cells enter G1 normally. Rather than pausing in G1 until the appropriate time for cell cycle progression, many of these cells enter an ectopic S-phase. These results indicate that the repression of E2F target genes by RBF is necessary for the maintenance but not the initiation of a G1 phase. The phenotype of RBF-deficient embryos suggests that rbf has a function that is complementary to the roles of dacapo and fizzy-related in the introduction of G1 during Drosophila embryogenesis.  (+info)

Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (2/1162)

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. (3/1162)

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)

Growth-inhibitory effect of cyclic GMP- and cyclic AMP-dependent vasodilators on rat vascular smooth muscle cells: effect on cell cycle and cyclin expression. (4/1162)

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)

Heparin inhibits proliferation of myometrial and leiomyomal smooth muscle cells through the induction of alpha-smooth muscle actin, calponin h1 and p27. (5/1162)

Mast cells are widely distributed in human tissues, including the human uterus. However, the function of mast cells in uterine smooth muscle has not been clearly established. Mast cells possess secretory granules containing such substances as heparin, serotonin, histamine and many cytokines. To help establish the role of mast cells in the human myometrium, the action of heparin was investigated using smooth muscle cells (SMC) from normal myometrium and from leiomyoma. The proliferation of cultured myometrial and leiomyomal SMC was inhibited by heparin treatment. Flow cytometric analysis showed that the population in the G1 phase of the cell cycle increased under heparin treatment. Western blotting analysis showed that markers of SMC differentiation such as alpha-smooth muscle actin (alpha-SMA), calponin h1 and cyclin-dependent kinase inhibitor p27 were induced by heparin, whereas cell-cycle-related gene products from the G1 phase of the cell cycle, such as cyclin E and cdk2, were not changed. Taken together, these results indicate that heparin inhibits the proliferation of myometrial and leiomyomal SMC through the induction of alpha-SMA, calponin h1 and p27. We suggest that heparin from mast cells may induce differentiation in uterine SMC and may influence tissue remodelling and reconstruction during physiological and pathophysiological events.  (+info)

Impact of 9-(2-phosphonylmethoxyethyl)adenine on (deoxy)ribonucleotide metabolism and nucleic acid synthesis in tumor cells. (6/1162)

Following exposure to 9-(2-phosphonylmethoxyethyl)adenine (an inhibitor of the cellular DNA polymerases alpha, delta and epsilon), human erythroleukemia K562, human T-lymphoid CEM and murine leukemia L1210 cells markedly accumulated in the S phase of the cell cycle. In contrast to DNA replication, RNA synthesis (transcription) and protein synthesis (mRNA translation) were not affected by 9-(2-phosphonylmethoxyethyl)-adenine. The ribonucleoside triphosphate pools were slightly elevated, while the intracellular levels of all four deoxyribonucleoside triphosphates were 1.5-4-fold increased in 9-(2-phosphonylmethoxyethyl)adenine-treated K562, CEM and L1210 cells. The effect of 9-(2-phosphonylmethoxyethyl)adenine on de novo (thymidylate synthase-mediated) and salvage (thymidine kinase-mediated) dTTP synthesis was investigated using radio-labelled nucleoside precursors. The amount of thymidylate synthase-derived dTTP in the acid soluble pool was 2-4-fold higher in PMEA-treated than in untreated K562 cells, which is in accord with the 3-4-fold expansion of the global dTTP level in the presence of 9-(2-phosphonylmethoxyethyl)adenine. Strikingly, 2-derived dTTP accumulated to a much higher extent (i.e. 16-40-fold) in the soluble dTTP pool upon 9-(2-phosphonylmethoxyethyl)adenine treatment. In keeping with this finding, a markedly increased thymidine kinase activity could be demonstrated in extracts of 9-(2-phosphonylmethoxyethyl)adenine-treated K562 cell cultures. Also, in the presence of 200 microM 9-(2-phosphonylmethoxyethyl)adenine, 14-fold less thymidylate synthase-derived but only 3-fold less thymidine kinase-derived dTTP was incorporated into the DNA of the K562 cells. These data show that thymidine incorporation may be inappropriate as a cell proliferation marker in the presence of DNA synthesis inhibitors such as 9-(2-phosphonylmethoxyethyl)adenine. Our findings indicate that 9-(2-phosphonylmethoxyethyl)adenine causes a peculiar pattern of (deoxy)ribonucleotide metabolism deregulation in drug-treated tumor cells, as a result of the metabolic block imposed by the drug on the S phase of the cell cycle.  (+info)

Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27(Kip1). (7/1162)

Proliferation and apoptosis are increased in many types of inflammatory diseases. A role for the cyclin kinase inhibitor p27(Kip1) (p27) in limiting proliferation has been shown. In this study, we show that p27(-/-) mesangial cells and fibroblasts have strikingly elevated rates of apoptosis, not proliferation, when deprived of growth factors. Apoptosis was rescued by restoration of p27 expression. Cyclin A-cyclin-dependent kinase 2 (CDK2) activity, but not cyclin E-CDK2 activity, was increased in serum-starved p27(-/-) cells, and decreasing CDK2 activity, either pharmacologically (Roscovitine) or by a dominant-negative mutant, inhibited apoptosis. Our results show that a new biological function for the CDK inhibitor p27 is protection of cells from apoptosis by constraining CDK2 activity. These results suggest that CDK inhibitors are necessary for coordinating the cell cycle and cell-death programs so that cell viability is maintained during exit from the cell cycle.  (+info)

Retardation of cell proliferation after expression of p202 accompanies an increase in p21(WAF1/CIP1). (8/1162)

p202 is an IFN-inducible, primarily nuclear, phosphoprotein (52-kDa) whose constitutive overexpression in transfected cells inhibits colony formation. To investigate the molecular mechanism(s) by which expression of p202 protein impairs colony formation, we established stable cell lines that inducibly express p202. Using this cell model, we demonstrate that the induced expression of p202 in asynchronous cultures of these cells was accompanied by: (a) an increase in steady-state levels of p21(WAF1/CIP1/SDI1) (p21) mRNA and protein; (b) a decrease in Cdk2 protein kinase activity; and (c) an increase in the functional form of retinoblastoma protein (pRb). Transient transfection of a p202-encoding plasmid in Saos-2 cells, which do not harbor a wild-type p53 protein, resulted in an increase in p21 protein, which indicated that p202 could regulate expression of p21 protein independent of p53 protein. Moreover, we demonstrate that expression of p202 in these cells increased cell doubling time without accumulation of cells in a particular phase of the cell cycle. Taken together, these results are consistent with the possibility that p202 protein contributes to the cell growth retardation activity of the IFNs, at least in part, by modulating p21 protein levels.  (+info)

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
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 ...
Aim: This study investigates the prognostic value of cyclin E in relation to tumour growth pattern by analysing stage II primary breast cancers from premenopausal women not subjected to any further adjuvant treatment. In addition, the value of cyclin E as a predictor of tamoxifen response was analysed, by comparing untreated and treated patients with oestrogen receptor positive tumours. Methods: Breast cancer samples, assembled in tissue microarrays, were immunohistochemically stained for cyclin E and evaluated regarding the presence of nuclear staining. The overall growth characteristics of each tumour were assessed using whole tissue sections. Results: Tumours displaying a pushing margin phenotype were strongly associated with high cyclin E levels, lymph node negative disease, a high histological grade, ER negativity, and exhibited a better prognosis compared to tumours with an infiltrative growth pattern. In the total cohort of non-treated patients (N=187), cyclin E was not associated with ...
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
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 ...
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,
The G1 cyclins, cyclin D1 and E, are rate limiting for progression through G1 phase of the cell cycle in breast epithelial cells and are oncogenic when expressed in the mammary epithelium of transgenic mice. These genes are frequently overexpressed in clinical breast cancer where overexpression appears to be associated with specific disease phenotypes, altered responsiveness to therapeutic intervention and patient survival. In order to investigate the functional correlates of cyclin D1 and cyclin E overexpression we employed a panel of normal, immortalized and neoplastic breast epithelial cell lines to examine the relationships between cyclin gene expression, cyclin-CDK complex formation and CDK activity. In agreement with earlier studies cyclin D1 and E expression varied over an approximately tenfold range among the 18 cell lines studied. There was no apparent relationship, however, between cyclin D1 expression and the in vitro activity of its major kinase partner, Cdk4, although MDA-MB-134 cells
An Integrated Bioinformatics Approach Identifies Elevated Cyclin E2 Expression and E2F Activity as Distinct Features of Tamoxifen Resistant Breast Tumors. . 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.
In this report, we show that overexpression of the LMW forms of cyclin E render letrozole therapy ineffective in breast cancer cells that express both aromatase and ER. The mechanism of this effect is through the LMW cyclin E-mediated induction of the CDK2 activity. When LMW cyclin E is present, it results in higher CDK2 activity and resistance to p21 and p27 inhibition. Treatment of cells with letrozole leads to increased binding of p27 to CDK2, resulting in the inactivation of CDK2. An event such as overexpression of LMW cyclin E, which can bypass this process, will render letrozole ineffective in mediating a growth arrest in these cells. We also show that treatment of cells with roscovitine can overcome this LMW cyclin E-mediated letrozole resistance. As such, our data provide an alternative treatment option for those postmenopausal breast cancer patients whose tumors are ER positive but express the LMW forms of cyclin E. We show that this subgroup of patients has a poor prognosis, with a ...
