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
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
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
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
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.

A premature-termination mutation in the Mus musculus cyclin-dependent kinase 3 gene. (1/18)

Our understanding of the mammalian cell cycle is due in large part to the analysis of cyclin-dependent kinase (CDK) 2 and CDK4/6. These kinases are regulated by E and D type cyclins, respectively, and coordinate the G(1)/S-phase transition. In contrast, little is known about CDK3, a homolog of CDK2 and cell division cycle kinase 2 (CDC2). Previous studies using ectopic expression of human CDK3 suggest a role for this kinase in the G(1)/S-phase transition, but analysis of the endogenous kinase has been stymied by the low levels of protein present in cells and by the absence of an identifiable cyclin partner. Herein we report the presence of a single point mutation in the CDK3 gene from several Mus musculus strains commonly used in the laboratory. This mutation results in the replacement of a conserved tryptophan (Trp-187) within kinase consensus domain IX with a stop codon. The protein predicted to be encoded by this allele is truncated near the T loop, which is involved in activation by CDK-activating kinase. This mutation also deletes motif XI known to be required for kinase function and is, therefore, expected to generate a null allele. In stark contrast, CDK3 from two wild-mice species (Mus spretus and Mus mus castaneus) lack this mutation. These data indicate that CDK3 is not required for M. musculus development and suggest that any functional role played by CDK3 in the G(1)/S-phase transition is likely to be redundant with another CDK.  (+info)

ik3-1/Cables is a substrate for cyclin-dependent kinase 3 (cdk 3). (2/18)

p70ik3-1 (a 70-kDa protein) contains a cyclin box, and binds to p35cdk3 in vivo and in vitro [Matsuoka, M., Matsuura, Y., Semba, K. & Nishimoto, I. (2000) Biochem. Biophys. Res. Commun. 273, 442-447]. In spite of its structural similarity to cyclins, p70ik3-1 does not activate cyclin-dependent kinase 3 (cdk3)-mediated phosphorylation of pRb, histone H1, or the C-terminal domain of RNA polymerase II. Here, we report that Ser274 of p70ik3-1 is phosphorylated by cdk2 or cdk3 bound to cyclin A and to cyclin E in vitro. We also found that in COS7 cells in which cyclin E and cdk3 were ectopically overexpressed, the phosphorylation level of Ser274 in coexpressed p70ik3-1 is upregulated. We therefore conclude that p70ik3-1 is a substrate for cdk3-mediated phosphorylation.  (+info)

ik3-2, a relative to ik3-1/cables, is associated with cdk3, cdk5, and c-abl. (3/18)

A cDNA coding for ik3-2 (designated as ik3-2 from an interactor-2 with cdk3) was cloned by cross-hybridization with ik3-1 and RT-PCR. Analysis of amino acid sequence indicated that ik3-2 has the C-terminal cyclin-box-like region highly homologous to that of ik3-1 (identity in amino acids: 78%). On the other hand, the remainder of ik3-2 gene is not so similar to that of ik3-1. There are several regions other than the C-terminal cyclin-box-like region that are conserved between ik3-1 and ik3-2. In vivo binding assay indicated that like ik3-1, ik3-2 binds to cdk3, cdk5, and c-abl, although ik3-2 binds to cdk3 weakly as compared with ik3-1. The C-terminal cyclin-box-like region of ik3-2 (123 amino acids) is able to be associated with cdk5. Accordingly, ik3-2 is very similar to ik3-1 concerning its molecular interaction with other molecules, suggesting that ik3-2 function in the same biological field as ik3-1. Northern blot analysis indicated that ik3-2 is expressed ubiquitously all over tissues.  (+info)

Cyclin C/cdk3 promotes Rb-dependent G0 exit. (4/18)

G0 is a physiological state occupied by resting or terminally differentiated cells that have exited the cell cycle. In contrast to the well-characterized cyclin/cdk-mediated inactivation of pRb that controls the G1/S transition, little is known about regulation of the G0/G1 transition. However, pRb is likely to participate in this process because its acute somatic inactivation is sufficient for G0-arrested cells to re-enter the cell cycle. One physiological regulator of this event may be cyclin C because its highest mRNA levels occur during G0 exit. Here we show that a non-cdk8-associated cellular pool of cyclin C combines with cdk3 to stimulate pRb phosphorylation at S807/811 during the G0/G1 transition, and that this phosphorylation is required for cells to exit G0 efficiently. Thus, G1 entry is regulated in an analogous fashion to S phase entry, but involves a distinct cyclin/cdk combination.  (+info)

Cyclin C makes an entry into the cell cycle. (5/18)

From yeast to humans, cell cycle progression is orchestrated by the oscillation of kinase activities associated with cyclins. In an article published recently in Cell, Ren and Rollins investigate mechanisms controlling the G0/G1 transition in quiescent cells and identify new cyclin C/Cdk3 complexes as key regulators of cell cycle reentry in human cells.  (+info)

Absolute quantification of multisite phosphorylation by selective reaction monitoring mass spectrometry: determination of inhibitory phosphorylation status of cyclin-dependent kinases. (6/18)

Multisite phosphorylation is an important mechanism for achieving intricate regulation of protein function. Here we extended the absolute quantification of abundance (AQUA) methodology and validated its applicability to quantitatively study multisite phosphorylation. As a test case, we chose the conserved inhibitory site of the cyclin-dependent kinases (CDKs), Cdk1, Cdk2, and Cdk3, which are important regulators of cell cycle transitions and apoptosis. Inhibitory phosphorylation at Thr(14) and Tyr(15) of the CDKs is modulated by complex regulatory mechanisms involving multiple kinases and phosphatases. Yet the resulting quantitative dynamics among the four possible phosphorylated and non-phosphorylated versions of CDKs (T14p-Y15p, T14p-Y15, T14-Y15p, and T14-Y15) has not been investigated to date. Hence we used the heavy isotope-labeled tryptic peptides spanning the inhibitory site as internal standards and quantified all four versions by LC-selected reaction monitoring. Quantification of the phosphorylation status of the inhibitory site in the cell extracts provided novel quantitative insights. 1) The transition to mitotic phase was dominated by the conversion of "T14p-Y15p" to the "T14-Y15" form, whereas the two monophosphorylated forms were considerably lower in abundance. 2) The amount of all four forms decreased during the progression of apoptosis but with differing kinetics. Analysis of immunoprecipitated Cdk1 and Cdk2 revealed that the inhibitory site phosphorylation state of both kinases at different stages of the cell cycle followed the same trend. Quantitative immunoblotting using antibodies to Cdk1 and Cdk2 and to the T14-Y15p form suggested that quantification by AQUA was reliable and accurate. These results highlight the utility of internal standard peptides to achieve accurate quantification of multisite phosphorylation status.  (+info)

Cyclin-dependent kinase 3-mediated activating transcription factor 1 phosphorylation enhances cell transformation. (7/18)


Cyclin C and cyclin dependent kinases 1, 2 and 3 in thrombin-induced neuronal cell cycle progression and apoptosis. (8/18)


