Cyclin dependent kinases. Medical search

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 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.

Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.

A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.

A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.

A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.

Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.

A 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.

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.

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 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 serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.

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 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 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.

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 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.

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.

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 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.

A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.

A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.

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.

The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.

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.

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.

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.

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.

Agents that inhibit PROTEIN KINASES.

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.

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 family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.

All of the processes involved in increasing CELL NUMBER including CELL DIVISION.

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.

The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.

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.

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.

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 widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.

Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.

A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.

A cell line derived from cultured tumor cells.

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 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.

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.

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.

An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.

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.

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.

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.

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.

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 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 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 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.

A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

Nuclear 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.

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.

Established cell cultures that have the potential to propagate indefinitely.

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.

Transport proteins that carry specific substances in the blood or across cell membranes.

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.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

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.

An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.

Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.

A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

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.

Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.

Substances that inhibit or prevent the proliferation of NEOPLASMS.

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.

A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.

A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.

A cyclin B subtype that colocalizes with GOLGI APPARATUS during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.

A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.

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.

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.

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.

The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.

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 serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.

A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.

A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.

A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.

Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.

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.

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.

The rate dynamics in chemical or physical systems.

A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.

Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).

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.

Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.

A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.

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 basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.

A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.

A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.

Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

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 family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.

A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).

An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.

Elements of limited time intervals, contributing to particular results or situations.

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.

A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.

A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.

A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.

ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.

A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.

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.

DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.

A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.

Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.

An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.

A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.

A group of phenyl benzopyrans named for having structures like FLAVONES.

Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.

Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.

A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.

A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.

A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.

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.

Proteins prepared by recombinant DNA technology.

The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.

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.

An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.

A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.

A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.

A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.

The process by which a DNA molecule is duplicated.

The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.

Cell regulatory signaling system that controls progression through S PHASE and stabilizes the replication forks during conditions that could affect the fidelity of DNA REPLICATION, such as DNA DAMAGE or depletion of nucleotide pools.

A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.

A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.

A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.

A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.

Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.

Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).

Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.

Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.

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.

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.

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 non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.

The relationship between the dose of an administered drug and the response of the organism to the drug.

The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.

Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.

A 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.

A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.

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.

Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.

A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.

A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.

An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.

A family of non-receptor, PROLINE-rich protein-tyrosine kinases.

A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.

A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.

The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.

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.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.

A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.

An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.

A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.

Derivatives of the steroid androstane having two double bonds at any site in any of the rings.

A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.

The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.

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.

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.

Tumors or cancer of the human BREAST.

PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.

Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.

A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.

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.

The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.

Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.

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).

An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.

A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes

A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)

Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.

The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.

Tumor suppressor genes located on human chromosome 9 in the region 9p21. This gene is either deleted or mutated in a wide range of malignancies. (From Segen, Current Med Talk, 1995) Two alternatively spliced gene products are encoded by p16: CYCLIN-DEPENDENT KINASE INHIBITOR P16 and TUMOR SUPPRESSOR PROTEIN P14ARF.

A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.

Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.

An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3.

A casein kinase that was originally described as a monomeric enzyme with a molecular weight of 30-40 kDa. Several ISOENZYMES of casein kinase I have been found which are encoded by separate genes. Many of the casein kinase I isoenzymes have been shown to play distinctive roles in intracellular SIGNAL TRANSDUCTION.

Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.

A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.

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.

Activation of telomerase and its association with G1-phase of the cell cycle during UVB-induced skin tumorigenesis in SKH-1 hairless mouse. (1/4016)

Telomerase is a ribonucleoprotein enzyme that adds hexanucleotide repeats TTAGGG to the ends of chromosomes. Telomerase activation is known to play a crucial role in cell-immortalization and carcinogenesis. Telomerase is shown to have a correlation with cell cycle progression, which is controlled by the regulation of cyclins, cyclin dependent kinases (cdks) and cyclin dependent kinase inhibitors (cdkis). Abnormal expression of these regulatory molecules may cause alterations in cell cycle with uncontrolled cell growth, a universal feature of neoplasia. Skin cancer is the most prevalent form of cancer in humans and the solar UV radiation is its major cause. Here, we investigated modulation in telomerase activity and protein expression of cell cycle regulatory molecules during the development of UVB-induced tumors in SKH-1 hairless mice. The mice were exposed to 180 mjoules/cm2 UVB radiation, thrice weekly for 24 weeks. The animals were sacrificed at 4 week intervals and the studies were performed in epidermis. Telomerase activity was barely detectable in the epidermis of non-irradiated mouse. UVB exposure resulted in a progressive increase in telomerase activity starting from the 4th week of exposure. The increased telomerase activity either persisted or further increased with the increased exposure. In papillomas and carcinomas the enzyme activity was comparable and was 45-fold higher than in the epidermis of control mice. Western blot analysis showed an upregulation in the protein expression of cyclin D1 and cyclin E and their regulatory subunits cdk4 and cdk2 during the course of UVB exposure and in papillomas and carcinomas. The protein expression of cdk6 and ckis viz. p16/Ink4A, p21/Waf1 and p27/Kip1 did not show any significant change in UVB exposed skin, but significant upregulation was observed both in papillomas and carcinomas. The results suggest that telomerase activation may be involved in UVB-induced tumorigenesis in mouse skin and that increased telomerase activity may be associated with G1 phase of the cell cycle. (+info)

Comparative molecular genetic profiles of anaplastic astrocytomas/glioblastomas multiforme and their subsequent recurrences. (2/4016)

Malignant glial tumors (anaplastic astrocytomas and glioblastomas multiforme) arise mostly either from the progression of low grade precursor lesions or rapidly in a de novo fashion and contain distinct genetic alterations. There is, however, a third subset of malignant gliomas in which genetic lesions remain to be identified. Following surgical resection, all gliomas appear to have an inherent tendency to recur. Comparative molecular analysis of ten primary malignant gliomas (three anaplastic astrocytomas and seven glioblastomas multiforme) with their recurrences identified two distinct subgroups of recurrent tumors. In one group, primary tumors harbored genetic aberrations frequently associated with linear progression or de novo formation pathways of glial tumorigenesis and maintained their genetic profiles upon recurrence. In the other subset with no detectable known genetic mutations at first presentation, the recurrent tumors sustained specific abnormalities associated with pathways of linear progression or de novo formation. These included loss of genes on chromosomes 17 and 10, mutations in the p53 gene, homozygous deletion of the DMBTA1 and p16 and/ or p15 genes and amplification and/or overexpression of CDK4 and alpha form of the PDGF receptor. Recurrent tumors from both groups also displayed an abnormal expression profile of the metalloproteinase, gel A, and its inhibitor, TIMP-2, consistent with their highly invasive behavior. Delineation of the molecular differences between malignant glioblastomas and their subsequent recurrences may have important implications for the development of rational clinical approaches for this neoplasm that remains refractory to existing therapeutic modalities. (+info)

The role of RBF in the introduction of G1 regulation during Drosophila embryogenesis. (3/4016)

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)

Coupling of the cell cycle and myogenesis through the cyclin D1-dependent interaction of MyoD with cdk4. (4/4016)

Proliferating myoblasts express the muscle determination factor, MyoD, throughout the cell cycle in the absence of differentiation. Here we show that a mitogen-sensitive mechanism, involving the direct interaction between MyoD and cdk4, restricts myoblast differentiation to cells that have entered into the G0 phase of the cell cycle under mitogen withdrawal. Interaction between MyoD and cdk4 disrupts MyoD DNA-binding, muscle-specific gene activation and myogenic conversion of 10T1/2 cells independently of cyclin D1 and the CAK activation of cdk4. Forced induction of cyclin D1 in myotubes results in the cytoplasmic to nuclear translocation of cdk4. The specific MyoD-cdk4 interaction in dividing myoblasts, coupled with the cyclin D1-dependent nuclear targeting of cdk4, suggests a mitogen-sensitive mechanism whereby cyclin D1 can regulate MyoD function and the onset of myogenesis by controlling the cellular location of cdk4 rather than the phosphorylation status of MyoD. (+info)

Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. (5/4016)

The D-type cyclins and their major kinase partners CDK4 and CDK6 regulate G0-G1-S progression by contributing to the phosphorylation and inactivation of the retinoblastoma gene product, pRB. Assembly of active cyclin D-CDK complexes in response to mitogenic signals is negatively regulated by INK4 family members. Here we show that although all four INK4 proteins associate with CDK4 and CDK6 in vitro, only p16(INK4a) can form stable, binary complexes with both CDK4 and CDK6 in proliferating cells. The other INK4 family members form stable complexes with CDK6 but associate only transiently with CDK4. Conversely, CDK4 stably associates with both p21(CIP1) and p27(KIP1) in cyclin-containing complexes, suggesting that CDK4 is in equilibrium between INK4 and p21(CIP1)- or p27(KIP1)-bound states. In agreement with this hypothesis, overexpression of p21(CIP1) in 293 cells, where CDK4 is bound to p16(INK4a), stimulates the formation of ternary cyclin D-CDK4-p21(CIP1) complexes. These data suggest that members of the p21 family of proteins promote the association of D-type cyclins with CDKs by counteracting the effects of INK4 molecules. (+info)

Induced expression of p16(INK4a) inhibits both CDK4- and CDK2-associated kinase activity by reassortment of cyclin-CDK-inhibitor complexes. (6/4016)

To investigate the mode of action of the p16(INK4a) tumor suppressor protein, we have established U2-OS cells in which the expression of p16(INK4a) can be regulated by addition or removal of isopropyl-beta-D-thiogalactopyranoside. As expected, induction of p16(INK4a) results in a G1 cell cycle arrest by inhibiting phosphorylation of the retinoblastoma protein (pRb) by the cyclin-dependent kinases CDK4 and CDK6. However, induction of p16(INK4a) also causes marked inhibition of CDK2 activity. In the case of cyclin E-CDK2, this is brought about by reassortment of cyclin, CDK, and CDK-inhibitor complexes, particularly those involving p27(KIP1). Size fractionation of the cellular lysates reveals that a substantial proportion of CDK4 participates in active kinase complexes of around 200 kDa. Upon induction of p16(INK4a), this complex is partly dissociated, and the majority of CDK4 is found in lower-molecular-weight fractions consistent with the formation of a binary complex with p16(INK4a). Sequestration of CDK4 by p16(INK4a) allows cyclin D1 to associate increasingly with CDK2, without affecting its interactions with the CIP/KIP inhibitors. Thus, upon the induction of p16(INK4a), p27(KIP1) appears to switch its allegiance from CDK4 to CDK2, and the accompanying reassortment of components leads to the inhibition of cyclin E-CDK2 by p27(KIP1) and p21(CIP1). Significantly, p16(INK4a) itself does not appear to form higher-order complexes, and the overwhelming majority remains either free or forms binary associations with CDK4 and CDK6. (+info)

Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (7/4016)

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. (8/4016)

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)

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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)
In plants, different families of cyclin-dependent kinases (CDKs) and cyclins have been identified, indicating that also in plants the progression through the cell cycle is regulated by CDKs. (nih.gov)
Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. (wikipedia.org)
CDKs are relatively small proteins, with molecular weights ranging from 34 to 40 kDa, and contain little more than the kinase domain. (wikipedia.org)
CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases. (wikipedia.org)
The structure of human Cdk2 revealed that CDKs have a modified ATP-binding site that can be regulated by cyclin binding. (wikipedia.org)
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)
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)
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)
However, due to the high degree of structural homology within the CDK protein family, putative small-molecule CDK inhibitors may exert their effects through combinatorial inhibition of multiple CDKs and other closely related serine/threonine kinases. (aacrjournals.org)
Cyclin-dependent kinases (CDKs) have been considered promising drug targets for a number of years, but most CDK inhibitors have failed rigorous clinical testing. (aspetjournals.org)
Therefore, there is an urgent need for new cancer-targeted drugs, which has led (inter alia) to the development of molecules that can specifically inhibit cyclin-dependent kinases (CDKs). (eurekaselect.com)
Clinical resistance to CDK inhibitors has not yet been described, but by comparing CDKs to other kinases, and CDK inhibitors to other clinically used protein kinase inhibitors, we also discuss possible mechanisms that could lead to resistance to CDK inhibitors. (eurekaselect.com)
Here, we show that a pyrazolo[1,5- a ]pyrimidine-derived compound, BS-181, inhibited CAK activity with an IC 50 of 21 nmol/L. Testing of other CDKs as well as another 69 kinases showed that BS-181 only inhibited CDK2 at concentrations lower than 1 μmol/L, with CDK2 being inhibited 35-fold less potently (IC 50 880 nmol/L) than CDK7. (aacrjournals.org)
Drugs targeting the cell cycle-regulatory cyclin-dependent kinase (CDK) 4 and 6 have been approved for the treatment of hormone receptor-positive breast cancer, and inhibitors targeting other cell-cycle CDKs are currently in clinical trials. (aacrjournals.org)
In mammalian cells, cell cycle traversal is regulated by cyclins and cyclin-dependent kinases (CDKs) that are in turn controlled by CDK inhibitors (CKIs) ( 31 ). (asm.org)
Cyclin-dependent kinases (CDKs) are required for initiation of DNA replication in all eukaryotes, and appear to act at multiple levels to control replication origin firing, depending on the cell type and stage of development. (inserm.fr)
Deregulation of cyclin-dependent kinases (CDKs) has been associated with many cancer types and has evoked an interest in chemical inhibitors with possible therapeutic benefit. (eurekaselect.com)
Requirement for the cyclin dependent kinase (CDK) inhibitor p21 downstream of p53 suggests a pivotal role for CDKs in controlling IE gene repression in S/G2 and treatment of S/G2 cells with the CDK inhibitor roscovitine alleviates IE repression independently of p53. (prolekare.cz)
CDKs are attractive targets for drug development, given that certain malignancies are dependent on dysregulated cyclin activity ( 1 ) and CDK inhibition has been observed as a potent vehicle to overcome resistance to standard chemotherapy ( 2-4 ). (aacrjournals.org)
Progression through the G1, S, G2 and M phases of the cell cycle is controlled by cyclin-dependent kinases (Cdks) and cyclins. (diva-portal.org)
The eight cyclin-dependent protein kinases (Cdks) that have been identified to date play an essential role in the regulation of the cell cycle. (merckmillipore.com)
For example, the G1/S transition is regulated by Cdk2/cyclin E, Cdk3/unknown cyclin, Cdk4/cyclin D1-3, Cdk6/cyclin D1, and Cdk8/cyclin C. The frequent deregulation of Cdks and their regulators in cancer has stimulated the search for potent and selective inhibitors of Cdks for both research and therapeutic use. (merckmillipore.com)
Extracts from a diverse collection of cell types and organisms were screened for proteins binding purvalanol B. In addition to validating CDKs as intracellular targets, a variety of unexpected protein kinases were recovered from the 95 matrix. (lancs.ac.uk)
Cell cycle progression is controlled by several cyclin-dependent kinases (CDKs) that associate with regulatory cyclins. (ahajournals.org)
Interaction of CDKs/cyclins with CDK inhibitory proteins (CKIs) attenuates CDK activity and promotes growth arrest. (ahajournals.org)
5 CKIs of the Cip/Kip family (p21 Cip1 , p27 Kip1 , and p57 Kip2 ) bind to and inhibit a wide spectrum of CDK/cyclin holoenzymes, whereas members of the Ink4 family (p16 Ink4a , p15 Ink4b , p18 Ink4c , and p19 Ink4d ) are specific for cyclin D-associated CDKs. (ahajournals.org)