Breast cancer is one of the most common malignancies in women. Due to early detection and the use of screening programs approximately 60% of all new cases lack lymph node involvement. Today, a substantial proportion of these women will be offered adjuvant systemic chemotherapy. However, better proliferation markers are needed to predict patient outcome and to avoid overtreatment. Cyclin A, cyclin E and Ki-67 are all markers for proliferation and involved in the regulation of the cell cycle. Overexpression has been associated with disease recurrence in several studies, but the results have not been consistent. However, none of these studies has investigated aberrant expression of cyclin E (the expression of cyclin E during phases of the cell cycle other than late G1 and early S-phase). Studies have shown that aberrant cyclin E might provide additional prognostic information compared to cyclin E alone.. The aims of this thesis were 1.to investigate the prognostic value of cyclin A, cyclin E and ...
Cyclin E2, but not cyclin E1, is included in several gene signatures that predict disease progression in either tamoxifen-resistant or metastatic breast cancer. We therefore examined the role of cyclin E2 in antiestrogen resistance in vitro and its potential for therapeutic targeting through cyclin- …
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 ...
Although cyclin E1 overexpression is an important prognostic marker in breast and other cancers, the molecular cause(s) of these alterations was poorly understood. Our data show that the protein phosphatase PP2A-B55β regulates cyclin E1 levels in cellular division cycles and contributes to its dysregulation in cancers (Fig. 5D). During G1 phase, PP2A-B55β antagonizes phosphorylations of cyclin E1 mediated by autophosphorylation and GSK3 kinase, allowing for cyclin E1 to accumulate and initiate an S-phase program. After S-phase is initiated, B55β levels decline, which deprotects cyclin E1 from phosphorylation, thus triggering its recognition and ubiquitylation by SCFFbxw7. In support of a possible involvement of PP2A in cyclin E1 regulation, a recent report found that in yeast PP2ACdc55 controls the stability of G1 cyclin Cln2 through regulation of its phosphorylation state (27). In cancers, this regulation can be aberrant and augmented B55β expression functions to antagonize cyclin E1 ...
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).
Cyclin E, one of the activators of the cyclin-dependent kinase Cdk2, is expressed near the G1-S phase transition and is thought to be critical for the initiation of DNA replication and other S-phase functions. Accumulation of cyclin E at the G1-S boundary is achieved by periodic transcription couple …
3197 Cyclin E, a regulatory subunit of CDK2 has key S phase promoting functions in normal cells. Cyclin E is often overexpressed and present in low molecular weight (LMW) isoforms in malignant cells and such deregulation is associated with aggressive disease and poor outcome. Stable overespression of LMW cyclin E in breast cancer cells promotes chromosome instability in breast cancer cells. Examination of human cancer tissues and cultured cells has revealed a significant correlation between loss and/or mutation of tumor suppressor p53 and occurrence of centrosome amplification. We hypothetized that cyclin E LMW overexpression together with p53 depletion, cooperate to efficiently induce spindles abnormalities and centrosome amplification leading to chromosomal instability. To test this hypothesis we generated a model system composed of MCF-7 cells, which inducibly overexpress the LMW cyclin E protein under control of tetracycline-inducible promoter. Short-term induction of LMW of cylin E for 24 ...
Overexpressed cyclin E in tumours is a prognosticator for poor patient outcome. Cells that overexpress cyclin E have been shown to be impaired in S-phase progression and exhibit genetic instability that may drive this subset of cancers. However, the
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Sigma-Aldrich offers abstracts and full-text articles by [Ning-Ai Liu, Takako Araki, Daniel Cuevas-Ramos, Jiang Hong, Anat Ben-Shlomo, Yukiko Tone, Masahide Tone, Shlomo Melmed].
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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The recent discovery and characterization of RNA interference (RNAi) provides us with a new tool for gene inactivation and cancer gene therapy. Here, we have investigated the effect of knocking down target proteins by short hairpin RNAs (shRNAs) expressed from viral vectors. The senescence process of primary cell cultures occurs after a finite proliferative doublings. In the present study, we tested a new strategy for mouse primary cultures immortalization using a retrovirus carrying the shRNA sequence against the p53 wild type protein. The inhibition of over 80 % of p53 in murine primary cells leads to cell immortalization. We have also constructed retrovirus to inhibit other target proteins to use as potential cancer gene therapy weapons. Cyclin E1 is expressed during the late G1 phase of the cell cycle and mediates the initiation of DNA synthesis by activating cyclin-dependent kinases 2 (CDK2). We found that the knockdown of cyclin E1 in cancer cells triggers considerable apoptotic induction. ...
In that study MCM7 and cyclin E proteins were found to be elevated in the epithelium lining the K14E6 mouse cervix and vagina ...
I am 2 weeks post surgery and started on the following rehab: Stretches x 3 times a day Cycling 15 minutes at 15km per hour (it is hard cycline
PRIMARY OBJECTIVES:. I. To determine the maximum tolerated dose (MTD) of dinaciclib given in combination with epirubicin in patients with metastatic triple negative breast cancer.. SECONDARY OBJECTIVES:. I. To determine the predictive value of myeloid cell leukemia sequence 1 protein (MCL-1), low molecular weight cyclin E (LMW-E), and tumor grade as predictors of biologic response (i.e. induction of apoptosis) in tumors treated with therapy.. II. To evaluate the efficacy of combination therapy. III. To determine the effects of therapy on proliferation as measured by proliferation-related Ki-67 antigen (Ki67) and apoptosis as measured by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay (TUNEL).. OUTLINE: This is a dose-escalation study of dinaciclib.. Patients receive dinaciclib intravenously (IV) over 2 hours on day 1 and epirubicin hydrochloride IV over 30 minutes on day 2. Treatment repeats every 21 days for up to 12 courses in the absence of disease ...
PRIMARY OBJECTIVES:. I. To determine the maximum tolerated dose (MTD) of dinaciclib given in combination with epirubicin in patients with metastatic triple negative breast cancer.. SECONDARY OBJECTIVES:. I. To determine the predictive value of myeloid cell leukemia sequence 1 protein (MCL-1), low molecular weight cyclin E (LMW-E), and tumor grade as predictors of biologic response (i.e. induction of apoptosis) in tumors treated with therapy.. II. To evaluate the efficacy of combination therapy. III. To determine the effects of therapy on proliferation as measured by proliferation-related Ki-67 antigen (Ki67) and apoptosis as measured by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay (TUNEL).. OUTLINE: This is a dose-escalation study of dinaciclib.. Patients receive dinaciclib intravenously (IV) over 2 hours on day 1 and epirubicin hydrochloride IV over 30 minutes on day 2. Treatment repeats every 21 days for up to 12 courses in the absence of disease ...
Cholangiocarcinoma (CC) is characterized by a high degree of genetic instability, which is believed to contribute to its resistance towards therapeutic interventions. We have recently shown that expression of the intracellular domain of the Notch1 receptor (NICD) in mice leads to the formation of intrahepatic cholangiocarcinoma (ICC) which originates from hepatic progenitor cells. These ICC are characterized by their high expression of Cyclin E and a dramatically increased level of DNA damage. We showed that Notch directly transactivates the Cyclin E promoter and that Cyclin E is the critical downstream target of Notch induced transformation in ICC. Cyclin E exerts its oncogenic function through an acceleration of the cell cycle (in complex with cdk2) and through its ability to induce replicative stress and DNA damage. Cyclin E/cdk2 complexes are in turn inhibited by the cyclin kinase inhibitor (cki) p27kip1. While the ability of p27 to act as a cki is well established, we recently identified in ...
Productive infections by human papillomaviruses (HPVs) occur only in differentiated keratinocytes in squamous epithelia in which the HPV E7 protein reactivates the host DNA replication machinery to support viral DNA replication. In a fraction of the differentiated keratinocytes, E7 also posttranscriptionally induces p21cip1, which is distributed in a mutually exclusive manner with unscheduled cellular DNA synthesis. In this study, double immunofluorescence labeling unexpectedly revealed that E7 caused a concordant accumulation of both cyclin E and p21cip1 to high levels in patient papillomas and in organotypic cultures of primary human keratinocytes. The induction of cyclin E is mutually exclusive with unscheduled cellular DNA synthesis or abundant viral DNA. These novel virus-host interactions in differentiated keratinocytes are in contrast to previous observations made in submerged proliferating cultures, in which HPV E7 induces cyclin E and overcomes p21cip1 inhibition of S-phase entry. We ...
In animal cells, the interphase centrosome reproduces or duplicates only once per cell cycle, thereby ensuring a strictly bipolar mitotic spindle axis (1). Because there is no cell cycle checkpoint that monitors the number of spindle poles (2), uncontrolled duplication of the centrosome can contribute to genomic instability through the formation of multipolar mitotic spindles. Indeed, many human tumor cells, including those lacking the tumor suppresser protein p53 (3), have abnormally high numbers of centrosomes (4).. Studies of sea urchin and Xenopus embryos and clam oocyte lysates have revealed that the centrosome cycle can be regulated solely by cytoplasmic mechanisms (5-8): The repeated duplication of the centrosome proceeds in the complete absence of either a nucleus (7) or protein synthesis (8). In theory, the cyclical rise and fall in the activity of one or more cyclin-dependent kinases (Cdks) could be the cytoplasmic mechanism that coordinates centrosome reproduction with cell cycle ...