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TY - JOUR. T1 - Synergistic repression of thyroid hyperplasia by cyclin C and Pten. AU - Jezek, Jan. AU - Wang, Kun. AU - Yan, Ruilan. AU - Di Cristofano, Antonio. AU - Cooper, Katrina F.. AU - Strich, Randy. PY - 2019/8/15. Y1 - 2019/8/15. N2 - The cyclin C-Cdk8 kinase has been identified as both a tumor suppressor and an oncogene depending on the cell type. The genomic locus encoding cyclin C (Ccnc) is often deleted in aggressive anaplastic thyroid tumors. To test for a potential tumor suppressor role for cyclin C, Ccnc alone, or Ccnc in combination with a previously described thyroid tumor suppressor Pten, was deleted late in thyroid development. Although mice harboring individual Pten or Ccnc deletions exhibited modest thyroid hyperplasia, the double mutant demonstrated dramatic thyroid expansion resulting in animal death by 22 weeks. Further analysis revealed that Ccncthyr-/- tissues exhibited a reduction in signal transducer and activator of transcription 3 (Stat3) phosphorylation at ...
Survival analysis is long-established within actuarial science but infrequently used in general data science projects. We explain more with worked examples.
Xu W, Ji JY (2011). "Dysregulation of CDK8 and Cyclin C in tumorigenesis". J Genet Genomics. 38 (10): 439-52. doi:10.1016/j.jgg ... Mediator can be divided onto 4 main parts: The head, middle, tail, and the transiently associated CDK8 kinase module. Mediator ... Grueter CE (2013). "Mediator complex dependent regulation of cardiac development and disease". Genomics Proteomics ... Clark AD, Oldenbroek M, Boyer TG (2015). "Mediator kinase module and human tumorigenesis". Crit Rev Biochem Mol Biol. 50 (5): ...
He has received several awards for his research in cyclin-dependent kinases and their role in cell cycle and cancer growth. He ... is married to Martine Roussel, a biologist, and has 3 children. 1995 Elected member of the National Academy of Sciences 1995 ...
... a cyclin-dependent kinase inhibitor, is dependent on p53 signaling. PLoS One, 8(3):e59588 doi:10:1371/journal.pone.0059588, ... 3:1-4, 2013. "Meenhard Herlyn, D.V.M., D.Sc". The Wistar Institute. Retrieved 12 February 2014. CS1 maint: discouraged ...
De Azevedo WF, Leclerc S, Meijer L, Havlicek L, Strnad M, Kim SH (1997). "Inhibition of cyclin-dependent kinases by purine ... Doree M, Galas S (1994). "The cyclin-dependent protein kinases and the control of cell division". FASEB J. 8 (14): 1114-1121. ... Seliciclib (roscovitine or CYC202) is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase ( ... Schang LM, Rosenberg A, Schaffer PA (2000). "Roscovitine, a specific inhibitor of cellular cyclin-dependent kinases, inhibits ...
Regulation of telomere elongation by the cyclin-dependent kinase CDK1. „Mol Cell". 24 (3), s. 423-32, Nov 2006. DOI: 10.1016/j. ... Kinase-independent functions of TEL1 in telomere maintenance.. „Mol Cell Biol". 29 (18), s. 5193-202, Sep 2009. DOI: 10.1128/ ... Od 1988 do 1990 odbyła staż podoktorancki (postdoctoral fellowship) w Cold Spring Harbor Laboratory, Long Island[3]. Prowadziła ... Tę stronę ostatnio edytowano 11:22, 3 lut 2017.. *Tekst udostępniany na licencji Creative Commons: uznanie autorstwa, na tych ...
... and cyclin-dependent protein kinase 5 (Cdk5) are highly expressed in Alzheimer's disease and are some of the protein kinases ... revealing the presence of both Rho kinase-dependent and Rho kinase-independent pathways for the growth cone collapse. In RhoA ... Ca2+/calmodulin-dependent protein kinase II (CaMK II) is also activated by calcium influx through NMDA receptors, and is ... Rho-kinase subsequently phosphorylates CRMP-2 on Threonine-555 (Thr555). In DRG neurons, CRMP-2 is phosphorylated by Rho kinase ...
CDK4, CMM3, PSK-J3, cyclin-dependent kinase 4, cyclin dependent kinase 4. ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. Sci. U.S. ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ...
CDKN2C, INK4C, p18, p18-INK4C, cyclin-dependent kinase inhibitor 2C, cyclin dependent kinase inhibitor 2C. ... CDKN2C‏ (Cyclin dependent kinase inhibitor 2C) هوَ بروتين يُشَفر بواسطة جين CDKN2C في الإنسان.[1][2][3] ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". مؤرشف من الأصل في 05 ديسمبر 2010.. الوسيط , ... negative regulation of cyclin-dependent protein serine/threonine kinase activity. • G1/S transition of mitotic cell cycle. • ...
"Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proceedings of the National ... protein serine/threonine kinase activity. • cyclin-dependent protein serine/threonine kinase activity. ... The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate ... "Entrez Gene: CDK8 cyclin-dependent kinase 8".. *^ Nemet J, Jelicic B, Rubelj I, Sopta M (Feb 2014). "The two faces of Cdk8, a ...
The cyclin-dependent kinase inhibitor p21 is induced by both p53-dependent and p53-independent mechanisms and can arrest the ... ISBN 978-1-58829-500-2.[page needed] Gartel AL, Tyner AL (June 2002). "The role of the cyclin-dependent kinase inhibitor p21 in ... cell cycle at the G1/S and G2/M checkpoints by deactivating cyclin/cyclin-dependent kinase complexes. The SOS response is the ... In one of the earliest steps, the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), phosphorylates SIRT6 on ...
cyclin binding. • cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine ... CDKN1A, CAP20, CDKN1, CIP1, MDA-6, P21, SDI1, WAF1, p21CIP1, cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase ... also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) ... 1994). "p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest ...
To this end, ViroStatics has focused on selectively targeting the Cyclin Dependent Kinases (CDKs) involved in these ... 3 corporation pursuing innovative antiviral therapies and vaccine research. Led by CEO Franco Lori, MD, PhD, ViroStatics has ...
... , NCK5AI, P39, p39nck5ai, cyclin-dependent kinase 5, regulatory subunit 2 (p39), cyclin dependent kinase 5 regulatory ... cyclin-dependent protein kinase 5 activator activity. • lipid binding. Cellular component. • cytoplasm. • cyclin-dependent ... 2002). "The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent ... positive regulation of protein kinase activity. • regulation of cyclin-dependent protein serine/threonine kinase activity. • ...
... phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase" ... A dose-dependent response was not observed, raising questions about the robustness of the findings.[21] ... of cellular CDK9 and cyclin T1, and hence increases the production of full-length viral RNA.[8] ... III-3-III-18 *^ Kim JB, Sharp PA (April 2001). "Positive transcription elongation factor B ...
de Nooij JC; Graber KH; Hariharan IK (2001). "Expression of cyclin-dependent kinase inhibitor Dacapo is regulated by cyclin E ... Entry into endocycles involves modulation of mitotic and S-phase cyclin-dependent kinase (CDK) activity. Inhibition of M-phase ... "A Dominant Negative Mutant of Cyclin-Dependent Kinase A Reduces Endoreduplication but Not Cell Size or Gene Expression in Maize ... "The cell cycle in polyploid megakaryocytes is associated with reduced activity of cyclin B1-dependent cdc2 kinase". Journal of ...