Cyclin A is also produced, which binds to CDK2 and stimulates DNA replication. (news-medical.net)
Where examined, both Cdc2 and Cdk2, the catalytic subunits known to associate with cyclin A, were activated. (pnas.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)
By inhibiting cyclin D and c-Myc, trastuzumab releases the sequestrated p27bKip1 protein from cyclin D-CDK4/6 complexes and increase the effect of p27Kip1 on CDK2-cyclin E complexes. (nih.gov)
By stimulating minibrain related kinase (MIRK), trastuzumab stabilizes p27Kip1 in the nucleus, which increases inhibitory action of p27Kip1 on CDK2. (nih.gov)
CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. (researchandmarkets.com)
This G1 arrest is associated with a dramatic decrease in the protein levels of Cdk2 and cyclin E correlated with an inhibition of the Cdk2 kinase activity. (biomedsearch.com)
CDK2 and CDK1 are two closely related kinases that play overlapping roles during cell division, contributing to the phosphorylation and inactivation of the retinoblastoma (Rb) tumor suppressor gene product throughout late G 1 , S, and G 2 -M phases ( 5 - 7 ). (aacrjournals.org)
Consistent with a key role for CDK6 as a D-cyclin partner in thymocytes, knockout (KO) of CDK4 or CDK2 was shown to have no significant effect on T-cell development ( 11 , 12 ), but significantly decreased thymic cellularity was observed in a CDK6 KO animal ( 13 ). (aacrjournals.org)
Normal progression through the cell cycle requires the sequential action of cyclin-dependent kinases CDK1, CDK2, CDK4, and CDK6. (aacrjournals.org)
The CDK-activating kinase (CAK) plays a critical role in regulating cell cycle by mediating the activating phosphorylation of CDK1, CDK2, CDK4, and CDK6. (aacrjournals.org)
p16 Ink4 inhibited cdk4, but not cdk2, kinase activity, producing partial inhibition of VSMC growth in vitro. (ahajournals.org)
Progression through G 1 and entry into the S phase is regulated by the formation and activation of cyclin/cyclin-dependent kinase (CDK) complexes, predominantly cyclin D-cdk4/6 and cyclin E-cdk2. (ahajournals.org)
Taking its origin from of OTAVA s in-house collection of 500,000 compounds, this CDK2 focused library is composed of 1281 compounds which were selected by computational estimation of their interaction with one specific member in a protein kinase family (sharp-focusing approach). (hum-molgen.org)
To address this apparent paradox, we examined possible predictors of the sensitivity of 10 breast cancer cell lines to erlotinib in light of cyclin-dependent kinase 2 (CDK2), considered the farthest downstream kinase that controls cell cycling in the EGFR signaling pathway. (pubmedcentralcanada.ca)
Reports that cell lines showing sensitivity to EGFR-TKIs showed G 1 arrest after treatment with EGFR-TKIs ( 11 - 13 ) led us to study the potential relationship between cyclin-dependent kinases (CDK), particularly CDK2 ( 12 , 13 ) and erlotinib sensitivity. (pubmedcentralcanada.ca)
CDK2 regulates the G 1 -S phase transition and, within the EGFR signaling pathway, is the farthest downstream molecule with known kinase activity ( 13 - 15 ). (pubmedcentralcanada.ca)
These cyclin-CDK complexes, as well as cyclin E-CDK2 complexes later in the cell cycle, phosphorylate retinoblastoma protein (Rb). (asm.org)
We identified that Thr85 immediately prior to the NLS of PTHrP was phosphorylated by CDC2-CDK2 and phosphorylation was cell cycle-dependent. (garvan.org.au)
Cdk2 was also phophorylated by this mytl kinase less than was done by the weel kinase. (nii.ac.jp)
Publications] Ohkubo,Y.: 'SV40 large T antigen reinduces the cell cyc10 in terminally differentiated myotubes through inducing cdk2, cdc 2 and their partner cyclins' Exptl. (nii.ac.jp)
5 For example, p27 Kip1 promotes the assembly of CDK4/cyclin D complexes, thus facilitating CDK2/cyclin E activation through the G 1 /S phase. (ahajournals.org)
This protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. (creativebiomart.net)

Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. (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)
only the cyclin-CDK complex is an active kinase but its activity can be typically further modulated by phosphorylation and other binding proteins, like p27. (wikipedia.org)
Substrate specificity of S cyclins is imparted by the hydrophobic batch (centered on the MRAIL sequence), which has affinity for substrate proteins that contain a hydrophobic RXL (or Cy) motif. (wikipedia.org)
Cdk1-cyclin complexes are also governed by direct binding of Cdk inhibitor proteins (CKIs). (wikipedia.org)
The activity of CDK6 is very tightly controlled by association with D-cyclins ( 7 ) and two families of CDK inhibitors, including the CIP/KIP family and the inhibitors of CDK4 (INK4) family proteins ( 9 ). (aacrjournals.org)
Here we demonstrate that the budding yeast cyclin-dependent kinase Cdc28 directly regulates the formation of the DNA double-strand breaks that initiate recombination by phosphorylating the Mer2/Rec107 protein and thereby modulating interactions of Mer2 with other proteins required for break formation. (pubmedcentralcanada.ca)
This DNA damage is dependent on CDK1 and -2 as well as the replication proteins MCM2 and CDT1 but not CDC25A. (rupress.org)
The initial response to replicative stress is activated mainly by the ATR (ataxia telangiectasia and Rad3-related protein) kinase, which targets proteins such as p53, H2AX, and the CHK1 kinase. (rupress.org)
Cyclin-CDK complex gets activated after phosphorylation which results in release of proteins, that leads to cell proliferation. (psmarketresearch.com)
CDK inhibitors are the proteins that networks with a cyclin-CDK complex to inhibit the kinase activity of the complex, usually during G1 phase. (psmarketresearch.com)
The PLSTIRE protein (cyclin-dependent kinase 6 (cdk6)), which shares extensive sequence homology (approximately 70%) with cdk4, was identified as the earliest inducible member of the cdk family of proteins in human T lymphocytes induced to proliferate in vitro by stimulation either with phorbol 12,13-dibutyrate and ionomycin (PDB/I) or PHA. (jimmunol.org)
The cyclin-dependent kinase inhibitor flavopiridol has antitumor activity against hematopoietic malignancies, including CLL, in which induction of apoptosis was associated with reduced expression of antiapoptotic proteins. (aacrjournals.org)
Cyclin-dependent kinases (CDK) are serine/threonine kinases that are activated upon association with cyclin proteins to form CDK complexes. (aacrjournals.org)
These proteins form active Cdk:cyclin complexes that phosphorylate specific substrates. (diva-portal.org)
We have implemented this approach into a protein-protein interaction analysis pipeline to differentiate between bona fide interaction partners of the low-level expressing cell cycle regulator cyclin-dependent kinase 9 (Cdk9) and nonspecifically binding or background proteins. (eur.nl)
To identify proteins which bind to mouse weel kinase, the yeast ' two-hybrid'system was used with a mouse cDNA library. (nii.ac.jp)
3 Mitogenic stimuli activate CDK/cyclin holoenzymes, thus causing hyperphosphorylation of the retinoblastoma protein (pRb) and related "pocket" proteins from mid G 1 to mitosis. (ahajournals.org)
Moreover, the proto-oncogene c- myc plays a key role in p27 sequestration through modulation of the level of cyclin D and E proteins. (ahajournals.org)
The Pho85 kinase shows genetic interactions with genes encoding proteins involved in cell polarity such as Cdc42, its regulators (i.e. (biologists.org)
CDKN1B, also known as cyclin-dependent kinase inhibitor 1B, belongs to the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitor proteins. (creativebiomart.net)