Disease progression in B-cell chronic lymphocytic leukaemia (B-CLL) is determined by the interplay between proliferation kinetics in the proliferating compartment and cell death in the accumulating compartment. Improving our knowledge of cell cycle regulation in B-CLL cells might therefore be important for identifying therapeutic targets. Cyclin E was detected by Western blotting in purified B-CLL cells from peripheral blood samples of all 12 patient tested but not in normal peripheral blood B cells. While cyclin-dependent kinase 2 (cdk2) expression was similar in different samples, p27 and cyclin E expression was highly variable. We further investigated the regulation of p27, cyclin E and cdk2 in an in vitro model of cycling B-CLL cells. Cyclin E and cdk2 expression was increased in B-CLL cells stimulated with a CpG-oligodeoxynucleotide and interleukin-2, while p27 expression rapidly declined. This was accompanied by the increased formation of cyclin E-cdk2 complexes, which were able to ...
To distinguish whether the increased Cdk2 activity is due to an immediate effect of PP2A inhibition on CycE/Cdk2, we performed a kinase assay in Drosophila S2R+ cultured cells, where we can use short-term treatments with the pan-PP2A inhibitor okadaic acid (OA) to discern immediate versus indirect effects of PP2A inhibition on CycE/Cdk2 activity. We performed a timecourse and dosage test of OA treatment in S2R+ cells and confirmed that, with 30 min of OA treatment, PP2A activity is inhibited as assessed by increased phosphorylation of S6K. We performed a timecourse of OA treatment on S2R+ cells transiently transfected with a CycE expression vector and undertook CycE/Cdk2 kinase assays as described above. We found that with 30 min of OA treatment S2R+ cells exhibit a mild increase in CycE/Cdk2 activity (Fig. 8C), consistent with a direct effect of PP2A on CycE/Cdk2 activity. However, upon longer OA treatments (2 h shown), cells exhibit a reduction in CycE/Cdk2 kinase activity and a slower ...
Antigen Background p27 protein, also known as kinase inhibitory protein 1 (Kip1), binds to cyclin E/cdk2 complexes, but not to cdk2 alone, and is detected in purified extracts of growth-arrested cells. p27 protein constrains cell proliferation by setting the threshold level of cyclin E necessary to activate cdk2. The p27 protein is also present in proliferating cells, but only in a sequestered form when it is unavailable to interact with cyclin E/cdk2 complexes. It is likely that cyclin D complexed with catalytically inactive cdk4 is sufficient to sequester p27 protein and titrate its function. The presence of bound p27 protein in proliferating cells suggests that its role may not be restricted to inducing cell cycle arrest but to also set the cyclin E threshold for execution of the G1 to S phase transition during each mitotic cycle.. ...
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Several earlier studies suggested that the E-cyclins CcnE1 and CcnE2 are functionally equivalent (10). However, more recent work also identified nonredundant functions of either CcnE1 or CcnE2 (11). HCC is associated with strong CcnE1 overexpression correlating with poor prognosis of patients, while the contribution of CcnE2 for liver cancer has barely been investigated so far (5). In a recent and elegant study, Sicinski and coworkers (12) showed that compound deletion of CcnE1 and CcnE2 prevented HCC progression in mice and halted proliferation of human HCC cells. However, this important work does not answer the question of whether CcnE1 or CcnE2 may mediate individual functions in distinct stages of hepatocarcinogenesis, which was now extensively addressed in our present study.. In our present study, ablation of CcnE1 largely prevented the development of HCC in two independent tumor models, and previous analysis indicated that inhibition of CcnE1 may also attenuate hepatocarcinogenesis in an ...
Figure 2. MCPH1 protein expression of cyclin E, CDC25A and MPCH1 in astrocytoma and meningioma tumors. (a) Brain tumor cells (BTCs) with astrocytoma. 1: BTC with DAPI filter; 2: BTC conjugated with FITC presenting low expression of cyclin E; 3: BTC conjugated with R-PE presenting low expression of CDC25A; 4: BTC conjugated with PE-Cy5 reflecting low expression of MCPH1 (× 100). (b) BTCs with meningioma. 1: BTC with DAPI filter; 2: BTC conjugated with FITC presenting high expression of cyclin E; 3: BTC conjugated with R-PE presenting low expression of cyclin E in majority of cells accompanied by clone of cells with high expression; 4: BTC conjugated with PE-Cy5 reflecting high expression of MCPH1 (× 100). ...
Cyclin E2 antibody Rabbit Polyclonal from Proteintech validated in Western Blot (WB), Immunoprecipitation (IP), Immunohistochemistry (IHC), Immunofluorescence (IF), Flow Cytometry (FC), Enzyme-linked Immunosorbent Assay (ELISA) applications. This antibody reacts with human samples. Cat.No. 11935-1-AP.
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New research sheds light on a critical decision every newly born cell makes: whether to continue to proliferate or exit the cell-division cycle. In cancer, the equivalent of an on switch is stuck in that position. In healthy cells, the team has discovered, the opposing effects of proteins ORC1 and CDC6 in controlling the level of Cyclin E contributes to the stability of the genome.
When protein synthesis is completely blocked from before fertilization, the sea urchin zygote arrests in first S phase and the paternal centrosome reduplicates multiple times. However, when protein synthesis is blocked starting in prophase of first mitosis, the zygote divides and the blastomeres arrest in a G1-like state. The centrosome inherited from this mitosis duplicates only once in each blastomere for reasons that are not understood. The late G1 rise in cyclin E/cdk2 kinase activity initiates centrosome duplication in mammalian cells and its activity is needed for centrosome duplication in Xenopus egg extracts. Since the half-time for cyclin E turnover is normally approximately 1 h in sea urchin zygotes, the different behaviors of centrosomes during G1 and S phase arrests could be due to differential losses of cyclin E and its associated kinase activities at these two arrest points. To better understand the mechanisms that limit centrosome duplication, we characterize the levels of cyclin E and
This study examined how L-leucine affected DNA synthesis and cell cycle regulatory protein expression in cultured primary chicken hepatocytes. L-Leucine promoted DNA synthesis in a dose- and time-dependent manner, with concomitant increases in cyclin D1 and cyclin E expression. Phospholipase C (PLC) and protein kinase C (PKC) mediated the L-leucine-induced increases in [3H]-thymidine incorporation and cyclin D1/CDK4 and cyclin E/CDK2 expression, as U73122 (a PLC inhibitor) or bisindolylmaleimide I (a PKC blocker) inhibited these effects. L-Leucine also increased PKC phosphorylation and intracellular Ca2+ levels. L-Leucine-mediated increases in [3H]-thymidine incorporation and cyclin/CDK expression were sensitive to LY 294002 (PI3K inhibitor), Akt inhibitor, PD 98059 (MEK inhibitor). It was also observed that L-leucine-induced increases of cyclin/CDK expression were inhibited by PI3K siRNA and ERK siRNA; L-leucine increased extracellular signal-regulated kinases 1/2 (ERK1/2) and Akt ...
PYR-41 (50 μM) inhibits activity of ubiquitin-activating enzyme E1 by over 90%. PYR-41 could be a target for nucleophilic attack and potentially reacts with the active site cysteine of E1. PYR-41 efficiently blocks cyclin E degradation. PYR-41 decreases the level of E1fUb thioesters in cells with a IC50 of between 10 and 25 μM, and prevents proteasome inhibitor-induced accumulation of ubiquitylated proteins. PYR-41 increases total sumoylation in cells and in cell harboring temperature-sensitive E1. PYR-41 is able to inhibit both proteasome-dependent and proteasome-independent activities of ubiquitylation. PYR-41 (50 μM) attenuates 1 ng/mL IL-1α-mediated nuclear factor-κB activation by >60% through preventing the downstream ubiquitylation and proteasomal degradation of IκBα. PYR-41 inhibits degradation of p53 and activates the transcriptional activity of p53, which enable its differentially killing transformed p53-expressing cells. [1] PYR-41 blocks ubiquitination reactions but ...
Blocking oncogenic signaling induced by the BRAFV600E mutation is usually a promising approach for melanoma treatment. upon exposure to PLX4032 than resistant cell lines. In conclusion, BRAFV600E mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity. Background Improved knowledge of the oncogenic events in melanoma indicates that a majority of mutations activate the mitogen-activated protein kinase (MAPK) pathway [1,2]. The most frequent mutation in the MAPK pathway is in the BRAF gene, present in 60-70% of malignant melanomas [3]. NRAS mutations occur in approximately 15% of melanomas [1,4,5] and are mutually unique with BRAF mutations [6,7]. The majority of mutations in BRAF are accounted for by a single nucleotide transversion from thymidine to adenosine leading to a substitution of valine by glutamic acid at position 600 (termed BRAFV600E) [3,4,8], which leads to a 500-fold increase in activity ...
14-3-3 family proteins regulate multiple signalling pathways. Understanding biological functions of 14-3-3 proteins has been limited by the functional redundancy of conserved isotypes. Here we provide evidence that 14-3-3 proteins regulate two interacting components of Tor signalling in Drosophila, translationally controlled tumour protein (Tctp) and Rheb GTPase. Single knockdown of 14-3-3ɛ or 14-3-3ζ isoform does not show obvious defects in organ development but causes synergistic genetic interaction with Tctp and Rheb to impair tissue growth. 14-3-3 proteins physically interact with Tctp and Rheb. Knockdown of both 14-3-3 isoforms abolishes the binding between Tctp and Rheb, disrupting organ development. Depletion of 14-3-3s also reduces the level of phosphorylated S6 kinase, phosphorylated Thor/4E-BP and cyclin E (CycE). Growth defects from knockdown of 14-3-3 and Tctp are suppressed by CycE overexpression. This study suggests a novel mechanism of Tor regulation mediated by 14-3-3 ...