... play a crucial role in cell cycle regulation by dephosphorylating cyclin-dependent kinases, most importantly CDK2. PTEN and ... Mitogen-activated protein Kinase Phosphatases (MKPs) MKPs form a rather large family, with some 11 well-characterized members. ... They are responsible for the dephosphorylation of active mitogen-activated protein kinases (MAPKs). In accordance with this ... Phosphatases of Regenerating Liver (PRLs): Three PRL genes were described in mammals (PRL-1, PRL-2 and PRL-3). They share a ...
Cyclin D, Cyclin E transcriptional regulators: Myc, E2f1, p130 cyclin-dependent kinase inhibitors (CKIs): p27Kip1, p21, Wee1 ... βTRCP recognizes these substrates after they are phosphorylated by Polo-like kinase 1 or Cyclin B-CDK1. Fbw7, which is the ... Schwob, E (1994-10-21). "The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae". Cell. 79 ... SCF-fbxo4 plays a role in cell cycle control by targeting cyclin D1 for degradation. Cyclin F is an FBP that is associated with ...
"Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational ... 9 (3): 145-53. doi:10.1038/nchembio.1158. PMID 23416400.. *^ Vona B, Maroofian R, Bellacchio E, Najafi M, Thompson K, Alahmad A ... 3 (9): 954-60. PMID 9292495.. *^ Kaiser F, Bittrich S, Salentin S, Leberecht C, Haupt VJ, Krautwurst S, Schroeder M, Labudde D ... It aminoacylates at the 3'-OH of a terminal adenosine on tRNA, and is usually dimeric or tetrameric (two or four subunits, ...
... cyclin-dependent kinase 5 MeSH D12.644.360.250.067.900 - cyclin-dependent kinase 9 MeSH D12.644.360.250.323 - cyclin-dependent ... map kinase kinase kinase 1 MeSH D12.644.360.400.200 - map kinase kinase kinase 2 MeSH D12.644.360.400.300 - map kinase kinase ... kinase 2 MeSH D12.644.360.250.451 - cyclin-dependent kinase 4 MeSH D12.644.360.250.515 - cyclin-dependent kinase 6 MeSH D12.644 ... map kinase kinase 1 MeSH D12.644.360.440.200 - map kinase kinase 2 MeSH D12.644.360.440.300 - map kinase kinase 3 MeSH D12.644. ...
... protects neurons by inhibiting cyclin-dependent kinase". European Journal of Neuroscience. 28 (10): 2003-2016. doi:10.1111/j. ... C16 (PKRi, GW 506033X) is a drug which acts as a selective inhibitor of the enzyme double-stranded RNA-dependent protein kinase ... S-17092 Jammi, NV; Whitby, LR; Beal, PA (Aug 2003). "Small molecule inhibitors of the RNA-dependent protein kinase". ... Shimazawa, M; Hara, H (Dec 2006). "Inhibitor of double stranded RNA-dependent protein kinase protects against cell damage ...
... pyrimidine Is a Potent Inhibitor of Cyclin-Dependent Protein Kinases 1, 2, and 9, Which Demonstrates Antitumor Effects in Human ... "The Development of a Selective Cyclin-Dependent Kinase Inhibitor That Shows Antitumor Activity". Cancer Research. 69 (15): 6208 ... unmet medical need with the invention of highly selective and bioavailable inhibitors of the Cyclin Dependent Kinases including ... "Total Synthesis of TAK-Kinase Inhibitor LL-Z1640-2 via Consecutive Macrocyclization and Transannular Aromatization". Organic ...
The cyclin-dependent kinase inhibitor SCH 727965 (dinacliclib) induces the apoptosis of osteosarcoma cells. „Mol Cancer Ther". ... Glycogen synthase kinase-3β, NF-κB signaling, and tumorigenesis of human osteosarcoma. „J Natl Cancer Inst". 104 (10), s. 749- ... Clinical and biological significance of PIM1 kinase in osteosarcoma. „J Orthop Res", Dec 2015. DOI: 10.1002/jor.23134. PMID: ... Transgenic expression of E2F3a causes DNA damage leading to ATM-dependent apoptosis. „Oncogene". 27 (36), s. 4954-61, Aug 2008 ...
Nguyen, Van Q.; Co, Carl; Li, Joachim J. (2001). "Cyclin-dependent kinases prevent DNA re-replication through multiple ... the pre-replication complex only occurs during late M phase and early G1 phase of the cell cycle when cyclin-dependent kinase ( ... The singular archaeal ORC protein recognizes the AT-rich tracts and binds DNA in an ATP-dependent fashion. Eukaryotes typically ... "DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent on Cdt2 and Ddb1". EMBO Reports. 7 (11): 1134- ...
de 2002). «Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4». Mol. Cell ... cyclins and cyclin dependent kinases». Oncogene (ENGLAND) 15 (2): 143-57. ISSN 0950-9232. PMID 9244350. doi:10.1038/sj.onc. ... a b «Entrez Gene: CDK2 cyclin-dependent kinase 2». *↑ Berthet C, Aleem E, Coppola V, Tessarollo L, Kaldis P (octubre de 2003). ... de 1994). «KAP: a dual specificity phosphatase that interacts with cyclin-dependent kinases». Proc. Natl. Acad. Sci. U.S.A. ( ...
... cyclins and cyclin dependent kinases». Oncogene. 15 (2): 143-57. PMID 9244350. doi:10.1038/sj.onc.1201252. !CS1 manut: Nomes ... cyclins and cyclin dependent kinases». Oncogene. 15 (2): 143-57. PMID 9244350. doi:10.1038/sj.onc.1201252. A referência emprega ... BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site». Mol. Cell. Biol. 19 (7): ... BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3». ...
A prominent kinase is cyclin-dependent kinase (or CDK), which comprises a sub-family of protein kinases. As their name implies ... "Biochemical characterization of the human cyclin-dependent protein kinase activating kinase. Identification of p35 as a novel ... CDKs are heavily dependent on specific cyclin molecules for activation. Once combined, the CDK-cyclin complex is capable of ... Herbst EA, MacPherson RE, LeBlanc PJ, Roy BD, Jeoung NH, Harris RA, Peters SJ (Jan 2014). "Pyruvate dehydrogenase kinase-4 ...
Like all cyclin family members, cyclin E forms a complex with cyclin-dependent kinase (CDK2). Cyclin E/CDK2 regulates multiple ... Cyclin E is a member of the cyclin family. Cyclin E binds to G1 phase Cdk2, which is required for the transition from G1 to S ... Morris L, Allen KE, La Thangue NB (April 2000). "Regulation of E2F transcription by cyclin E-Cdk2 kinase mediated through p300/ ... Cyclin E/CDK2 plays a critical role in the G1 phase and in the G1-S phase transition. Cyclin E/CDK2 phosphorylates ...
cyclin binding. • cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine ... CDKN1A, CAP20, CDKN1, CIP1, MDA-6, P21, SDI1, WAF1, p21CIP1, cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase ... cyclin-dependent protein kinase holoenzyme complex. • PCNA-p21 complex. • perinuclear region of cytoplasm. • клітинне ядро. • ... negative regulation of cyclin-dependent protein kinase activity. • transcription initiation from RNA polymerase II promoter. • ...
SLBP are marked for degradation by phosphorylation at two threonine residues by cyclin dependent kinases, possibly cyclin A/ ... "NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription". Genes & Development. 14 (18): ... The mitotic kinase aurora B phosphorylates histone H3 at serine 10, triggering a cascade of changes that mediate mitotic ... NPAT activates histone gene expression only after it has been phosphorylated by the G1/S-Cdk cyclin E-Cdk2 in early S phase.[ ...
Brooks, Gavin (2004). "Cyclins, Cyclin-Dependent Kinases, and Cyclin-Dependent Kinase Inhibitors: Detection Methods and ... Cyclins and cyclin-dependent kinases (CDK) are major positive regulators, and appear throughout the cell cycle. The CDK appear ... The CDK detects the presence of these cyclins by binding with these cyclins and produce a type of target protein to move the ... Once the cyclins are absent, it means the previous process in cell cycle is not finished yet, and hence the cell cycle comes to ...
Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which ... Simone C, Giordano A (2007). "Abrogation of signal-dependent activation of the cdk9/cyclin T2a complex in human RD ... This cyclin and its kinase partner CDK9 were found to be subunits of the transcription elongation factor p-TEFb. The p-TEFb ... "MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner". Mol. Cell. Biol. 23 (14): 4859-69 ...