Cyclin-dependent kinase 6 (CDK6) bound to the inhibitor ribociclib (detail view). (news-medical.net)
Cyclin-dependent kinase 6 (CDK6) promotes cell cycle progression and is overexpressed in human lymphoid malignancies. (aacrjournals.org)
Using the OP9-DL1 system to deliver temporally controlled Notch receptor-dependent signaling, we show that CDK6 is required for Notch-dependent survival, proliferation, and differentiation. (aacrjournals.org)
These results show a critical requirement for CDK6 in Notch/Akt-dependent T-cell development and tumorigenesis and strongly support CDK6 as a specific therapeutic target in human lymphoid malignancies. (aacrjournals.org)
Cyclin-dependent kinase 6 (CDK6), a cyclin D-responsive regulator of the retinoblastoma protein (pRB) pathway, seems to be of central importance in T-cell development. (aacrjournals.org)
In contrast, cyclin D2 expression is high in the DN1-DN3 stages before pre-TCR assembly and barely detectable after pre-TCR assembly ( 10 ), suggesting that CDK6 may use different cyclin partners in the thymocyte developmental stages. (aacrjournals.org)
p15 interacts strongly with cyclin-dependent kinases CDK4 and CDK6, and inhibits their ability to interact with cyclins D, thereby blocking the CyclinD/CDK complex from phosphorylating the retinobloastoma protein (RB1). (cags.org.ae)
Regulation of synthesis and activity of the PLSTIRE protein (cyclin-dependent kinase 6 (cdk6)), a major cyclin D-associated cdk4 homologue in normal human T lymphocytes. (jimmunol.org)
Furthermore, increased accumulation of p40cdk6 protein and activity occurred in cells rendered "competent" (responsive to IL-2) by a brief treatment with PDB/I. Thus, increased accumulation of the protein and its activity begin before IL-2/IL-2 receptor interaction, suggesting that the cdk6-cyclin D2 complex might be involved in acquisition of the competent state in human T lymphocytes. (jimmunol.org)
Antigen receptor signaling or exposure to growth factors triggers de novo synthesis of D-type cyclins, which then associate with their catalytic partners CDK4 or CDK6. (asm.org)
p16 Ink4a , p15 Ink4b , p18 Ink4c and p19 Ink4d , and they bind specifically to Cdk4 and Cdk6, thereby negatively regulating their kinase activities and cell cycle progression. (diva-portal.org)

In mammalian cells, CDK1, with its partners cyclin A2 and B1, alone can drive the cell cycle. (wikipedia.org)
Cyclin B1 and B2 can localize Cdk1 to the nucleus and the Golgi, respectively, through a localization sequence outside the CDK-binding region. (wikipedia.org)
Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine kinase, and is a key player in cell cycle regulation. (wikipedia.org)
Cdk1 is comprised mostly by the bare protein kinase motif, which other protein kinases share. (wikipedia.org)
Cdk1, like other kinases, contains a cleft in which ATP fits. (wikipedia.org)
In addition to this catalytic core, Cdk1, like other cyclin-dependent kinases, contains a T-loop, which, in the absence of an interacting cyclin, prevents substrate binding to the Cdk1 active site. (wikipedia.org)
Cdk1 also contains a PSTAIRE helix, which, upon cyclin binding, moves and rearranges the active site, facilitating Cdk1 kinase activities. (wikipedia.org)
When bound to its cyclin partners, Cdk1 phosphorylation leads to cell cycle progression. (wikipedia.org)
however, when phosphorylated by Cln3-Cdk1, Whi5 is ejected from the nucleus, allowing for transcription of the G1/S regulon, which includes the G1/S cyclins Cln1,2. (wikipedia.org)
G1/S cyclin-Cdk1 activity leads to preparation for S phase entry (e.g., duplication of centromeres or the spindle pole body), and a rise in the S cyclins (Clb5,6 in S. cerevisiae). (wikipedia.org)
Cdk1 phosphorylation also leads to the activation of the ubiquitin-protein ligase APCCdc20, an activation which allows for chromatid segregation and, furthermore, degradation of M-phase cyclins. (wikipedia.org)
Most obviously, Cdk1 is regulated by its binding with its cyclin partners. (wikipedia.org)
furthermore, cyclins impart specificity to Cdk1 activity. (wikipedia.org)
Furthermore, cyclins can target Cdk1 to particular subcellular locations. (wikipedia.org)
In addition to regulation by cyclins, Cdk1 is regulated by phosphorylation. (wikipedia.org)
Both kinases are important negative regulators of CDK1 and -2. (rupress.org)
Furthermore, MCF-7 cells treated with IV-2 showed increased Cdk1 kinase activity and a decrease in Cdk1 tyrosine phosphorylation, indicating that IV-2 did not directly inhibit Cdk1 or Cdc25 activities. (aspetjournals.org)
Cyclin-afhængig kinase 1 (Cdk1) er aktiveret i G2 fase af cellecyklus og regulerer mange cellulære veje. (jove.com)
Her præsenterer vi en protokol for en in vitro- kinase assay med Cdk1, som giver mulighed for identifikation af Cdk1-specifikke fosforylering websteder til oprettelse af cellulære mål for denne vigtige kinase. (jove.com)
Her, beskriver vi en in vitro- kinase assay, der bruges til at identificere Cdk1-specifikke fosforylering websteder. (jove.com)
I denne analyse, et oprenset protein er fosforyleres i vitro af kommercielt tilgængelige menneskelige Cdk1/cyclin B. vellykket fosforylering er bekræftet af SDS-PAGE og fosforylering websteder er efterfølgende identificeret ved massespektrometri. (jove.com)
Sammen præsentere disse protokoller en meget kraftfuld tilgang, der giver Cdk1-specifikke fosforylering websteder og muliggør Mekanistiske undersøgelser i hvordan Cdk1 kontrol af cellecyklus. (jove.com)
Cdk1, som er også kendt som celledeling cyklus protein 2 homolog (cdc2) er en master controller til cellecyklus i alle eukaryoter 1 , 2 , 3 , 4 , 5 , og phosphorylates en anslåede 8-13% af proteomet 6 , 7 . (jove.com)
I denne analyse, er kommercielt tilgængelige menneskelige Cdk1/cyclin B bruges til at phosphorylate en renset target protein in vitro . (jove.com)
Previously, we found that eIF4A interacts with cyclin-dependent kinase A (CDKA), the plant ortholog of mammalian CDK1. (plantphysiol.org)
Olomoucine, a 2,6,9-trisubstituted purine, has been optimized for activity against CDK1/cyclin B by combinatorial and medicinal chemistry efforts to yield the purvalanol inhibitors. (lancs.ac.uk)

Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene . (wikipedia.org)
The protein encoded by this gene is a member of the Ser/Thr protein kinase family . (wikipedia.org)
This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product ( Rb ). (wikipedia.org)
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)
Initially, a mitogenic stimulus leads to the upregulation of cyclin D gene expression, which binds to CDK4. (news-medical.net)
p27(KIP1) is a member of the CIP1/KIP1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. (thefreedictionary.com)
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)
Cell division protein kinase 7 is an enzyme that in humans is encoded by the CDK7 gene . (wikidoc.org)
The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. (wikidoc.org)
M. Ubeda, D. M. Kemp, and J. F. Habener, "Glucose-induced expression of the cyclin-dependent protein kinase 5 activator p35 involved in Alzheimer's disease regulates insulin gene transcription in pancreatic β -cells," Endocrinology , vol. 145, no. 6, pp. 3023-3031, 2004. (hindawi.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 2.7.11.22 or EC 2.7.11.23) - Cell division protein kinase 7 is an enzyme that in humans is encoded by the CDK7 gene. (researchandmarkets.com)
CDKN2A (cyclin dependent kinase 2a / p16) Hybridization with Vysis CDKN2A/CEP 9 FISH Probe (Abbott Molecular, US) showing the CDKN2A gene on 9p21.3 (red signals) - Courtesy Adriana Zamecnikova. (atlasgeneticsoncology.org)
The cerebral cortex of mice with a targeted disruption in the gene for cyclin-dependent kinase 5 ( cdk5 ) is abnormal in its structure. (jneurosci.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)
The RV-cyclin increases CDK8 occupancy at the EGR1 gene locus before and after serum stimulation. (sigmaaldrich.com)
The gene codes for a protein, p15, which is an inhibitor of cyclin dependent kinases, and thus, acts as a negative regulator of cell proliferation. (cags.org.ae)
Mutations in the gene cause the protein to lose their capacity to block the Cyclin D/CDK activation, resulting in uncontrolled cell proliferations, and development of malignancies. (cags.org.ae)
This gene encodes a member of the p34Cdc2 protein kinase family. (antibodies-online.com)
The protein kinase encoded by this gene could be cleaved by caspases and was demonstrated to play roles in cell apoptosis. (antibodies-online.com)
2 Cyclin-dependent kinase inhibitors (CKIs) are naturally occurring gene products that inhibit the cyclin-CDK activity leading to G 1 arrest. (ahajournals.org)
A gene on chromosome 5q31 that encodes a CMGC-type serine/threonine protein kinase of unknown function, which is thought to have a cyclin-binding region. (thefreedictionary.com)
Activity of the kinase, determined by in vitro phosphorylation of recombinant truncated retinoblastoma tumor suppressor gene (Rb) protein (p60Rb), paralleled p40cdk6 protein amounts. (jimmunol.org)
Inducible deletion of the p35 gene in adult mice results in profound deficits in hippocampal-dependent spatial learning and synaptic physiology, however the impact of the loss of p35 function on hippocampal in vivo physiology and spatial coding remains unknown. (frontiersin.org)
A gene on chromosome 2q33.2 that encodes a cyclin-dependent serine/threonine-protein kinase involved in controlling the cell cycle. (thefreedictionary.com)
This raised the possibility that HIV-1 gene expression in renal epithelium may also be critically dependent on CDK that control RNA polymerase II activity on the HIV-1 promoter ( 10 ). (asnjournals.org)
Here, we show that the block to IE gene expression during S and G2 phase can be overcome by both genotoxic stress and chemical inhibitors of cellular DNA replication, pointing to the involvement of checkpoint-dependent signaling pathways in controlling IE gene repression. (prolekare.cz)
Thus, a timely block to CDK activity not only secures phase specificity of the cell cycle dependent HCMV IE gene expression program, but in addition plays a hitherto unrecognized role in preventing the establishment of a latent-like state. (prolekare.cz)
This gene encodes a member of a family of serine/threonine protein kinases that participate in cell cycle regulation. (creativebiomart.net)
To investigate this process, we reduced endoreduplication in transgenic maize endosperm by ectopically expressing a gene encoding a dominant negative mutant form of cyclin-dependent kinase A. This gene was regulated by the 27-kD γ-zein promoter, which restricted synthesis of the defective enzyme to the endoreduplication rather than the mitotic phase of endosperm development. (plantcell.org)

Involvement of p38 mitogen-activated protein kinase in basic fibroblast growth factor-induced interl. (biomedsearch.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)

[5] Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. (wikipedia.org)
Cyclin-CDK complexes phosphorylate substrates appropriate for the particular cell cycle phase. (wikipedia.org)
The ability of Cdk5 to phosphorylate substrates is dependent on activation by its neuronal-specific activators p35 and p39. (jneurosci.org)
Protein function: Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and. (biomol.com)
Protein function: Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. (biomol.com)
We isolated mouse mytl kinase which phosphorylate both T-14 and Y-15 in vitro. (nii.ac.jp)

An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) activator," Journal of Biological Chemistry , vol. 270, no. 45, pp. 26897-26903, 1995. (hindawi.com)
Identification of the 23 kDa subunit of tau protein kinase II as a putative activator of CDK5 in bovine brain," FEBS Letters , vol. 342, no. 2, pp. 203-208, 1994. (hindawi.com)
Cyclin-dependent kinase 5 (Cdk5) plays a pivotal role in brain development and neuronal migration. (jneurosci.org)
In the developing brain, proper neuronal migration depends on the activity of a serine/threonine kinase, Cyclin-dependent kinase 5 (Cdk5). (jneurosci.org)
Despite these studies, the specific role of the p39/Cdk5 kinase complex is not clear. (jneurosci.org)
p35 is an activating co-factor of Cyclin-dependent kinase 5 (Cdk5), a protein whose dysfunction has been implicated in a wide-range of neurological disorders including cognitive impairment and disease. (frontiersin.org)
Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase structurally homologous to the Cdk family members which modulate the cell cycle. (frontiersin.org)
Here we assessed the role played by the proline-directed serine/threonine kinase cyclin-dependent kinase 5 (Cdk5) in the nucleus accumbens (NAcc) on the expression of the conditioned locomotion normally observed when rats are returned to a context previously paired with amphetamine. (open.ac.uk)
Cyclin-dependent kinases from the Cdk5/Pho85 family are thought to play important roles in morphogenesis in organisms as diverse as yeast and humans. (biologists.org)
Here we used the corn smut fungus Ustilago maydis to address the role of Cdk5/Pho85 kinases in the morphogenesis and virulence of dimorphic phytopathogens. (biologists.org)
Cdk5 belongs to a family of cyclin-dependent kinases that seem to be involved in the control of cell differentiation and morphology rather than cell division ( Dhavan and Tsai, 2001 ). (biologists.org)

It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (wikipedia.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)
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 2.7.11.22 or EC 2.7.11.23) - Cyclin-dependent kinase 9 (CDK9) is a cyclin-dependent kinase associated with P-TEFb. (medindia.net)
This kinase was found to be a component of the multiprotein complex TAK/P-TEFb, which is an elongation factor for RNA polymerase II-directed transcription and functions by phosphorylating the C-terminal domain of the largest subunit of RNA polymerase II. (medindia.net)
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)
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 2.7.11.22 or EC 2.7.11.23) 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 2.7.11.22 or EC 2.7.11.23) targeted therapeutics development with respective active and dormant or discontinued projects. (medindia.net)
CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. (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 2.7.11.22 or EC 2.7.11.23) pipeline Target constitutes close to 11 molecules. (researchandmarkets.com)
The dimeric enzyme consists of a catalytic subunit, CDK and a regulatory subunit, cyclin. (psmarketresearch.com)
The encoded protein is the catalytic subunit of the cyclin-dependent protein kinase complex, which regulates progression through the cell cycle. (creativebiomart.net)
It also reviews key players involved in 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 2.7.11.22 or EC 2.7.11.23) targeted therapeutics development with respective active and dormant or discontinued projects. (marketresearch.com)

Addgene: AML1/RUNX1 phosphorylation by cyclin-dependent kinases regulates the degradation of AML1/RUNX1 by the anaphase-promoting complex. (addgene.org)
CYCLIN-DEPENDENT KINASE G2 regulates salinity stress response and salt mediated flowering in. (deepdyve.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)
Conversely, DNA damage after CHK1 inhibition is highly dependent on CDC25A. (rupress.org)
Conclusions -p27 Kip1 and p21 Cip1 are potent inhibitors of VSMC growth compared with p16 Ink4 because of their different molecular mechanisms of cyclin-dependent kinase inhibition in the G 1 phase of the cell cycle. (ahajournals.org)
The induction of cyclin D2 and the decrease in p27 were not inhibited by UP, whereas the induction of cyclin E, cyclin A, cyclin-dependent kinase-2, and cyclin-dependent kinase-4 was strongly inhibited, potentially explaining the inhibition of retinoblastoma protein phosphorylation. (jimmunol.org)
Checkpoint-dependent rescue of IE expression strictly requires p53 and in the absence of checkpoint activation is mimicked by proteasomal inhibition in a p53 dependent manner. (prolekare.cz)
Additional analysis demonstrated that flavopiridol treatment resulted in a dose-dependent inhibition of phosphorylation of the RNA polymerase II COOH-terminal domain, thus blocking transcription elongation. (aacrjournals.org)
In this article we report that stable short hairpin RNA-mediated cortactin knockdown in the 11q13-amplified cell line FaDu led to increased expression of the Cip/Kip cyclin-dependent kinase inhibitors (CDKIs) p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) and inhibition of S-phase entry. (garvan.org.au)