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 ...
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 ...
Pu-erh tea is definitely believed to possess health benefits, the growth inhibition activity of Pu-erh tea about breast cancer cell offers not been investigated. P-JNK, P-p53 Tonabersat (Ser15), g21, CyclinD1 and CyclinE by Pu-erh tea remove. Our outcomes indicate that Pu-erh tea drinking water remove prevents cell expansion of MDA-MB-231 cells through the induction of […]. ...
In this paper, we report that (+)-preussin, a pyrrolidinol alkaloid originally identified as an antifungal agent, has growth-inhibitory and cytotoxic effects on human cancer cells. Preussin was found to be a potent inhibitor of cyclin E kinase (CDK2-cyclin E) in vitro (50% inhibitory concentration; approximately 500 nM) and to inhibit cell cycle progression into S phase. In agreement with these findings, the level of the cyclin-dependent kinase inhibitor p27(KIP-1) is increased in response to preussin treatment while the expression of both cyclin A and the transcription factor E2F-1 is down-regulated. Preussin also induces programmed cell death (apoptosis), which requires caspase activation and involves the release of cytochrome c from mitochondria. This induction of apoptosis is not blocked by high levels of Bcl-2, which usually confers resistance to chemotherapeutic agents. Taken together, our data indicate that preussin could be a promising lead compound for the development of a new class of potent
The representation of cyclins and cyclin-dependent kinases (cdks) was analyzed during progressive development of the bone cell phenotype in cultures of normal diploid rat calvarial osteoblasts. Three developmental stages were examined: (a) proliferation; (b) monolayer confluency; and (c) mineralization of the bone extracellular matrix. We demonstrate that the presence of cyclins and cdks is not restricted to the proliferation period. Consistent with their role in cell cycle progression, cdc2 and cdk2 decrease postproliferatively. However, cdk4 and cyclins A, B, and D1 persist in confluent cells. Cyclin E is significantly up-regulated during the extracellular matrix mineralization developmental period. Examination of the cytoplasmic levels of these cell cycle regulatory proteins indicates a marked increase in cyclin B in the late differentiation stage. The elevation of nuclear cyclin E and cytoplasmic cyclin B is not observed in osteoblasts maintained under culture conditions that do not support
The spacer region of pRb2/p130 was reported to be able to inhibit the kinase activity of Cdk2. The region responsible for the inhibitory effect was further narrowed down to a 39-amino-acid sequence, which was named as Spa310. In this dissertation, the anti-cancer functions and mechanisms of Spa310 were studied. The synthesized Spa310 peptide was able to inhibit the kinase activities of Cdk2/Cyclin E/A complexes. In vitro kinase assays showed the inhibition occurred in a dose-dependent manner. The half maximal inhibition concentration of the Spa310 in the kinase assay was 1.67mM. In addition, it has been shown that Spa310 peptide is able to inhibit the kinase activities of both Cdk2/Cyclin E and Cdk2/Cyclin A. Intra-cellular distribution study using fluorescein-labeled Spa310 peptide showed that Spa310 was able to localize to the nuclei of A549 cancer cells. Some data indicated the endoplasmic reticulum might play a role in transporting Spa310 peptide from cytoplasm to the nucleus. At high ...
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. ...
TABLE-US-00006 TABLE 6 THI + 2 + 4 + 5 + 7 Composite (Meta-THc) OG- OG- OG- OG- OG- 3116 @ 3116 @ 3116 @ 3116 @ 3116 @ 50 100 1 μg/ml 5 μg/ml 25 μg/ml μg/ml μg/ml Abl(H396P)(h) 91 88 73 55 50 Abl(M351T)(h) 100 87 62 50 38 Abl(Q252H)(h) 89 86 58 45 44 Abl(h) 98 85 65 41 49 Abl(m) 99 87 60 47 43 Abl(T315I)(h) 100 91 79 65 52 Abl(Y253F)(h) 93 90 75 54 51 ACK1(h) 122 112 97 102 82 ALK(h) 76 38 17 16 26 ALK4(h) 96 95 85 68 48 Arg(h) 94 91 68 52 42 Arg(m) 100 99 94 73 50 ARK5(h) 100 97 82 64 75 Aurora-A(h) 92 79 40 41 27 Axl(h) 97 99 83 77 60 Blk(m) 95 102 71 49 54 Bmx(h) 91 94 84 77 43 BrSK1(h) 95 90 71 47 51 BrSK2(h) 91 82 77 70 63 BTK(h) 99 97 64 44 28 CaMKI(h) 95 84 46 28 48 CaMKII(r) 97 106 89 69 63 CaMKIIβ(h) 94 99 85 52 34 CaMKIIγ(h) 107 103 94 92 134 CaMKIIδ(h) 103 97 84 83 84 CaMKIV(h) 107 108 95 75 58 CaMKIδ(h) 91 93 92 75 80 CDK1/cyclinB(h) 99 101 91 71 58 CDK2/cyclinA(h) 105 106 92 83 63 CDK2/cyclinE(h) 99 103 75 60 42 CDK3/cyclinE(h) 108 100 96 79 45 CDK5/p25(h) 102 89 84 77 72 ...
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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。
Die Universität zu Köln ist eine Exzellenzuniversität mit dem klassischen Fächerspektrum einer Volluniversität. Als eine der größen Hochschulen Europas arbeitet sie in Forschung und Lehre auch international auf höchstem Niveau.
マウス・モノクローナル抗体 ab38 交差種: Ms,Rat,Hu 適用: WB,IP,IHC-P,IHC-Fr,Flow Cyt…Cyclin A2抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody…
cyclin-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 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". www.ncbi.nlm.nih.gov. Retrieved 2016-10-11. ... CDKN2A, also known as cyclin-dependent kinase inhibitor 2A, is a gene which in humans is located at chromosome 9, band p21.3. ... "CDKN2A - Cyclin-dependent kinase inhibitor 2A - Homo sapiens (Human) - CDKN2A gene & protein". www.uniprot.org. Retrieved 2016- ...
2004). "Characterization of cyclin L2, a novel cyclin with an arginine/serine-rich domain: phosphorylation by DYRK1A and ... "Entrez Gene: CCNL1 cyclin L1". Human CCNL1 genome location and CCNL1 gene details page in the UCSC Genome Browser. Zhang QH, Ye ... Cyclin-L1 is a protein that in humans is encoded by the CCNL1 gene. GRCh38: Ensembl release 89: ENSG00000163660 - Ensembl, May ... 2006). "Cyclin L1 (CCNL1) gene alterations in human head and neck squamous cell carcinoma". Br. J. Cancer. 94 (7): 1041-4. doi: ...
He holds a US and international patent on Activators of Cyclin-Dependent Kinases (ACDK) and has mentored many doctoral scholars ... 19-. ISBN 978-94-007-0265-3. She, Jin-Xiong; Wang, Cong-Yi; Kumar, G. Pradeep (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 ...
... 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 ...
First, cyclin must bind to the Cdk. In the second step, CAK must phosphorylate the cyclin-Cdk complex on the threonine residue ... In budding yeast, activating phosphorylation by CAK can take place before cyclin binding. In both humans and yeast, cyclin ... Since Cdks need to be free of Cdk inhibitor proteins (CKIs) and associated with cyclins in order to be activated, CAK activity ... Lolli G, Johnson LN (April 2005). "CAK-Cyclin-dependent Activating Kinase: a key kinase in cell cycle control and a target for ...
In the late G2 phase, it is present as an inactive complex of tyrosine-phosphorylated p34cdc2 and unphosphorylated cyclin ... Meijer L, Azzi L, Wang JY (1991). "Cyclin B targets p34cdc2 for tyrosine phosphorylation". EMBO J. 10 (6): 1545-54. doi:10.1002 ...
Xu W, Ji JY (2011). "Dysregulation of CDK8 and Cyclin C in tumorigenesis". J Genet Genomics. 38 (10): 439-52. doi:10.1016/j.jgg ... Another example of structural variability is seen in vertebrates, in which 3 paralogues of subunits of the cyclin-dependent ...
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 cox.net Sun Mar 3 16:33:22 EST 2002 *Previous message: THE SECRET the IRS is TERRIFIED ... But, with Cyclin E antibodies, we get cytoplasmic staining rather than nuclear staining which is mentioned in all the ...
CYCLIN; Cyclin box fold. Protein binding domain functioning in cell-cycle and transcription control. Present in cyclins, TFIIB ... CYCLIN; Cyclin box fold. Protein binding domain functioning in cell-cycle and transcription control. Present in cyclins, TFIIB ... CYCLIN; Cyclin box fold. Protein binding domain functioning in cell-cycle and transcription control. Present in cyclins, TFIIB ... Cyclin I: a new cyclin encoded by a gene isolated from human brain. Nakamura T, et al. Exp Cell Res, 1995 Dec. PMID 7493655 ...
Comparison of the structure of the unbound cyclin with the structure of cyclin A complexed with CDK2 reveals that cyclin A does ... cyclin A-3, corresponding to residues 171-432 of human cyclin A. The cyclin box has an alpha-helical fold comprising five alpha ... Cyclins exhibit diverse sequences but all share homology over a region of approximately 100 amino acids, termed the cyclin box ... The structural results indicate a role for the cyclin-box fold both as a template for the cyclin family and as a generalised ...