The cell cycle is regulated by a series of signalling factors and complexes such as cyclin-dependent kinases and p53, to name a ... 3] The theory also states that both plants and animals are composed of cells which was confirmed by plant scientist, Matthias ...
Li Y, Jenkins CW, Nichols MA, Xiong Y. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. „ ... The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. „Cell". 75 (4), s. 805-816, 1993. ... a b Entrez Gene: CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1). ... Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell ...
Cell cycle progression is controlled by ordered action of cyclin-dependent kinases (CDKs), activated by specific cyclins that ... is one of the 19S subcomponents that also tightly binds the cyclin-dependent kinase CDK4 and plays a key role in recognizing ... In particular, exit from mitosis requires the proteasome-dependent dissociation of the regulatory component cyclin B from the ... the ATP-dependent proteolytic complex that was responsible for ubiquitin-dependent protein degradation was discovered and was ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ...
... preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase ... Linalol (3,7-dimetylooktadi-1,6-en-3-ol) - organiczny związek chemiczny, nienasycony alkohol alifatyczny, należący do grupy ... Basic Clin Pharmacol Toxicol". 113 (3), s. 167-172, 2013. DOI: 10.1111/bcpt.12087. PMID: 23692366. ... InChI=1S/C10H18O/c1-5-10(4,11)8-6-7-9(2)3/h5,7,11H,1,6,8H2,2-4H3 ...
All these phases in the cell cycle are highly regulated by cyclins, cyclin-dependent kinases, and other cell cycle proteins. ... Generation of pressure is dependent on formin-mediated F-actin nucleation[71] and Rho kinase (ROCK)-mediated myosin II ... This can occur when cells become overcrowded (density-dependent inhibition) or when they differentiate to carry out specific ... Ramanathan SP, Helenius J, Stewart MP, Cattin CJ, Hyman AA, Muller DJ (February 2015). "Cdk1-dependent mitotic enrichment of ...
... endothelin receptor A and cyclin dependent kinase inhibitor. Mutations in interleukin 6 may be protective.[citation needed]. ... 74 (3): 564-571. doi:10.1086/382285. PMC 1182270 . PMID 14872410.. *^ a b c d Haberland, Catherine (2007). Clinical ... ISBN 1-4051-1551-3.. *^ a b White, Philip M.; Teasdale, Evelyn M.; Wardlaw, Joanna M.; Easton, Valerie (2001-06-01). " ... 2010 May-June; 34(3):440-445.. *^ Brilstra, E. H.; Rinkel, G. J. E.; van der Graaf, Y.; van Rooij, W. J. J.; Algra, A. (1 ...
"CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle progression". Cell. 151 (6): 1308-18. doi: ... "The turn motif is a phosphorylation switch that regulates the binding of Hsp70 to protein kinase C". The Journal of Biological ... 978-3-319-11730-0. . PMID 25487014.. *^ Wegele H, Müller L, Buchner J (2004). Hsp70 and Hsp90 - a relay team for protein ... 978-3-540-22096-1. . PMID 14740253.. *^ Cvoro A, Dundjerski J, Trajković D, Matić G (1999-04-01). "The level and ...
Jiang MC, Liao CF, Tai CC (June 2002). "CAS/CSE 1 stimulates E-cadhrin-dependent cell polarity in HT-29 human colon epithelial ... "Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes". The Journal of Cell Biology. 128 (5): ... Laoukili J, Alvarez-Fernandez M, Stahl M, Medema RH (September 2008). "FoxM1 is degraded at mitotic exit in a Cdh1-dependent ... The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein composed of five extracellular cadherin repeats, a ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... 1omw: Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and ... Buhl AM, Osawa S, Johnson GL (1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human ... 2bcj: Crystal Structure of G Protein-Coupled Receptor Kinase 2 in Complex with Galpha-q and Gbetagamma Subunits ...
Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bad (a Bcl-2 ... Caspases are proteins that are highly conserved, cysteine-dependent aspartate-specific proteases. There are two types of ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... the protein is cleaved by a calcium-dependent calpain protease ... 54 (3): 185-92. doi:10.1530/JME-14-0327. PMID 25791374.. *^ a b Jan R, Chaudhry G (2019). "Understanding Apoptosis and ...
November 1999). "Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q ... Mantle cell lymphoma is excluded due to the lack of CD5 and cyclin-D1 expression. Clonal rearrangements of the immunoglobulin ... July 1998). "Absence of cyclin D1 protein expression in splenic marginal zone lymphoma". Mod. Pathol. 11 (7): 601-6. PMID ... 3. Lyon: IARC Press. ISBN 92-832-2411-6. CS1 maint: Multiple names: authors list (link) Melo JV, Hegde U, Parreira A, Thompson ...
GTP-dependent protein binding. • GTPase activity. • mitogen-activated protein kinase kinase kinase binding. • protein binding. ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... "The MAP kinase kinase kinase MLK2 co-localizes with activated ... protein kinase binding. • nucleotide binding. • GTP binding. • identical protein binding. Cellular component. • cytoplasm. • ... regulation of protein kinase activity. • regulation of attachment of spindle microtubules to kinetochore. • regulation of small ...
... and the cyclin dependent kinase inhibitors P27 and P21.». Leuk. Lymphoma 43 (1): 51-7. PMID 11908736. doi:10.1080/ ... de 2000). «Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of ... Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation». J ... doi:10.1016/S1286-4579(99)00254-3. *↑ Ebner, R; Chen R H, Lawler S, Zioncheck T, Derynck R (Nov. de 1993). «Determination of ...
... cyclins and cyclin dependent kinases". Oncogene. 15 (2): 143-57. doi:10.1038/sj.onc.1201252. PMID 9244350.. ... "BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site". Mol. Cell. Biol. 19 (7): ... "BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3". ... kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment ...
Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P (March 2001). "Amphiphysin 1 binds the cyclin-dependent kinase ... Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P (March 2001). "Amphiphysin 1 binds the cyclin-dependent kinase ... Chen-Hwang MC, Chen HR, Elzinga M, Hwang YW (May 2002). "Dynamin is a minibrain kinase/dual specificity Yak1-related kinase 1A ... Micheva KD, Ramjaun AR, Kay BK, McPherson PS (September 1997). "SH3 domain-dependent interactions of endophilin with ...
... phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase ... 3% berupa subtipe B, 5.3% adalah subtipe D dan 3.2% merupakan CRF AE, sedangkan sisanya berasal dari subtipe dan CRF lain.[12] ... 3-5%).[25] Hal ini pun dapat dicegah dengan melakukan pemeriksaan produk darah dan transplan sebelum didonorkan dan menghindari ... 3] Indonesia adalah negara ketiga di dunia yang memiliki penderita HIV terbanyak yaitu sebanyak 640.000 orang, setelah China ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... Gαs activates the cAMP-dependent pathway by stimulating the production of cyclic AMP (cAMP) from ATP. This is accomplished by ... The cAMP-dependent pathway is used as a signal transduction pathway for many hormones including:. *ADH - Promotes water ... cAMP can then act as a second messenger that goes on to interact with and activate protein kinase A (PKA). PKA can ...