Vladimir Krystof, Sonja Baumli and Robert Furst, "Perspective of Cyclin-dependent kinase 9 (CDK9) as a Drug Target", Current Pharmaceutical Design (2012) 18: 2883. (eurekaselect.com)

Most of the known cyclin-CDK complexes regulate the progression through the cell cycle. (wikipedia.org)
Dominant-negative mutations were used to address the requirement for kinases of this family in progression through the human cell cycle. (sciencemag.org)
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. (curehunter.com)
Associated with cyclin-D, CDK4 phosphorylates and inactivates retinoblastoma (Rb) protein family members and mediates progression through the G1- to the S-phase of the cell cycle. (springer.com)
The Cdk:cyclin complexes of the G1/S transition regulate the progression of cells into the S phase by phosphorylating the retinoblastoma protein (Rb). (diva-portal.org)
Targeted degradation of the cyclin-dependent kinase inhibitor ICK4/KRP6 by RING-type E3 ligases is essential for mitotic cell cycle progression during Arabidopsis gametogenesis. (nextbio.com)
The founding member of this family, the Pho85 cyclin-dependent kinase, was isolated in Saccharomyces cerevisiae because of its involvement in the regulation of phosphate-scavenging enzymes, and it has been implicated in many other cellular processes, including stress adaptation, glycogen storage, cell cycle progression and morphogenesis (for a review, see Carroll and O'Shea, 2002 ). (biologists.org)

Several groups including our own have demonstrated that induction of cyclin-dependent kinase (CDK) inhibitor p27Kip1 protein is one of the key mechanisms of action of HER2-targeting antibodies. (nih.gov)
By inhibiting AKT and human kinase interacting stathmin (hKIS), trastuzumab blocks Thr157-, Thr198- and Ser10-induced p27Kip1 translocation from the nucleus to the cytosol, which increases the inhibitory effect of p27Kip1. (nih.gov)
This protein associates with and regulated by other subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A), and p27Kip1 (CDKN1B). (creativebiomart.net)

The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16 INK4a . (wikipedia.org)
Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. (wikipedia.org)
Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (wikipedia.org)
Upon external signals, CDK inhibitors can be used to block the CDK kinase activity, thereby preventing the cell cycle from being driven forward. (news-medical.net)
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)
Phosphorylation by CDK-activating kinase (CAK) at Thr 161 on the T-loop increases the complex activity. (wikipedia.org)
Full kinase activity requires an activating phosphorylation on a threonine adjacent to the CDK's active site. (wikipedia.org)
CAK activity is not regulated by known cell-cycle pathways and cyclin binding is the limiting step for CDK activation. (wikipedia.org)
this phosphorylation is thought to alter ATP orientation, preventing efficient kinase activity. (wikipedia.org)
At the onset of M phase, the activity of somatic Wee1 (Wee1A), the inhibitory kinase for cyclin-dependent kinase (CDK), is down-regulated primarily through proteasome-dependent degradation after ubiquitination by the E3 ubiquitin ligase SCF β-TrCP . (pnas.org)
Serine/threonine-protein kinase involved in the control of the eukaryotic cell cycle, whose activity is controlled by an associated cyclin. (uniprot.org)
It binds to cyclin-dependent kinase 8 (CDK8) and enhances its kinase activity. (sigmaaldrich.com)
It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18. (curehunter.com)
We conclude that the mitotic kinase WEE1 and CHK1 jointly maintain balanced cellular control of Cdk activity during normal DNA replication, which is crucial to prevent the generation of harmful DNA lesions during replication. (rupress.org)
The results show that the mitotic kinase WEE1 is crucial for genome integrity during S phase in a manner dependent on Cdk activity. (rupress.org)
This evidence suggests that the Cdkl kinase family might be involved in behavioral modification, activity-dependent synaptic plasticity, and learning. (frontiersin.org)
Shortly after its purification, P-TEFb was found to have protein kinase activity ( 50 ). (asm.org)
CKIs act as brakes for the cell cycle, restraining the activity of cyclin-CDK complexes to maintain cells in the quiescent G 0 /G 1 phase or to induce cell cycle exit in proliferating cells. (asm.org)
Flavopiridol and roscovitine, newly identified inhibitors of cyclin-dependent kinase-9, markedly decrease HIV-1 promoter activity in cell lines of various lineages. (asnjournals.org)
Recently, flavopiridol and roscovitine, small molecules that inactivate specific cell-cycle cyclin-dependent kinases (CDK), were found to inhibit CDK-9, markedly decreasing HIV-1 promoter activity in cell lines of various lineages ( 8 , 9 ). (asnjournals.org)
In vitro, wild-type recombinant eIF4A1 and its phospho-null variant both support translation in cell-free wheat germ extracts dependent upon eIF4A, but the phosphomimetic variant does not support translation and also was deficient in ATP hydrolysis and helicase activity. (plantphysiol.org)
The Cyclin-Dependent Protein Kinase Inhibitor Set controls the biological activity of Cyclin-Dependent Protein Kinase. (merckmillipore.com)
Dinaciclib is a novel cyclin-dependent kinase inhibitor with significant clinical activity in relapsed and refractory chronic lymphocytic leukemia. (osu.edu)
14-3-3 zeta protein did not affect the activity of weel kinase. (nii.ac.jp)
Overexpression of a wild-type cyclin-dependent kinase A increased enzyme activity but had no effect on endoreduplication. (plantcell.org)
By contrast, ectopic expression of the defective enzyme lowered kinase activity and reduced by half the mean C-value and total DNA content of endosperm nuclei. (plantcell.org)

OSI Pharmaceuticals, Inc., and Genentech, Inc.) is an orally available quinazolinamine that competes with ATP for binding with the intracellular catalytic domain of EGFR tyrosine kinase (EGFR-TK) to inhibit the phosphorylation of EGFR-TK. (pubmedcentralcanada.ca)

The key cell-cycle regulator Cdc2 belongs to a family of cyclin-dependent kinases in higher eukaryotes. (sciencemag.org)
Because it is a strong, tight inhibitor of several G1 cyclin/CDK complexes, this protein is a negative regulator of cell proliferation. (cags.org.ae)
Here, we have identified the cyclin-dependent kinase inhibitor p27 Kip1 as a critical regulator of the CD8 T-cell homeostasis at all phases of the T-cell response to an acute viral infection in mice. (asm.org)
Here, Arabidopsis thaliana CYCLIN-DEPENDENT KINASE G2 (CDKG2) was shown to act as a negative regulator of the salinity stress response, as well as being involved in the control of flowering time. (deepdyve.com)

Encodes a member of a plant specific family of cyclin dependent kinases. (nih.gov)