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 jhunix.hcf.jhu.edu Fri Oct 6 15:33:24 EST 1995 *Previous message: luciferase ... My problem: I cant find the nucleotide and amino acid sequences for the Cyclin H gene (the human counterpart to CCL1) and its ...
Cyclin-Up Inn 3 br home overlooking Whalan and the Root River Trail, Pet Friendl. The house sleeps 8 in 3 queen sized beds and ... Cyclin-Up Inn 3 br home overlooking Whalan and the Root River Trail, Pet Friendl. The house sleeps 8 in 3 queen sized beds and ... Cyclin-Up Inn 3 br home overlooking Whalan and the Root River Trail, Pet Friendl. The house sleeps 8 in 3 queen sized beds and ... Cyclin-Up Inn 3 br home overlooking Whalan and the Root River Trail, Pet Friendl. The house sleeps 8 in 3 queen sized beds and ...
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 my-dejanews.com balczonr at my-dejanews.com Tue Sep 22 13:25:16 EST 1998 ...
Cyclin-dependent kinase synonyms, Cyclin-dependent kinase pronunciation, Cyclin-dependent kinase translation, English ... dictionary definition of Cyclin-dependent kinase. n. Any of various enzymes that catalyze the transfer of a phosphate group ... Targeting cyclins and cyclin-dependent kinases in cancer: lessons from mice, hopes for therapeutic applications in human.. The ... STRUCTURAL STUDIES OF CYCLIN-DEPENDENT KINASE INHIBITORS: DYNAMICS AND FLEXIBILITY ARE THE STORY.. STRUCTURAL STUDIES OF CYCLIN ...
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: https://www.reportbuyer.com/product/5190761 Summary Cyclin Dependent Kinase 9 (Tat Associated Kinase ... This protein forms a complex with and is regulated by its regulatory subunit cyclin T or cyclin K. HIV-1 Tat protein was found ... The latest report Cyclin Dependent Kinase 9 - Pipeline Review, H2 2017, outlays comprehensive information on the Cyclin ... Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase ...
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 . (wikipedia.org)
  • Cyclins function as regulators of CDK kinases. (wikipedia.org)
  • They act in conjunction with cyclin-dependent protein kinases, which are proteins that phosphorylate other proteins. (encyclopedia.com)
  • What are Cyclin-Dependent Kinases? (news-medical.net)
  • Cyclin-dependent kinases are a type of serine/threonine kinase which are activated by cyclins to drive the progress of the cell cycle. (news-medical.net)
  • Cyclin dependent kinases are present at constant levels throughout the cell cycle, but are only active in the presence of cyclins. (news-medical.net)
  • Eukaryotic cell cycle progression is regulated by cyclin dependent protein kinases (CDKs) whose activity is regulated by association with cyclins and by reversible phosphorylation. (nih.gov)
  • 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 ). (pnas.org)
  • 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. (pnas.org)
  • 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. (springer.com)
  • Targeting cyclins and cyclin-dependent kinases in cancer: lessons from mice, hopes for therapeutic applications in human. (thefreedictionary.com)
  • This is known as the cell cycle and cyclins and their partners, cyclin-dependant kinases, are its master control proteins. (eurekalert.org)
  • 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. (genomeweb.com)
  • Cyclin-dependent kinases (CDKs) typically bind cyclins and regulate a number of downstream proteins that are key components of cell division and transcription. (genomeweb.com)
  • 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). (atlasgeneticsoncology.org)
  • 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). (atlasgeneticsoncology.org)
  • 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. (ingentaconnect.com)
  • 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. (nature.com)
  • They also interact with cyclin-dependent kinases to control cell cycle progression in plants. (mdpi.com)
  • 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. (novusbio.com)
  • Cyclins are characterized by a dramatic periodicity in protein abundance throughout the cell cycle and function as regulators of CDK kinases. (rockland-inc.com)
  • CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. (researchandmarkets.com)
  • Cyclins are regulatory subunits of the cyclin-dependent kinases (cdks) and they control transition at different specific phases of the cell cycle. (fishersci.com)
  • The key cell-cycle regulator Cdc2 belongs to a family of cyclin-dependent kinases in higher eukaryotes. (sciencemag.org)
  • 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. (sciencemag.org)
  • The induction of cyclin D1 can also be mediated by a target of p53, the p21 (WAF1/CIP1) inhibitor of cyclin-dependent kinases. (aacrjournals.org)
  • Cyclins bind to and regulate the activity of the Cyclin dependent protein kinases (CDKs). (thermofisher.com)
  • 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. (ahajournals.org)
  • Cyclins are eukaryotic proteins that play an active role in controlling nuclear cell division cycles [ ( PUBMED:12910258 ) ], and regulate cyclin dependent kinases (CDKs). (embl.de)
  • Cyclins, together with the p34 (cdc2) or cdk2 kinases, form the Maturation Promoting Factor (MPF). (embl.de)
  • 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). (encyclopedia.com)
  • 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. (pnas.org)
  • 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. (pnas.org)
  • 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. (eurekalert.org)
  • 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. (fiercebiotech.com)
  • More research is needed, but assessing levels of cyclin D1 at diagnosis could help to personalize treatment. (fiercebiotech.com)
  • Of the seven patients who had a recurrence, six had high levels of cyclin E activity. (scienceblog.com)
  • 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. (diabetesjournals.org)
  • Human prostate carcinoma cell lines frequently express elevated levels of cyclin D1 protein, although the gene is not amplified in these cells ( 18 ). (aacrjournals.org)
  • Cyclin A is also produced, which binds to CDK2 and stimulates DNA replication. (news-medical.net)
  • 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. (nih.gov)
  • 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. (nih.gov)
  • Where examined, both Cdc2 and Cdk2, the catalytic subunits known to associate with cyclin A, were activated. (pnas.org)
  • However, their research also showed that treating breast cancer cells with a cyclin-dependent kinase 2 (CDK2) inhibitor can reverse letrozole resistance. (scienceblog.com)
  • 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. (scienceblog.com)
  • 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. (scienceblog.com)
  • 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. (atlasgeneticsoncology.org)
  • 2005). Human cyclin A1 interacts with CDK2 in vitro and in vivo (Yang et al. (atlasgeneticsoncology.org)
  • 2001). Moreover the cyclin A1-CDK2 complex regulates DNA double-strand break repair following radiation damage (Müller-Tidow et al. (atlasgeneticsoncology.org)
  • 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. (atlasgeneticsoncology.org)
  • CDK2 is a catalytic subunit of the cyclin-dependent protein kinase complex, and is essential for cell cycle G1⁄S phase transition. (fishersci.ca)
  • Cdk2 and cyclin E, long thought to be essential, are largely dispensable. (sciencemag.org)
  • Cyclin E forms a complex with and functions as a regulatory subunit of CDK2, whose activity is required for cell cycle G1/S transition. (thermofisher.com)
  • Cyclin A binds to S phase Cdk2 and is required for the cell to progress through the S phase. (rockland-inc.com)
  • Cyclin A/ Cdk2 is inhibited by the complex p21CIP. (rockland-inc.com)
  • 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. (rockland-inc.com)
  • The Cyclin E/CDK2 complex phosphorylates p27Kip1, tagging it for degradation, thus promoting expression of Cyclin A, allowing progression to S phase. (rockland-inc.com)
  • Hbo1 is a cyclin E/CDK2 substrate that enriches breast cancer stem-like cells. (semanticscholar.org)
  • Cyclin is a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes . (wikipedia.org)
  • For example, the amino-terminal regions of S and M cyclins contain short destruction-box motifs that target these proteins for proteolysis in mitosis. (wikipedia.org)
  • cyclin Any of a family of proteins that help control the various phases of the cell cycle . (encyclopedia.com)
  • 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. (wikipedia.org)
  • Once bound to a cyclin they act to phosphorylate many target proteins on serine or threonine amino acid residues. (news-medical.net)
  • 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. (news-medical.net)
  • 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. (bio.net)
  • Threading analysis shows that the cyclin-box fold is consistent with the sequences of the transcription factor TFIIB and other functionally related proteins. (nih.gov)
  • Molecular analyses revealed that cells lacking cyclin E fail to normally incorporate MCM proteins into DNA replication origins during G(0)-->S progression. (uniprot.org)
  • The work supports the idea that cancer-causing proteins like cyclin D1 may drive cancer progression in part via miRNA biogenesis. (eurekalert.org)
  • 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. (eurekalert.org)
  • Cyclin E is one of the proteins that regulates the cell cycle, influencing how rapidly a cell passes through the four phases and divides. (scienceblog.com)
  • 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. (novusbio.com)
  • After incubation with cell lysates, both phospho and nonphospho cyclin D1 proteins are captured by the coated antibody. (cellsignal.com)
  • Transcription of these particular cyclins is proposed to monitor the growth factor signal and the encoded proteins participate in G1 progression. (bl.uk)
  • Additionally we are shipping Cyclin H Antibodies (129) and Cyclin H Proteins (15) and many more products for this protein. (antibodies-online.com)
  • Additionally we are shipping Cyclin K Kits (12) and Cyclin K Proteins (7) and many more products for this protein. (antibodies-online.com)
  • Proteolytically processed forms of cyclin E proteins, which are specifically generated in tumors that overexpress cyclin E proteins. (semanticscholar.org)
  • There are 14939 Cyclin_C domains in 14900 proteins in SMART's nrdb database. (embl.de)
  • Taxonomic distribution of proteins containing Cyclin_C domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with Cyclin_C domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing Cyclin_C domain in the selected taxonomic class. (embl.de)