These transitions are controlled by the cyclin-dependent kinase Cdk1.[6] Though the proteins that control Cdk1 are well ... a cyclin-dependent kinase, on a tyrosine residue. Cdc2 drives entry into mitosis by phosphorylating a wide range of targets. ... The protein kinase Cdr2 (which negatively regulates Wee1) and the Cdr2-related kinase Cdr1 (which directly phosphorylates and ... Wu L, Russell P (June 1993). "Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase". Nature. 363 (6431): 738-41. ...
The process follows fertilization, with the transfer being triggered by the activation of a cyclin-dependent kinase complex.[1] ... high levels of proteins that control cell cycle progression such as the cyclins and their associated cyclin-dependent kinases ( ... cdk). The complex Cyclin B/CDK1 a.k.a. MPF (maturation promoting factor) promotes entry into mitosis. ... 3] These holoblastic cleavage planes pass all the way through isolecithal zygotes during the process of cytokinesis. ...
CDK抑制因子(英语:Cyclin-dependent kinase inhibitor protein). *INK4a/ARF(p14arf/p16、p15、p18、p19) ... Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle. BioEssays. June 1995, 17 (6): 471-80. PMID ... 細胞週期的進行是由不同的週期素(Cyclin)所調控。週期素意味著這些蛋白質的表現量會隨著細胞週期的進行而有所變化,進而確認週期素原來是扮演細胞
Liu H, Di Cunto F, Imarisio S, Reid LM (Jan 2003). "Citron kinase is a cell cycle-dependent, nuclear protein required for G2/M ... Dephospho-(reductase kinase) kinase (EC *AMP-activated protein kinase α *PRKAA1 ... Myosin-heavy-chain kinase (EC *Aurora kinase *Aurora A kinase ... protein kinase activity. • PDZ domain binding. • SH3 domain binding. • scaffold protein binding. • metal ion binding. • kinase ...
CDK3/cyclin-C mediated RB1 phosphorylation is required for G0-G1 transition. Promotes G1-S transition probably by contributing ... Interacts with CCNC/cyclin-C during interphase. Phosphorylates histone H1, ATF1, RB1 and CABLES1. ATF1 phosphorylation triggers ... Serine/threonine-protein kinase that plays a critical role in the control of the eukaryotic cell cycle; involved in G0-G1 and ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR017441, Protein_kinase_ATP_BS. IPR008271, Ser/Thr_kinase_AS. ...
Cyclin-dependent kinase 12 increases 3 end processing of growth factor-induced c-FOS transcripts.. Eifler TT1, Shao W2, ... Transcriptional cyclin-dependent kinases (CDKs) regulate RNA polymerase II initiation and elongation as well as ... Cyclin-Dependent Kinase 12 Increases 3′ End Processing of Growth Factor-Induced c-FOS Transcripts ... Cyclin-Dependent Kinase 12 Increases 3′ End Processing of Growth Factor-Induced c-FOS Transcripts ...
Compounds targeting complexes between cyclin-dependent kinases (CDKs) and cyclins (Cy) and inhibiting their activity are ... Identification of potent pyrazolo[4,3-h]quinazoline-3-carboxamides as multi-cyclin-dependent kinase inhibitors.. Traquandi G1, ... An expansion of pyrazolo[4,3-h]quinazoline chemical class oriented to the development of three points of variability was ...
CYCLIN-DEPENDENT KINASE 2 (CDK2) COMPLEXED WITH 3-{[(2,2-DIOXIDO-1,3-DIHYDRO-2-BENZOTHIEN-5-YL)AMINO]METHYLENE}-5-(1,3-OXAZOL-5 ... Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray ... were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepared as a homologue of the 3 ... were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepa ... ...
HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR 3-[4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino]-phenol. *DOI ... pyrimidin-2-ylamines as moderately potent inhibitors of cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analogue program was ... pyrimidin-2-ylamines as moderately potent inhibitors of cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analogue program was ... Cell division protein kinase 2. A. 298. Homo sapiens. Mutation(s): 0 Gene Names: CDK2, CDKN2. EC: 2.7.1 (PDB Primary Data), 2.7 ...
What is Cyclin-dependent Kinase-like 3? Meaning of Cyclin-dependent Kinase-like 3 medical term. What does Cyclin-dependent ... Looking for online definition of Cyclin-dependent Kinase-like 3 in the Medical Dictionary? Cyclin-dependent Kinase-like 3 ... redirected from Cyclin-dependent Kinase-like 3). Also found in: Acronyms. CDKL3. A gene on chromosome 5q31 that encodes a CMGC- ... Cyclin-Dependent Kinase-Like 5. *Cyclin-dependent kinases. *Cyclin-dependent kinases. *cyclin-dependent kinases 4 and 6 binding ...
... serine threonine protein kinase NKIAMRE; CDKL3 protein; Cyclin dependent kinase like 3; serine-threonine protein kinase NKIAMRE ... The protein encoded by this gene is a member of cyclin-dependent protein kinase (CDK) family. CDK family members are highly ... Profiling ServicesKinase Screening & Profiling ServicesIon Channel Screening & Profiling ServicesGPCR Screening & Profiling ... CDKL3; cyclin-dependent kinase-like 3; NKIAMRE; ...
Effects of Glycogen Synthase Kinase 3β and Cyclin-Dependent Kinase 5 Inhibitors on Morphine-Induced Analgesia and Tolerance in ... Effects of Glycogen Synthase Kinase 3β and Cyclin-Dependent Kinase 5 Inhibitors on Morphine-Induced Analgesia and Tolerance in ... Effects of Glycogen Synthase Kinase 3β and Cyclin-Dependent Kinase 5 Inhibitors on Morphine-Induced Analgesia and Tolerance in ... Effects of Glycogen Synthase Kinase 3β and Cyclin-Dependent Kinase 5 Inhibitors on Morphine-Induced Analgesia and Tolerance in ...
... Br J Cancer. ... an oral cyclin-dependent kinase 4/6 inhibitor with potent anti-proliferative activity in vitro/vivo. ...
... cyclin-dependent kinase inhibitor 2A / p16INK4a (isoform 3) in the Antibody Database ... p16 / CDKN2A / cyclin-dependent kinase inhibitor 2A / p16INK4a (isoform 3) Antibodies by Conjugate. ... Fluorochrome conjugates for (p16 / CDKN2A / cyclin-dependent kinase inhibitor 2A / p16INK4a (isoform 3)) in the Chromocyte ...
Zhang, B., Tan, V.B.C., Lim, K.M., Tay, T.E., Zhuang, S. (2007-01). Study of the inhibition of cyclin-dependent kinases with ... Study of the inhibition of cyclin-dependent kinases with roscovitine and indirubin-3′-oxime from molecular dynamics simulations ... the stronger affinity for the R enantiomer is the presence of an important hydrogen bond between R-roscovitine and the kinases ... The simulations detected the displacement of a water molecule in the active site of the water-included CDK/indirubin-3′-oxime ...
2002). "ik3-1/Cables is a substrate for cyclin-dependent kinase 3 (cdk 3)". Eur. J. Biochem. 268 (23): 6076-82. doi:10.1046/j. ... Meikrantz W, Schlegel R (1996). "Suppression of apoptosis by dominant negative mutants of cyclin-dependent protein kinases". J ... Dephospho-(reductase kinase) kinase (EC *AMP-activated protein kinase α *PRKAA1 ... Myosin-heavy-chain kinase (EC *Aurora kinase *Aurora A kinase ...
... cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene. 1995;11211-9. ... Cyclin E is the only cyclin-dependent kinase 2-associated cyclin that predicts metastasis and survival in early stage non-small ... A cyclin D1/cyclin-dependent kinase 4 binding site within the C domain of the retinoblastoma protein. Cancer Res. 2001;61:2885- ... Pines J. Cyclins and cyclin-dependent kinases: take your partners. Trends Biochem Sci. 1993;18:195-7. ...
Serine/threonine-protein kinase that acts like an antiapoptotic protein that counters TRAIL/TNFSF10-induced apoptosis by ... IPR011009 Kinase-like_dom_sf. IPR000719 Prot_kinase_dom. IPR017441 Protein_kinase_ATP_BS. IPR008271 Ser/Thr_kinase_AS. ... Cyclin-dependent kinase 15 (EC: Publication. Manual assertion based on experiment ini ... sp,Q96Q40,CDK15_HUMAN Cyclin-dependent kinase 15 OS=Homo sapiens OX=9606 GN=CDK15 PE=1 SV=2 ...