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)
These genes include cyclin E, which binds to CDK4, driving the cell cycle into the S phase. (news-medical.net)
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)
Cyclin-CDK complexes of earlier cell-cycle phase help activate cyclin-CDK complexes in later phase. (wikipedia.org)
cyclin L CDK levels remain relatively constant throughout the cell cycle and most regulation is post-translational. (wikipedia.org)
Modulation of cyclin accumulation, and thereby Cdk activation, was proposed to be the overarching principle governing the passage through cell cycle phases. (springer.com)
Wee1 family protein kinases that inhibit Cdc2 during the G 2 phase of the cell cycle must be down-regulated at the onset of mitosis. (pnas.org)
Western blotting was used to measure cyclin-dependent kinase (CDK) inhibitors p21 and p27 that arrest cell cycle. (thefreedictionary.com)
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)
Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. (uniprot.org)
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)
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)
Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. (curehunter.com)
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. (harvard.edu)
Cyclin D3 is strongly induced in the DN4 and immature single-positive (ISP) compartments following pre-T-cell receptor (TCR) assembly. (aacrjournals.org)
p34Cdc2 kinase family members are known to be essential for eukaryotic cell cycle control. (antibodies-online.com)
The CKIs p27 Kip1 and p21 Cip1 inactivate the cyclin-CDK complexes in the G 1 phase leading to cell cycle arrest, and thus function in growth regulation and wound repair. (ahajournals.org)
CDK with cyclin combines to form a cyclin-CDK complex for the regulation of cell cycle. (psmarketresearch.com)
Combined, the data demonstrate that the intracellular localization of PTHrP is phosphorylation- and cell cycle-dependent, and such control further supports a potential intracellular role (10,34,35) for PTHrP. (garvan.org.au)
Cell and organ growth are profoundly dependent on protein production, a process that provides the building blocks for new cellular components. (plantphysiol.org)
These Cdk/cyclin complexes reportedly regulate each step of the cell cycle. (merckmillipore.com)
When both weel kinase and 14-3-3 zeta were transfected into COS-1 cells, they formed a complex in a cell. (nii.ac.jp)
The weel kinase phosphorylates only Y-15 residue of cdc2 kinase and T-14 phosphorylation is observed in a intact cell. (nii.ac.jp)
The latest report Cyclin Dependent Kinase 4 - Pipeline Review, H2 2017, outlays comprehensive information on the Cyclin Dependent Kinase 4 (Cell Division Protein Kinase 4 or PSK J3 or CDK4 or EC 2.7.11.22) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (reportsnreports.com)
Furthermore, this report also reviews key players involved in Cyclin Dependent Kinase 4 (Cell Division Protein Kinase 4 or PSK J3 or CDK4 or EC 2.7.11.22) targeted therapeutics development with respective active and dormant or discontinued projects. (reportsnreports.com)
These therapeutic effects might result from p27 Kip1 -dependent suppression of both cell proliferation and migration. (ahajournals.org)
Moreover, a constitutively active mutant of the retinoblastoma protein (pRb) insensitive to CDK-dependent hyperphosphorylation inhibited both cell proliferation and migration. (ahajournals.org)
CDK-dependent pRb hyperphosphorylation releases E2F transcription factors, thus contributing to the expression of several growth and cell cycle-regulatory genes with functional E2F-binding sites in their promoters. (ahajournals.org)
The cyclin-dependent kinase inhibitor 1A (CDKN1A), also known as p21 (WAF1/CIP1) modulates cell cycle, apoptosis, senescence and differentiation via specific protein-protein interactions with the cyclins, cyclin-dependent kinase (Cdk), and many others. (semanticscholar.org)

Cyclin-dependent kinase-like 2 (Cdkl2) is a cdc2-related serine/threonine protein kinase that is postnatally expressed in various brain regions, including the cerebral cortex, entorhinal cortex, hippocampus, amygdala, and dorsal thalamus. (frontiersin.org)
The weel kinase phosphorylated by cdc2 kinase also bound to 14-3-3 zeta ptotein. (nii.ac.jp)
Further, cyclin B/cdc2 kinase, weel kinase and 14-3-3 zeta ptotein form a complex. (nii.ac.jp)
The other kinase which phosphorylates T-14 of cdc2 kinase must exist. (nii.ac.jp)
Publications] Nagai,Y.: 'Ubiquitin-activating enzyme,E1, is phosphorylated in mammalidn cells by the protein kinase cdc2. (nii.ac.jp)

One of the kinases that place the tyrosine phosphate is Wee1, a kinase conserved in all eukaryotes. (wikipedia.org)
Inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinases,such as erlotinib and gefitinib, have not been very effective in the treatment of breast cancer although many breast cancer cells express EGFR. (pubmedcentralcanada.ca)
Expression of phosphorylated (p-)tyrosine, p-Akt, phosphorylated extracellular signal-regulated kinase (p-ERK) 1/ERK2 (p42/p44), and p27 after treatment of erlotinib was not associated with erlotinib sensitivity. (pubmedcentralcanada.ca)

It has been demonstrated that drug-resistant cancer cells can arise during therapeutic application of small molecule protein kinase inhibitors. (eurekaselect.com)

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)
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)
We found that leaf cells facing the cut undergo CDK activation along with induction of a D-type cyclin, tip growth, and transcriptional activation of protonema-specific genes. (deepdyve.com)

Regulation of cyclin-dependent kinases in Arabidopsis thaliana. (nih.gov)
The four major mechanisms of CDK regulation are cyclin binding, CAK phosphorylation, regulatory inhibitory phosphorylation, and binding of CDK inhibitory subunits (CKIs). (wikipedia.org)
The heterogeneity of kinases involved in phospho-regulation provides a fundamental basis for the sequential biochemical reactions that underlie the mechanisms of synaptic plasticity. (frontiersin.org)
The function of 14-3-3 zeta protein remained to be elucidated in relationto the regulation of G2 to M phase transition through weel kinase. (nii.ac.jp)

Another one, CDK7, is involved indirectly as the CDK-activating kinase. (wikipedia.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)

These effects were associated with increased binding of p21(WAF1/Cip1) and p27(Kip1) to cyclin D1- and E1-containing complexes and decreased retinoblastoma protein phosphorylation. (garvan.org.au)
UV radiation is a transcriptional inducer of p21(Cip1/Waf1) cyclin-kinase inhibitor in a p53-independent manner. (semanticscholar.org)

Benson C, Kaye S, Workman P, Garrett M, Walton M, de Bono J. Clinical anticancer drug development: targeting the cyclin-dependent kinases. (springer.com)
Vladimir Krystof and Stjepan Uldrijan, " Cyclin-Dependent Kinase Inhibitors as Anticancer Drugs", Current Drug Targets (2010) 11: 291. (eurekaselect.com)
OTAVA provides compound libraries for screening and it offers custom synthesis and molecular modeling services, targeted compound libraries and protein kinase inhibitors, prescreened anticancer compounds, peptide and chromogenic substrates. (hum-molgen.org)

Finally, cyclin B binds to CDK-1 to drive the cycle forward into M phase, stimulating mitosis. (news-medical.net)
By definition, a CDK binds a regulatory protein called a cyclin. (wikipedia.org)
There is considerable specificity in which cyclin binds with CDK. (wikipedia.org)
Publications] Honda,R.: '14-3-3protein binds to the carboxy half of mouse wee1 kinase' Biochem.Biophys.Res.Commun.230. (nii.ac.jp)
Publications] Honda, R., Ohba, Y., and Yasuda, H.: '14-3-3 zeta ptotein binds to the carboxyl half of mouse weel kinase. (nii.ac.jp)

Characterization of the new immunosuppressive drug undecylprodigiosin in human lymphocytes: retinoblastoma protein, cyclin-dependent kinase-2, and cyclin-dependent kinase-4 as molecular targets. (jimmunol.org)
Intracellular targets of cyclin-dependent kinase inhibitors: identification by affinity chromatography using immobilised inhibitors. (lancs.ac.uk)
Conclusions: That a simple batchwise affinity chromatography approach using two purine derivatives facilitated isolation of a small set of highly purified kinases suggests that this could be a general method for identifying intracellular targets relevant to a particular class of ligands. (lancs.ac.uk)

Furthermore, cyclin binding determines the specificity of the cyclin-CDK complex for particular substrates. (wikipedia.org)
At least some cyclins contain a hydrophobic patch which may directly interact with substrates, conferring target specificity. (wikipedia.org)