  • Cyclins themselves have no enzymatic activity but have binding sites for some substrates and target the Cdks to specific subcellular locations. (wikipedia.org)
  • These cyclins oscillate, increasing and decreasing at different stages, binding to CDKs and driving the cell cycle forward. (news-medical.net)
  • In addition to cyclin levels, this provides and additional way to control the activity of CDKs. (news-medical.net)
  • Cyclins also determine the subcellular location and substrate specificity of CDKs. (nih.gov)
  • O ciclo de pilha é regulado pelos cyclins, um tipo de proteína que liga e activa quinase do dependente do cyclin (CDKs). (news-medical.net)
  • Cyclins não tem nenhuma função enzimático do seus próprios, e liga-a pelo contrário a CDKs para ativá-los. (news-medical.net)
  • 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. (springer.com)
  • For example, although Cdks appear to be highly conserved phylogenetically, cyclins are much less so. (springer.com)
  • 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. (genomeweb.com)
  • 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. (genomeweb.com)
  • They identified more than two dozen CDKs and cyclins that were recurrently altered. (genomeweb.com)
  • Cell cycle-linked CDKs and cyclins were often amplified in cancers, but transcription-linked CDKs and cyclins tended to experience copy number losses. (genomeweb.com)
  • 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. (genomeweb.com)
  • The temporal expression of cyclins is tightly regulated and subsequently plays a critical role in controlling the enzymatic activity of cdks. (fishersci.com)
  • Multiple cyclins activate CDKs in all eukaryotes, but it is unclear whether multiple cyclins are really required for cell cycle progression. (biomedsearch.com)
  • 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. (antibodies-online.com)
  • There are currently no images for Cyclin C Antibody (NB120-2950). (novusbio.com)
  • Western Blot: Cyclin A1 Antibody [NBP1-02902] - Cyclin A1 western with U2OS cells. (novusbio.com)
  • Immunohistochemistry-Paraffin: Cyclin A1 Antibody [NBP1-02902] - Human testis after heat-induced antigen retrieval. (novusbio.com)
  • 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. (cellsignal.com)
  • A Cyclin D1 Rabbit Antibody has been coated onto the microwells. (cellsignal.com)
  • Following extensive washing, Cyclin D1 Mouse Detection Antibody is added to detect the captured cyclin D1 protein. (cellsignal.com)
  • The following product was used in this experiment: Cyclin E1 Monoclonal Antibody (4H7) from Thermo Fisher Scientific, catalog # BSM-52048R. (thermofisher.com)
  • The following product was used in this experiment: Cyclin B1 Polyclonal Antibody from Thermo Fisher Scientific, catalog # 55004-1-AP. (thermofisher.com)
  • WB analysis of extracts from various cell lines using Cyclin H antibody. (genetex.com)
  • ICC/IF analysis of HeLa cells using Cyclin H antibody (green) and DAPI (blue). (genetex.com)
  • Cyclin B1 antibody detects Cyclin B1 protein at cytoplasm on mouse ovary by immunohistochemical analysis. (genetex.com)
  • But, with Cyclin E antibodies, we get cytoplasmic staining rather than nuclear staining which is mentioned in all the literature I have read. (bio.net)
  • Anti-Cyclin K antibodies are available from several suppliers. (biocompare.com)
  • Your search returned 117 Cyclin K Antibodies across 20 suppliers. (biocompare.com)
  • Your search returned 1 cyclin Q Antibodies across 1 supplier. (biocompare.com)
  • Anti-Cyclin Antibodies are ideal for investigators involved in Cell Signaling, cell biology and Signal Transduction research. (rockland-inc.com)
  • On www.antibodies-online.com are 17 Cyclin H (CCNH) ELISA Kits from 4 different suppliers available. (antibodies-online.com)
  • Tumor samples were immunostained for cyclin B using commercial antibodies. (kb.se)
  • This cyclin shows the highest similarity with cyclin G. The transcript of this gene was found to be expressed constantly during cell cycle progression. (nih.gov)
  • Cyclin I is involved in the regulation of cell cycle progression. (nih.gov)
  • 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. (jci.org)
  • 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. (sciencemag.org)
  • These observations show that cyclin levels can be rate-limiting for G1 progression in mammalian cells and suggest that cyclin synthesis may be the target of physiological signals that control cell proliferation. (sciencemag.org)
  • 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. (atlasgeneticsoncology.org)
  • Taken together, our results demonstrate that cyclin D2 has a critical role in cell cycle progression and the tumorigenicity of GSCs. (nature.com)
  • D-type cyclins are known to have critical roles in cell cycle progression. (nature.com)
  • Because cyclin A2 was stimulated by cAMP, we assessed the role of cylcin A2 in cell cycle progression in Min6 and isolated islet β-cells. (diabetesjournals.org)
  • Cyclin E is an important regulator of cell cycle progression. (springer.com)
  • Destruction of Cyclin B1 is required for cell cycle progression. (thermofisher.com)
  • Cyclin E deregulation impairs mitotic progression through premature activation of Cdc25C. (semanticscholar.org)
  • We hypothesized that intrapituitary cyclin E signaling regulates corticotroph tumor POMC transcription independently of cell cycle progression. (sigmaaldrich.com)
  • A gene on chromosome 9q34.1 that encodes a cyclin-dependent kinase, which regulates cell cycle progression. (thefreedictionary.com)
  • 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. (aacrjournals.org)
  • However, the relationship between cyclin D1 expression and prostate tumor progression has yet to be clearly characterized. (aacrjournals.org)
  • 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). (wiley.com)
  • Using antisense RNA, Dr. Pestell's group was the first to show that cyclin D1 drives mammary tumor growth in vivo. (eurekalert.org)
  • 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 . (nature.com)
  • 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. (kb.se)
  • Western blotting was used to measure cyclin-dependent kinase (CDK) inhibitors p21 and p27 that arrest cell cycle. (thefreedictionary.com)
  • p27(KIP1) is a member of the CIP1/KIP1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. (thefreedictionary.com)
  • Some of the non-biological drugs, known as Cyclin-dependent kinase (CDK) inhibitors, are currently being tested for use in cancer treatment. (thefreedictionary.com)
  • 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. (thefreedictionary.com)
  • in opposition to this idea, it has been argued that cyclins might target the activated CDK to particular substrates or inhibitors. (biomedsearch.com)
  • 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. (biomedsearch.com)
  • 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. (sigmaaldrich.com)
  • 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. (embl.de)
  • 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. (wikipedia.org)
  • 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. (sciencemag.org)
  • These cyclin/cdk complexes are essential for passage through specific stages in the cell cycle. (fishersci.com)
  • Cyclin B1 complexes with p34 (cdc2) to form the maturation-promoting factor (MPF). (thermofisher.com)
  • SETD1A and cyclin K complexes may represent a therapeutic opportunity for acute myeloid leukemia and, potentially, for other cancers. (antibodies-online.com)
  • Cyclin K-containing kinase complexes maintain self-renewal in murine embryonic stem cells. (antibodies-online.com)
  • It is known that the cell cycle and cell proliferation are regulated by the sequential activation of cyclin-dependent kinase/cyclin complexes. (wiley.com)
  • This cyclin and its kinase partner are components of TFIIH, as well as RNA polymerase II protein complexes. (genetex.com)
  • Cyclin B1 is the regulatory subunit of the cdc2 kinase and is a protein required for mitotic initiation. (pnas.org)
  • 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. (medindia.net)
  • 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). (abcam.com)
  • 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. (sciencemag.org)
  • 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. (rockland-inc.com)
  • 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. (news-medical.net)
  • These genes include cyclin E, which binds to CDK4, driving the cell cycle into the S phase. (news-medical.net)
  • 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. (genomeweb.com)
  • Here, we have investigated a series of 110 primary malignant gliomas and 8 glioma cell lines for amplification and expression of the D‐type cyclin genes CCND1 (11q13), CCND2 (12p13), and CCND3 (6p21). (ingentaconnect.com)
  • 5 Three D-type cyclins, cyclin D1, D2 and D3, are encoded by distinct genes, but show significant amino-acid similarity. (nature.com)
  • Our genome-wide analysis identified 52 expressed cyclin genes in tomato. (mdpi.com)
  • Quantitative real-time polymerase chain reaction analysis indicates that the expression patterns of tomato cyclin genes were significantly different in vegetative and reproductive stages. (mdpi.com)
  • Transcription of most cyclin genes can be enhanced or repressed by exogenous application of gibberellin, which implies that gibberellin maybe a direct regulator of cyclin genes. (mdpi.com)
  • Cyclin C was originally identified by a genetic screen for human and Drosophila cDNAs that complement a triple knock-out of the CLN genes in Saccharomyces cerevisiae. (novusbio.com)
  • The treatment of quiescent cells with growth factors results in the transcriptional activation of the D-type cyclin genes during G1. (bl.uk)
  • Comparison of these results with those for the cyclin D1 and D2 genes should elucidate how transcription of these genes is co-ordinately regulated by growth factors. (bl.uk)
  • 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. (sigmaaldrich.com)
  • 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. (sigmaaldrich.com)
  • The Saccharomyces cerevisiae C-type cyclin and its cyclin-dependent kinase (Cdk8p) repress the transcription of several stress response genes. (genetics.org)
  • A cyclin forms a complex with Cdk, which begins to activate but the complete activation requires phosphorylation, as well. (wikipedia.org)
  • Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. (addgene.org)
  • 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 . (antibodies-online.com)
  • 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. (mdpi.com)
  • RV-cyclin does not increase activating phosphorylation events in the mitogen-activated protein kinase pathway and does not inhibit decay of IEG mRNAs. (sigmaaldrich.com)