ProteoGenix provides you the best Kinases proteins. Shop now from our 200 000 + products. ... Buy online Recombinant Human cyclin-dependent kinase 3 Protein from Prospec cat# pka-055. ... More info about Recombinant Human cyclin-dependent kinase 3 Protein. Catalog#: pka-055. ... Data sheet of Recombinant Human cyclin-dependent kinase 3 Protein. Brand. Prospec. ...
It was identified as a cyclin-dependent kinase inhibitor, and has been shown to interact with, and dephosphorylate CDK2 kinase ... cyclin dependent kinase inhibitor 3. Enable Javascript to view the expand/collapse boxes.. Open All Close All ... thus prevent the activation of CDK2 kinase. This gene was reported to be deleted, mutated, or overexpressed in several kinds of ...
Cyclin Dependent Kinase 3, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human ... protein serine/threonine kinase activity. IEA. --. GO:0004693. cyclin-dependent protein serine/threonine kinase activity. IBA, ... ik3-1/Cables is a substrate for cyclin-dependent kinase 3 (cdk 3). (PMID: 11733001) Yamochi T … Matsuoka M (European journal of ... cyclin dependent kinase 3,involved in cell cycle regulation (G1 to S transition),not complexing with any cyclin *CDK3 ...
Evidence for different mode of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinase, p21 and p27 bind to ... Mechanism for Inactivation of the KIP Family Cyclin-dependent Kinase Inhibitor Genes in Gastric Cancer Cells. Jong-Yeon Shin, ... Margarita S. B., Ana I. S., Juan C. M., Mateo M. S., Lydia S. V., Raquel V., Giancarlo T., Miguel A. P. Cyclin-dependent kinase ... Sherr C. J., Roberts J. M. Inhibitors of mammalian G1 cyclin-dependent kinase. Genes Dev., 9: 1149-1163, 1995. ...
Cyclin Dependent Kinase Inhibitor 3, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards ... It was identified as a cyclin-dependent kinase inhibitor, and has been shown to interact with, and dephosphorylate CDK2 kinase ... Binding of HTm4 to cyclin-dependent kinase (Cdk)-associated phosphatase (KAP).Cdk2.cyclin A complex enhances the phosphatase ... regulation of cyclin-dependent protein serine/threonine kinase activity. TAS. 8242750. GO:0000082. G1/S transition of mitotic ...
CRYSTAL STRUCTURE OF KINASE ASSOCIATED PHOSPHATASE (KAP) IN COMPLEX WITH PHOSPHO-CDK2 ... CYCLIN-DEPENDENT KINASE INHIBITOR 3: A. CELL DIVISION PROTEIN KINASE 2: B. SMTL:PDB. SMTL Chain Id:. PDB Chain Id:. A. A ... CRYSTAL STRUCTURE OF KINASE ASSOCIATED PHOSPHATASE (KAP) IN COMPLEX WITH PHOSPHO-CDK2. Coordinates. PDB Format Method. X-RAY ... Song, H. et al., Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in ...
... pyrimidine derivatives as cycline dependent kinase inhibitors (CDKIs). Moreover, cytotoxic activity for the newly synthesized ... Pyrazolopyrimidine derivatives as cyclin-dependant kinase inhibitors, 978-3-659-79299-1, This book contains both review and ... Pyrazolopyrimidine derivatives as cyclin-dependant kinase inhibitors. LAP LAMBERT Academic Publishing (2016-02-26 ) ... pyrimidine derivatives as cycline dependent kinase inhibitors (CDKIs). Moreover, cytotoxic activity for the newly synthesized ...
Molecular cloning of a cyclin-like protein associated with cyclin-dependent kinase 3 (cdk 3) in vivo. In: Biochemical and ... Molecular cloning of a cyclin-like protein associated with cyclin-dependent kinase 3 (cdk 3) in vivo. / Matsuoka, Masaaki; ... title = "Molecular cloning of a cyclin-like protein associated with cyclin-dependent kinase 3 (cdk 3) in vivo", ... T1 - Molecular cloning of a cyclin-like protein associated with cyclin-dependent kinase 3 (cdk 3) in vivo ...
keywords = "Alzheimers disease, Cyclin-dependent kinases, Glycogen synthase kinase, Hymenialdisine, Tau",. author = "L. Meijer ... The marine sponge constituent hymenialdisine is a potent inhibitor of cyclin-dependent kinases, glycogen synthase kinase-3β and ... The marine sponge constituent hymenialdisine is a potent inhibitor of cyclin-dependent kinases, glycogen synthase kinase-3β and ... The marine sponge constituent hymenialdisine is a potent inhibitor of cyclin-dependent kinases, glycogen synthase kinase-3β and ...
... and sub-groups thereof are inhibitors of cyclin dependent kinases, and in particular cyclin dependent kinases selected from ... The activity of the compounds of the invention as inhibitors of cyclin dependent kinases and glycogen synthase kinase-3 can be ... or inhibit cell proliferation through the inhibition of protein kinases such as cyclin dependent kinase or tyrosine kinase. The ... 4-DISUBSTITUTED 1H-PYRAZOLE COMPOUNDS AND THEIR USE AS CYCLIN DEPENDENT KINASES (CDK) AND GLYCOGEN SYNTHASE KINASE-3 (GSK-3) ...
Cyclin-dependent kinase 11 (CDK11; also named PITSLRE) is part of the large family of p34cdc2-related kinases whose functions ... N2 - Cyclin-dependent kinase 11 (CDK11; also named PITSLRE) is part of the large family of p34cdc2-related kinases whose ... AB - Cyclin-dependent kinase 11 (CDK11; also named PITSLRE) is part of the large family of p34cdc2-related kinases whose ... abstract = "Cyclin-dependent kinase 11 (CDK11; also named PITSLRE) is part of the large family of p34cdc2-related kinases whose ...
Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor-positive (ER+) breast cancer. This ... N2 - Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor-positive (ER+) breast cancer. ... AB - Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor-positive (ER+) breast cancer. ... abstract = "Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor-positive (ER+) breast ...
Pines J. Cyclins and cyclin-dependent kinases: theme and variations. Adv. Cancer Res., 66: 181-212, 1995. ... Wang Z., Su Z. Z., Fisher P. B., Wang S., Van Tuyle G., Grant S. Evidence of a functional role for the cyclin-dependent kinase ... Sherr C. J., Roberts J. M. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev., 9: 1149-1163, 1995. ... Senderowicz A. M. Flavopiridol: the first cyclin-dependent kinase inhibitor in human clinical trials. Invest. New Drugs, 17: ...
Cyclin-dependent kinase inhibitor 3. CDK1and CDK2 inhibitor. −0.428. GC35573. U20979. CHAF1A. Chromatin assembly factor 1, ... Krystof, V.; Uldrijan, S. Cyclin-dependent kinase inhibitors as anticancer drugs. Curr. Drug Targets 2010, 11, 291-302. [Google ... Molecular docking was performed to calculate the interaction energy and geometry of scopoletin with I-κB kinase β, I-κB kinase ... I-κB kinase β (PDB ID:3RZF), I-κB kinase β-NEMO complex (PDB ID: 3BRT), NF-κB (p52/RelB heterodimer, PDB ID: 3DO7), NF-κB-DNA ...
Table 1: Total Pipeline Products for Cyclin-Dependent Kinase 9 (CDK9) Inhibitor. Table 2: Cyclin-Dependent Kinase 9 (CDK9) ... Figures 1: Total Products for Cyclin-Dependent Kinase 9 (CDK9) Inhibitor. Figure 2: Cyclin-Dependent Kinase 9 (CDK9) Inhibitor ... Cyclin Dependent Kinase 4 (Cell Division Protein Kinase 4 or PSK J3 or CDK4 or EC - Pipeline Review, H1 2018 * Drug ... Cyclin-Dependent Kinase 6 (Cell Division Protein Kinase 6 or EC - Pipeline Review, H1 2016 * Drug Pipelines ...