Kinases regulate many essential cellular processes. (thefreedictionary.com)
Bivariate distribution of cyclin B1 or p21 expression versus cellular DNA content was assessed by flow cytometry. (jrheum.org)
Wang, Mei 2015-05-07 00:00:00 Cyclin-dependent protein kinases are involved in many crucial cellular processes and aspects of plant growth and development, but their precise roles in abiotic stress responses are largely unknown. (deepdyve.com)

Using a specific inhibitor of CK2, we showed that the phosphorylation-dependent degradation of Wee1A is important for the proper onset of mitosis. (pnas.org)
Mitogenic and antimitogenic stimuli affect the rates of synthesis and degradation of CKIs as well as their redistribution among different CDK/cyclin pairs. (ahajournals.org)

Ruiling Zhang and team from Xinxiang Medical University explored the correlation between cyclin-dependent kinase 5 expression in the hippocampus and neurological impairments following prenatal ethanol exposure, and found that prenatal ethanol exposure could affect cyclin-dependent kinase 5 and its activator p35 in the hippocampus of offspring rats. (thefreedictionary.com)
Both of RV-cyclin's functional domains, i.e., the cyclin box and the activation domain, are necessary for the overall enhancement of IEG expression. (sigmaaldrich.com)
Extracellular-Regulated Protein Kinase 5-Mediated Control of p21 Expression Promotes Macrophage Proliferation Associated with Tumor Growth and Metastasis. (harvard.edu)
Background -The cyclin-dependent kinase inhibitors (CKIs) have different patterns of expression in vascular diseases. (ahajournals.org)
Expression of cyclin B1 and cyclin dependent kinase inhibitor p21 in lymphocytes in patients with systemic lupus erythematosus. (jrheum.org)
We measured the expression of cyclin B1 and CDK inhibitor p21 in peripheral blood lymphocytes (PBL) from patients with SLE and controls. (jrheum.org)
Expression of cyclin B1 was similar in all groups. (jrheum.org)

The report provides a competitor evaluation in the field of synthetic molecules targeting polo-like kinase 1 (Plk-1), cyclin-dependent kinase (CDK) or aurora kinase for treatment of cancer as of September 2011. (thefreedictionary.com)

OBJECTIVE: The roles of cyclins and cyclin dependent kinase (CDK) inhibitors of lymphocytes in the pathogenesis of systemic lupus erythematosus (SLE) are unclear. (jrheum.org)

Vi beskriver også rensning protokoller, der giver meget rene og homogen protein præparater egnet til kinase assay, og et bindende assay funktionelle verifikation af de identificerede fosforylering websteder, som sonder samspillet mellem en klassisk nukleare lokalisering signal (cNLS) og dens nukleare transport receptor karyopherin α. (jove.com)

Targeting cyclins and cyclin-dependent kinases in cancer: lessons from mice, hopes for therapeutic applications in human. (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)
These findings suggest that Cdkl2 is involved in cognitive function and provide in vivo evidence for the function of Cdkl family kinases expressed in terminally differentiated neurons in mice. (frontiersin.org)

Publications] Honda, R.: 'Mouse p87 wee1 kinase is regulated by M-phase specific phosphorylation' Chromosome Res.3. (nii.ac.jp)

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)
Without cyclin, a flexible loop called the activation loop or T-loop blocks the cleft, and the position of several key amino acid residues is not optimal for ATP-binding. (wikipedia.org)
Oxidative stress induces nucleo-cytoplasmic translocation of pancreatic transcription factor PDX-1 through activation of c-Jun NH 2 -terminal kinase," Diabetes , vol. 52, no. 12, pp. 2896-2904, 2003. (hindawi.com)
Previous work showed that the retroviral cyclin (RV-cyclin), encoded by WDSV, has separable cyclin box and transcription activation domains. (sigmaaldrich.com)
This action blocks downstream signal transduction and inhibits the tumorigenic effects associated with ligand-dependent and ligand-independent EGFR activation ( 1 , 2 ). (pubmedcentralcanada.ca)
Activation of the cyclin-D-CDK4 complex appears to require other factors such as recruitment of the substrate via a substrate recruitment motif, and/or formation of the CDKN1B ternary complex. (reportsnreports.com)

This destruction of M cyclins leads to the final events of mitosis (e.g., spindle disassembly, mitotic exit). (wikipedia.org)

Lactoferrin inhibits G1 cyclin-dependent kinases during growth arrest of human breast carcinoma cells. (biomedsearch.com)

Anatomy15

Organisms8

Diseases2

Chemicals and Drugs164

Analytical, Diagnostic and Therapeutic Techniques and Equipment14

Phenomena and Processes48

Disciplines and Occupations1

Information Science3

Activation of telomerase and its association with G1-phase of the cell cycle during UVB-induced skin tumorigenesis in SKH-1 hairless mouse. (1/4016)

Comparative molecular genetic profiles of anaplastic astrocytomas/glioblastomas multiforme and their subsequent recurrences. (2/4016)

The role of RBF in the introduction of G1 regulation during Drosophila embryogenesis. (3/4016)

Coupling of the cell cycle and myogenesis through the cyclin D1-dependent interaction of MyoD with cdk4. (4/4016)

Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. (5/4016)

Induced expression of p16(INK4a) inhibits both CDK4- and CDK2-associated kinase activity by reassortment of cyclin-CDK-inhibitor complexes. (6/4016)

Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (7/4016)

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. (8/4016)

No data available that match "cyclin dependent kinases"

Cyclin-Dependent Kinases

Cyclin-Dependent Kinase 2

Cyclin D1

Cyclin A

Cyclin E

Cyclins

Cyclin-Dependent Kinase 4

Cyclin-Dependent Kinase Inhibitor p27

CDC2-CDC28 Kinases

Cell Cycle

Cyclin-Dependent Kinase Inhibitor p21

Cyclin-Dependent Kinase 5

Cell Cycle Proteins

Cyclin B

Cyclin C

Protein-Serine-Threonine Kinases

CDC2 Protein Kinase

Cyclin D

G1 Phase

Cyclin-Dependent Kinase Inhibitor p16

Cyclin-Dependent Kinase Inhibitor Proteins

Cyclin D3

Cyclin B1

Retinoblastoma Protein

Phosphorylation

Cyclin-Dependent Kinase 6

Cyclin-Dependent Kinase Inhibitor p57

Tumor Suppressor Proteins

S Phase

Protein Kinase Inhibitors

Cyclin D2

Cyclin A1

Microtubule-Associated Proteins

Protein Kinases

Cell Proliferation

Purines

Cell Division

Apoptosis

Proto-Oncogene Proteins

E2F1 Transcription Factor

Cyclin A2

Phosphatidylinositol 3-Kinases

Cyclin G

Cell Line, Tumor

Tumor Cells, Cultured

Tumor Suppressor Protein p53

Mitosis

Cyclin G1

MAP Kinase Signaling System

Transcription Factor DP1

Signal Transduction

Cells, Cultured

Blotting, Western

Enzyme Inhibitors

G2 Phase

E2F Transcription Factors

Transfection

Calcium-Calmodulin-Dependent Protein Kinases

Mutation

Proliferating Cell Nuclear Antigen

Molecular Sequence Data

Cell Line

DNA-Binding Proteins

Carrier Proteins

Nuclear Proteins

Base Sequence

RNA, Messenger

Protein Kinase C

Transcription Factors

src-Family Kinases

Immunohistochemistry

Reverse Transcriptase Polymerase Chain Reaction

DNA Damage

Antineoplastic Agents

Amino Acid Sequence

p38 Mitogen-Activated Protein Kinases

Cyclic AMP-Dependent Protein Kinases

Cyclin B2

Mitogen-Activated Protein Kinase 1

Protein Binding