  • 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. (wikipedia.org)
  • M cyclin concentrations rise as the cell begins to enter mitosis and the concentrations peak at metaphase. (wikipedia.org)
  • The destruction of M cyclins during metaphase and anaphase, after the Spindle Assembly Checkpoint is satisfied, causes the exit of mitosis and cytokinesis. (wikipedia.org)
  • Finally, cyclin B binds to CDK-1 to drive the cycle forward into M phase, stimulating mitosis. (news-medical.net)
  • Cyclin B1 is a regulatory protein involved in mitosis. (rockland-inc.com)
  • The D and E type cyclins regulate the passage of G1, while cyclin B is a critical regulator of mitosis. (fishersci.com)
  • 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. (thermofisher.com)
  • The cyclin concentration increases during the cycle until halfway to the mitosis stage, when it drops to zero. (thefreedictionary.com)
  • Cyclin may act as a molecular switch that activates mitosis when its concentration reaches a certain point. (thefreedictionary.com)
  • Low molecular weight cyclin E overexpression shortens mitosis, leading to chromosome missegregation and centrosome amplification. (semanticscholar.org)
  • During RG division, Cyclin D2 protein is asymmetrically distributed to two daughter cells following mitosis. (wiley.com)
  • 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. (embl.de)
  • G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). (embl.de)
  • 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. (medindia.net)
  • 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. (medindia.net)
  • 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. (medindia.net)
  • 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. (researchandmarkets.com)
  • 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. (researchandmarkets.com)
  • 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. (eurekalert.org)
  • In the current study, the group sought to investigate the mechanism by which cyclin D1 regulates the biogenesis of non coding miRNA. (eurekalert.org)
  • Finally, two results suggest that cyclin C regulates programmed cell death independently of its function as a transcriptional repressor. (genetics.org)
  • Unlike other cyclins that positively regulate the cell cycle, cyclin G2 (CCNG2) regulates cell proliferation as a tumor suppressor gene. (spandidos-publications.com)
  • Kaposi sarcoma herpesvirus ( KSHV ) encodes a D-type cyclin (ORF72) that binds CDK6 and is likely to contribute to KSHV-related cancers [9] . (wikipedia.org)
  • Initially, a mitogenic stimulus leads to the upregulation of cyclin D gene expression, which binds to CDK4. (news-medical.net)
  • It binds to cyclin-dependent kinase 8 (CDK8) and enhances its kinase activity. (sigmaaldrich.com)
  • In tumor cells, cyclin E is converted to low-molecular weight forms, an event that does not occur in normal cells. (scienceblog.com)
  • A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. (harvard.edu)
  • 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. (sigmaaldrich.com)
  • R-roscovitine inhibits human pituitary corticotroph tumor ACTH by targeting the cyclin E/E2F1 pathway. (sigmaaldrich.com)
  • These data indicated that the tumor-promoting activity of cyclin D1 may be tissue specific. (aacrjournals.org)
  • This supports results from earlier studies that suggest that cyclin D1 could be used as a prognostic biomarker. (fiercebiotech.com)
  • We suggest that cyclin B might be a potent prognostic factor in this low-risk patient group. (kb.se)
  • This cyclin and its kinase partner CDK9 were found to be subunits of the transcription elongation factor p-TEFb. (wikipedia.org)
  • Cyclin T2 has been shown to interact with CDK9 and Retinoblastoma protein. (wikipedia.org)
  • Cyclin K interacts with CDK12 and CDK13 but not CDK9 in cells, and is required to maintain self-renewal in ES cells. (antibodies-online.com)
  • Cyclin K inhibits HIV-1 gene expression and replication by interfering with cyclin-dependent kinase 9 (CDK9)-cyclin T1 interaction in Nef-dependent manner. (antibodies-online.com)
  • These results reveal an unexpectedly direct role for CDK9-cyclin K in checkpoint pathways that maintain genome integrity in response to replication stress. (antibodies-online.com)
  • P-TEFb containing cyclin K and Cdk9 can activate transcription via RNA. (antibodies-online.com)
  • The primary mechanism of CDK activation is binding to corresponding cyclins, including cyclin T1, which is the usual regulatory cofactor of CDK9. (mdpi.com)
  • HIV-1 Tat protein interacts with CDK9 and cyclin T, suggesting CDK9 may have a role in AIDS. (thefreedictionary.com)
  • 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. (thefreedictionary.com)
  • 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. (thefreedictionary.com)
  • Cyclin specificity: how many wheels do you need on a unicycle? (biomedsearch.com)
  • The sensitivity and specificity of cyclin B was 65% and 92%, respectively. (kb.se)
  • 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. (wikipedia.org)
  • 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. (nih.gov)
  • They did this by expressing the cell-cycle regulator, a protein called cyclin A2. (rxpgnews.com)
  • These results define both a new function for SNIP1 and identify a previously unrecognized regulator of the cell cycle and cyclin D1 expression. (nature.com)
  • Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. (curehunter.com)
  • Second, the human cyclin C, which does not repress transcription in yeast, does regulate ROS sensitivity. (genetics.org)
  • Cyclins positively regulate cell proliferation to a large extent. (spandidos-publications.com)
  • E type cyclins (E1 and E2) are believed to drive cell entry into the S phase. (uniprot.org)
  • It is widely assumed that the two E type cyclins are critically required for proliferation of all cell types. (uniprot.org)
  • Here, we demonstrate that E type cyclins are largely dispensable for mouse development. (uniprot.org)
  • 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. (uniprot.org)
  • 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. (nature.com)
  • CBP-S436A islets exhibited elevated cyclin A2, reduced p27, and no changes in D-type cyclins, PDX-1, or Skp2. (diabetesjournals.org)
  • C-, H- and J18 types only contain a cyclin-C domain, and U-type cyclins contain another potential cyclin domain. (mdpi.com)
  • NMB or NMBR silencing inhibited M-CSF (zeige CSF1R Proteine )/ c-Fms (zeige CSF1R Proteine )-mediated downstream signaling pathways like activation of ERK (zeige EPHB2 Proteine ) and Akt (zeige AKT1 Proteine ) and induction of D-type cyclins, cyclin D1 and D2. (antikoerper-online.de)
  • We show here that accumulation of the wild-type p53 protein in either human or murine cells markedly increases expression of cyclin D1. (aacrjournals.org)
  • 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. (antibodies-online.com)
  • 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. (kb.se)
  • 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. (wikipedia.org)
  • Expression of human cyclins through the cell cycle . (wikipedia.org)
  • Cyclins were originally named because their concentration varies in a cyclical fashion during the cell cycle. (wikipedia.org)
  • 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. (wikipedia.org)
  • [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. (wikipedia.org)
  • Cyclins can be divided into four classes based on their behavior in the cell cycle of vertebrate somatic cells and yeast cells: G1 cyclins, G1/S cyclins, S cyclins, and M cyclins. (wikipedia.org)
  • 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. (wikipedia.org)
  • The cyclins also promote other activities to progress the cell cycle, such as centrosome duplication in vertebrates or spindle pole body in yeast. (wikipedia.org)
  • 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. (wikipedia.org)
  • The presence of G cyclins coordinate cell growth with the entry to a new cell cycle. (wikipedia.org)
  • [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 . (wikipedia.org)
  • 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. (wikipedia.org)
  • Cyclins were originally discovered by R. Timothy Hunt in 1982 while studying the cell cycle of sea urchins. (wikipedia.org)
  • There are several different cyclins that are active in different parts of the cell cycle and that cause the Cdk to phosphorylate different substrates. (wikipedia.org)
  • CDC28 was identified in Saccharomyces cerevisiae , which bound to cyclins and drove the cell through the various transitions of the cell cycle. (news-medical.net)
  • Knockdown of Cyclin I induced cell cycle arrest at S/G2/M phases. (nih.gov)
  • Modulation of cyclin accumulation, and thereby Cdk activation, was proposed to be the overarching principle governing the passage through cell cycle phases. (springer.com)
  • 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. (uniprot.org)
  • 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. (eurekalert.org)
  • 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. (thefreedictionary.com)
  • Cyclin A1 transfected 293T cell line lysate. (abcam.com)
  • 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. (eurekalert.org)
  • The research, focused on the role of cyclin, one of the most important protein molecules needed for cell division. (eurekalert.org)
  • 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. (eurekalert.org)
  • 6-Gingerol induces cell-cycle G1-phase arrest through AKT-GSK 3β-cyclin D1 pathway in renal-cell carcinoma. (greenmedinfo.com)
  • Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. (addgene.org)
  • 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. (rxpgnews.com)
  • Cyclin A1 is also expressed in several myeloid leukemia cell lines and various other tumour types (Yang et al. (atlasgeneticsoncology.org)
  • 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. (atlasgeneticsoncology.org)
  • Male knockout mice lacking cyclin A1 are infertile owing to a cell cycle arrest before the first meiotic division (Liu et al. (atlasgeneticsoncology.org)
  • 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. (sciencemag.org)
  • 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). (diabetesjournals.org)
  • 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. (diabetesjournals.org)
  • Cyclins play important roles in cell division and cell expansion. (mdpi.com)
  • 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. (novusbio.com)
  • In addition to its role in regulating the cell cycle cyclin D1 induc. (bio-medicine.org)
  • However, this kit has a low detection level for cyclin D1 in some cell lines, such as HeLa, Mv 1 Lu or NIH/3T3. (cellsignal.com)