Human cyclin-dependent kinase 2 is activated during the S and G2 phases of the cell cycle and associates with cyclin A. ... has been shown to interact with several cyclin-dependent kinase complexes and block the activity of G1 cyclin-dependent kinases ... T-loop deletion of CDC2 from breast cancer tissues eliminates binding to cyclin B1 and cyclin-dependent kinase inhibitor p21. ... associated kinase activity was correlated with the appearance of complexes containing cyclin E and the cyclin-dependent kinase ...
  • Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). (
  • Following the identification through virtual screening of 4-(2,4-dimethyl-thiazol-5-yl)pyrimidin-2-ylamines as moderately potent inhibitors of cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analogue program was initiated. (
  • Using this knowledge, a structure-based design approach directed this chemical scaffold toward generating potent and selective CDK2 inhibitors, which selectively inhibited the CDK2-dependent phosphorylation of Rb and induced caspase-3-dependent apoptosis in HCT 116 tumor cells. (
  • Much of this binding specificity comes from the cyclin partner for CDK2, either cyclin E or cyclin A, which is required for catalytic activity ( 19 ). (
  • Moreover, we report the identification of structural features required for kinase inhibition, co-crystal structures of CDK2 in complex with initial leads, and evidence for a selective inhibition of CDK2 in tumor cells. (
  • It was identified as a cyclin-dependent kinase inhibitor, and has been shown to interact with, and dephosphorylate CDK2 kinase, thus prevent the activation of CDK2 kinase. (
  • Dephosphorylates CDK2 at 'Thr-160' in a cyclin-dependent manner. (
  • Interacts with cyclin-dependent kinases such as CDK1, CDK2 and CDK3. (
  • The CDK4/6-cyclin-D and CDK2-cyclin-E complexes are active in G1, and CDK2-cyclin-A and CDK1-cyclin-A are active in S phase. (
  • RB is sequentially phosphorylated by CDK4/6-cyclin-D and CDK2-cyclin-E complexes. (
  • Deregulation of CDK2 activity frequently results from the alteration in the expression levels of its regulators cyclin E and KIP1. (
  • Baumann K, Mandelkow E-M, Biernat J, Piwnica-Worms H, Mandelkow E. Abnormal Alzheimer-like phosphorylation of tau-protein by cyclin-dependent kinases cdk2 and cdk5. (
  • The activation of cyclin-dependent kinases (CDKs) requires the phosphorylation of a conserved threonine (Thr 160 in Cdk2) by CDK-activating kinase (CAK). (
  • The binding of cyclin A to Cdk2 inhibited the dephosphorylation of Thr 160 by KAP but did not preclude the binding of KAP to the cyclin A-Cdk2 complex. (
  • Moreover, the dephosphorylation of Thr 160 by KAP prevented Cdk2 kinase activity upon subsequent association with cyclin A. These results suggest that KAP binds to Cdk2 and dephosphorylates Thr 160 when the associated cyclin subunit is degraded or dissociates. (
  • Two such proteins, cyclin-dependent kinase-2 (Cdk2) and its downstream target, the retinoblastoma gene product (Rb), also play a critical role in the control of apoptosis. (
  • CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. (
  • Cyclin A is also produced, which binds to CDK2 and stimulates DNA replication. (
  • Transcriptional cyclin-dependent kinases (CDKs) regulate RNA polymerase II initiation and elongation as well as cotranscriptional mRNA processing. (
  • Compounds targeting complexes between cyclin-dependent kinases (CDKs) and cyclins (Cy) and inhibiting their activity are regarded as promising antitumor agents to complement the existing therapies. (
  • An expansion of pyrazolo[4,3-h]quinazoline chemical class oriented to the development of three points of variability was undertaken leading to a series of compounds able to inhibit CDKs both in vitro and in vivo. (
  • Cyclin-dependent kinases (CDKs) and their cyclin partners are key players in regulating the entry into, passage through, and exit from the cell cycle ( 1 -8 ). (
  • The process of eukaryotic cell division may be broadly divided into a series of sequential phases termed Gl, S, G2 and M. Correct progression through the various phases of the cell cycle has been shown to be critically dependent upon the spatial and temporal regulation of a family of proteins known as cyclin dependent kinases (CDKs) and a diverse set of their cognate protein partners termed cyclins. (
  • CDKs are cdc2 (also known as CDKl) homologous serine-threonine kinase proteins that are able to utilise ATP as a substrate in the phosphorylation of diverse polypeptides in a sequence dependent context. (
  • Modulation of the expression levels, degradation rates, and activation levels of various CDKs and cyclins throughout the cell cycle leads to the cyclical formation of a series of CDK/cyclin complexes, in which the CDKs are enzymatically active. (
  • 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 ). (
  • The cell cycle is regulated by cyclin-dependent kinases (CDKs), which form active heterodimeric kinases when bound to the cyclins. (
  • Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (
  • More than 10 years ago, the discovery of cyclin-dependent ki- nases (Cdks) ushered in a new era in the understanding of cell proliferation and its control. (
  • For example, although Cdks appear to be highly conserved phylogenetically, cyclins are much less so. (
  • These cyclins oscillate, increasing and decreasing at different stages, binding to CDKs and driving the cell cycle forward. (
  • In addition to cyclin levels, this provides and additional way to control the activity of CDKs. (
  • 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. (
  • We have identified a new structural class of protein serine/threonine kinase inhibitors comprising an aminoimidazo[1,2- a ]pyridine nucleus. (
  • Although considerable efforts are still devoted to these chemical families and their structurally related analogues, the identification of new structural classes of protein serine/threonine kinase inhibitors remains highly desirable. (
  • Herein we report that the aminoimidazo[1,2- a ]pyridine scaffold represents a new structural class of protein serine/threonine kinase inhibitors. (
  • Predicted to have cyclin-dependent protein serine/threonine kinase activity. (
  • Cyclin-dependent kinases (CDK) are serine/threonine kinases that are activated upon association with cyclin proteins to form CDK complexes. (
  • Here, we use primary cultures of rat hippocampal neurons to show that elevated neuronal activity impairs phosphorylation of the serine/threonine kinase, Erk1/2, and the activation of signal transducer and activator of transcription 3 (STAT3) by phosphorylation of serine 727. (
  • Chronically stimulated neurons go through apoptosis when they fail to activate another serine/threonine kinase, Akt. (
  • Glycogen synthase kinase 3, or GSK-3, is a serine/threonine, proline-directed kinase involved in a diverse array of signaling pathways, including glycogen synthesis and cellular adhesion. (
  • Cyclin Dependent Kinase 7 (39 kDa Protein Kinase or CDK Activating Kinase 1 or Cell Division Protein Kinase 7 or TFIIH Basal Transcription Factor Complex Kinase Subunit or Serine/Threonine Protein Kinase 1 or CDK7 or EC or EC - Cell division protein kinase 7 is an enzyme that in humans is encoded by the CDK7 gene. (
  • Cyclin Dependent Kinase 7 (39 kDa Protein Kinase or CDK Activating Kinase 1 or Cell Division Protein Kinase 7 or TFIIH Basal Transcription Factor Complex Kinase Subunit or Serine/Threonine Protein Kinase 1 or CDK7 or EC or EC pipeline Target constitutes close to 11 molecules. (