  • Cyclin D1 is unsuitable for minimal residual disease monitoring in bone marrow of patients with mantle cell lymphoma. (antikoerper-online.de)
  • 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. (antikoerper-online.de)
  • in its absence, cyclins D2 and D3 are also not expressed, preventing hematopoietic cell division and differentiation at its earliest stage. (antikoerper-online.de)
  • Induction of mammary gland hyperplasia and carcinomas in transgenic mice expressing human cyclin E. Mol Cell Biol. (springer.com)
  • Expression of cell cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients. (springer.com)
  • Cyclin-dependent kinase (CDK) activity is essential for eukaryotic cell cycle events. (biomedsearch.com)
  • Experimental data has suggested that cyclin D1 and E mediate cell proliferation by different mechanisms in estrogen receptor (ER) positive and negative breast cancer. (kb.se)
  • Cyclin B1 is overexpressed in various cancers, including breast, prostate, and non-small cell lung cancer. (thermofisher.com)
  • that cyclin K may be a novel molecular link between germ cell development, cancer development and embryonic stem cell maintenance. (antibodies-online.com)
  • 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. (atlasgeneticsoncology.org)
  • The distribution patterns of pUL97 and cyclin T1 were independent of HCMV strain and host cell type. (mdpi.com)
  • 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. (sigmaaldrich.com)
  • These findings demonstrate a new role for the Slt2p MAP kinase cascade in protecting the cell from programmed cell death through cyclin C destruction. (genetics.org)
  • Several prostate cancer cell lines and a subset of primary prostate cancer samples have increased cyclin D1 protein expression. (aacrjournals.org)
  • 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 . (aacrjournals.org)
  • Studies have shown that mouse prostatic normal and Rb −/− epithelial cells have elevated cyclin D1 expression as they enter the cell cycle ( 18 ). (aacrjournals.org)
  • 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. (wiley.com)
  • The daughter cell that inherits Cyclin D2 mRNA maintains its self-renewal capability, while its sibling undergoes differentiation. (wiley.com)
  • 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. (wiley.com)
  • 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. (wiley.com)
  • Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (wikipedia.org)
  • 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. (pnas.org)
  • 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. (pnas.org)
  • Diverse mitotic events can be triggered in the correct order and time by a single cyclin-CDK. (nih.gov)
  • 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. (nih.gov)
  • We conclude that mitotic events are regulated by discrete cyclin-CDK thresholds. (nih.gov)
  • G2/mitotic-specific cyclin-B2, HsT17299, cyclin B2. (prospecbio.com)
  • 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. (nih.gov)
  • 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. (sciencemag.org)
  • 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. (nature.com)
  • PDX-1 knockdown reduced exendin-4-stimulated cAMP synthesis and cyclin A2 transcription. (diabetesjournals.org)
  • Human cdk8-cyclin C might be functionally associated with the mammalian transcription apparatus, perhaps involved in relaying growth-regulatory signals. (novusbio.com)
  • I have been defining the cis -acting elements and trans -acting factors that control transcription of the human cyclin D3 gene in T-cells. (bl.uk)
  • The minimal cyclin D3 promoter sequence was identified as a region 173bp upstream of the transcription initiation site. (bl.uk)
  • The protein encoded by CCNK is a member of the transcription cyclin family. (antibodies-online.com)
  • Retroviral cyclin controls cyclin-dependent kinase 8-mediated transcription elongation and reinitiation. (sigmaaldrich.com)
  • Previous work showed that the retroviral cyclin (RV-cyclin), encoded by WDSV, has separable cyclin box and transcription activation domains. (sigmaaldrich.com)
  • 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. (sigmaaldrich.com)
  • 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. (atlasgeneticsoncology.org)
  • 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. (antibodies-online.com)
  • Cyclin E-Mediated Human Proopiomelanocortin Regulation as a Therapeutic Target for Cushing Disease. (sigmaaldrich.com)
  • Cyclin E and E2F1 exhibit reciprocal positive regulation in corticotroph tumors. (sigmaaldrich.com)
  • Alvocidib is an investigational small molecule inhibitor of cyclin-dependent kinase 9 , a protein important to the regulation of Myc. (thefreedictionary.com)
  • Microarray analysis showed that the expression profiles between CAFs and NPF cyclin D1 cells were highly concordant including cyclin D1 up-regulation. (aacrjournals.org)
  • However, all members of the cyclin family are similar in 100 amino acids that make up the cyclin box. (wikipedia.org)
  • 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. (atlasgeneticsoncology.org)
  • In contrast to mammalian cells, these yeast cells had only one CDK which interacted with various cyclins. (news-medical.net)
  • Mammalian cyclin A1 is primarily localized in the nuclei of spermatocytes in mouse and human (Liu et al. (atlasgeneticsoncology.org)
  • In mammalian somatic cells, cyclin A is required for S-phase and passage through G2-phase. (fishersci.com)
  • Cyclin K is highly expressed in mammalian testes in a developmentally regulated manner. (antibodies-online.com)
  • Here, we discuss our findings and the Cyclin D2 function in mammalian brain development and evolution. (wiley.com)
  • Cyclin-dependent kinase 6 (CDK6) bound to the inhibitor ribociclib (detail view). (news-medical.net)
  • Verzenio is a cyclin-dependent kinase (CDK)4 & 6 inhibitor that will be available as 50, 100, 150 and 200 mg tablets. (thefreedictionary.com)
  • 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 . (scienceblog.com)
  • 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. (scienceblog.com)
  • This arrest is characterized by accumulation of the cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) and of underphosphorylated forms of retinoblastoma protein. (aacrjournals.org)
  • Cardiac differentiation in Xenopus requires the cyclin-dependent kinase inhibitor, p27Xic1. (biomedsearch.com)
  • Belongs to the cdkn2 cyclin-dependent kinase inhibitor family. (atlasgeneticsoncology.org)
  • Cyclin-Dependent Kinase Inhibitor p21" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
  • 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. (harvard.edu)
  • Below are the most recent publications written about "Cyclin-Dependent Kinase Inhibitor p21" by people in Profiles. (harvard.edu)
  • Cyclin A2 overexpression in primary islets increased proliferation and reduced p27. (diabetesjournals.org)
  • In Min6 cells, cyclin A2 knockdown prevented exendin-4-stimulated proliferation. (diabetesjournals.org)
  • 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. (kb.se)
  • 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. (news-medical.net)
  • Overexpression of cyclin D1 reduced STAT3-dependent gene expression in a dose-dependent manner. (sciencemag.org)
  • 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. (sigmaaldrich.com)
  • Donnellan R, Kleinschmidt I, Chetty R. Cyclin E immunoexpression in breast ductal carcinoma: pathologic correlations and prognostic implications. (springer.com)
  • We wanted to examine cyclin B as a prognostic factor in low-risk breast cancer patients. (kb.se)
  • 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. (sigmaaldrich.com)
  • 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. (wiley.com)
  • S cyclins bind to Cdk and the complex directly induces DNA replication. (wikipedia.org)
  • 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. (wikipedia.org)
  • Confocal immunofluorescence revealed partial colocalization of pUL97 with cyclin T1 in subnuclear compartments, most pronounced in viral replication centres. (mdpi.com)
  • 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. (scienceblog.com)
  • 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. (aacrjournals.org)
  • Overexpression of cyclin D1 plays important roles in the development of human cancers, including breast, colon, and melanoma ( 11 , 13 - 17 ). (aacrjournals.org)
  • 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. (eurekalert.org)
  • Background: Cyclin D1 gene (CCND1) plays pivotal roles in the development of several human cancers, including breast cancer, functioning as an oncogene. (hindawi.com)
  • A second prediction of the model is that increasing the rate of cyclin accumulation should globally advance timing of all events. (nih.gov)
  • Cyclins are generally very different from each other in primary structure, or amino acid sequence. (wikipedia.org)
  • Cyclins exhibit diverse sequences but all share homology over a region of approximately 100 amino acids, termed the cyclin box. (nih.gov)
  • 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. (bio.net)
  • It recognizes a protein of 54kDa, which is identified as cyclin A. Its epitope is located amino acids 144-148 of human Cyclin A2. (fishersci.com)
  • The sequence domain of pUL97 responsible for the interaction with cyclin T1 was between amino acids 231-280. (mdpi.com)
  • We have solved the crystal structure, at 2.0 A resolution, of an active recombinant fragment of bovine cyclin A, cyclin A-3, corresponding to residues 171-432 of human cyclin A. The cyclin box has an alpha-helical fold comprising five alpha helices. (nih.gov)
  • Recombinant human Cyclin E1 protein, around 100-200aa. (thermofisher.com)
  • Recombinant protein encompassing a sequence within the center region of human Cyclin B1. (genetex.com)
  • 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. (scienceblog.com)
  • Of those, 100 expressed normal levels of wild-type cyclin E, and 28 overexpressed the low forms," Keyomarsi said. (scienceblog.com)
  • 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. (scienceblog.com)
  • 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. (mdpi.com)
  • Exendin-4 stimulated cyclin A2 promoter activity via the cAMP-cAMP response element binding protein pathway. (diabetesjournals.org)
  • The human cyclin D3 gene has a TATA-less promoter and a single dominant initiation site. (bl.uk)
  • Transient transfections using CAT (chloramphenicol acetyltransferase) reporter constructs containing sequential deletions of the cyclin D3 promoter defined positively and negatively regulated regions. (bl.uk)
  • 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. (antibodies-online.com)