  • Cyclin-dependent kinases are a type of serine/threonine kinase which are activated by cyclins to drive the progress of the cell cycle. (
  • Once bound to a cyclin they act to phosphorylate many target proteins on serine or threonine amino acid residues. (
  • CDK3/cyclin-C mediated RB1 phosphorylation is required for G0-G1 transition. (
  • Cell division protein kinase 3 is an enzyme that in humans is encoded by the CDK3 gene . (
  • CDK3 can phosphorylate histone H1 and interacts with an unknown type of cyclin . (
  • CDK3 (Cyclin Dependent Kinase 3) is a Protein Coding gene. (
  • cdk3 has been considered to be rate-limiting for cell cycle progression of mammalian cells while its precise function remains to be elucidated, To assess cdk3 function, a cDNA coding for a cyclin-like protein (designated as ik3-1 from an interactor-1 with cdk3) was isolated with the yeast two-hybrid system using a cyclin-dependent kinase 3 (cdk3) cDNA as bait. (
  • This kinase was found in the exon junction complexes (EJC) together with SR proteins and was thus recruited to RNA polymerase II. (
  • Anti-HA antibodies immunoprecipitated HA epitope-tagged SRSF4 (lanes 4 and 8), SRSF5 (lanes 2 and 6), and SRSF6 (lanes 3 and 7) (h:SRSF) proteins from HEK293T cells (lower panels). (
  • Cyclins are a family of proteins characterised by a homology region, containing approximately 100 amino acids, termed the "cyclin box" which is used in binding to, and defining selectivity for, specific CDK partner proteins. (
  • 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. (
  • In recent years, many orthologues of the Snail family have been identified throughout the animal kingdom, and their study is providing new clues about the EMT-dependent and -independent functions of Snail proteins. (
  • Active CDK-cyclin complexes can be negatively regulated by two families of inhibitors, the INK4 and the WAF1/KIP proteins. (
  • Receptor-like kinases (RLKs) are a family of transmembrane proteins with versatile N-terminal extracellular domains and C-terminal intracellular kinases. (
  • GSK-3 phosphorylates Tau proteins and it is thought that miscues in GSK-3 signaling may contribute to the onset of Alzheimer's disease. (
  • GSK-3 beta Inhibitors offered by Santa Cruz inhibit GSK-3 beta and, in some cases, other cell signaling and Alzheimer's disease related proteins. (
  • Cdk9 interacts adversely with Gq-dependent pathways for hypertrophy, impairing the expression of numerous genes for mitochondrial proteins, and, in particular, suppressing master regulators of mitochondrial biogenesis and function, perioxisome proliferator-activated receptor-γ coactivator-1 (PGC-1), and nuclear respiratory factor-1 (NRF-1). (
  • 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. (
  • STAT proteins were recognized initially as transcription factors that were involved in expressions of specific genes, but not required for cell proliferation ( 3 , 14 ). (
  • Coexposure to FP also resulted in a more pronounced and sustained activation of the mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase cascade after PMA treatment, although disruption of this pathway by the mitogen-activated protein kinase kinase 1 inhibitor U0126 did not prevent potentiation of apoptosis. (
  • The protein encoded by this gene is a member of cyclin-dependent protein kinase (CDK) family. (
  • Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity . (
  • The mechanism for inactivation of the KIP family cyclin-dependent kinase inhibitor (CDKI) genes, the p21 , p27 , and p57 genes, in gastric cancer cells was tested by treating the cells with either the DNA demethylation agent, 5-aza-2′-deoxycytidine or the histone deacetylase inhibitor, n -butyric acid or trichostatin A. RNA expression of the gene was determined by reverse transcription PCR. (
  • Purified recombinant CDK11 p46 inhibited translation of a reporter gene in vitro in a dose-dependent manner. (
  • In contrast, a kinase-defective mutant CDK11 p46M did not inhibit translation of the reporter gene. (
  • Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene . (
  • The protein encoded by this gene is a member of the Ser/Thr protein kinase family . (
  • This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product ( Rb ). (
  • Cell division protein kinase 8 is an enzyme that in humans is encoded by the CDK8 gene . (
  • Another example of structural variability is seen in vertebrates, in which 3 paralogues of subunits of the cyclin-dependent kinase module have evolved by 3 independent gene duplication events followed by sequence divergence. (
  • In human tumors, ERK activation occurs as a result of receptor tyrosine kinase (RTK) activation or mutations in members of the RAS and RAF gene families ( 1 , 2 ). (
  • Interestingly, this gene family constitutes 60% of all kinases in Arabidopsis and accounts for nearly all transmembrane kinases in Arabidopsis. (
  • The diversity of domain organization and large gene number in this family suggest that domain fusion contributed to the formation of novel receptor kinases, and subsequent gene duplications resulted in the expansion of the RLK/Pelle subfamilies in plants. (
  • We have previously demonstrated that loss of one candidate gene at this locus, cyclin-dependent kinase inhibitor 2B (Cdkn2b), in mice promotes vascular SMC apoptosis and aneurysm progression. (
  • The protein encoded by this gene belongs to the cdc2/cdkx subfamily of the ser/thr family of protein kinases. (
  • Gene expression peaked on day 3 , and the functional cluster "inflammation" contained the greatest number of genes. (
  • 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. (
  • The RV-cyclin increases CDK8 occupancy at the EGR1 gene locus before and after serum stimulation. (
  • 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. (
  • 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. (
  • Initially, a mitogenic stimulus leads to the upregulation of cyclin D gene expression, which binds to CDK4. (
  • Hymenialdisine inhibits CDK5/p35 in vivo as demonstrated by the lack of phosphorylation/down-regulation of Pak1 kinase in E18 rat cortical neurons, and also inhibits GSK-3 in vivo as shown by the inhibition of MAP-1 B phosphorylation. (
  • Fig. 5: Aurora kinase co-inhibition durably suppresses mTORC1 signaling and alters the BAX/BCL2 ratio. (
  • mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. (
  • Klempner, S. J., Myers, A. P. & Cantley, L. C. What a tangled web we weave: emerging resistance mechanisms to inhibition of the phosphoinositide 3-kinase pathway. (
  • The mitogen-activated protein kinase, extracellular signal-regulated kinase kinase (MEK)/ERK-dependent transcriptional output was defined as the genes whose expression changes significantly 8 h after MEK inhibition. (
  • Also displays potent and selective inhibition of GSK-3β (IC 50 values are 40 and 4 nM respectively). (
  • Experimental evidence suggests that inhibition of cyclin D-dependent kinase activity may prevent tumor growth and/or at least partially revert the transformed phenotype. (
  • For example, reduction of cyclin D expression through antisense technology causes a concomitant decline in cyclin D-dependent kinase activity and results in inhibition of tumor growth, abolition of tumorigenicity, or, in some instances, tumor cell death ( 24 -27 ). (
  • Inhibition of tau phosphorylating protein kinase cdk5 prevents β-amyloid-induced neuronal death. (
  • Tau phosphorylation proceeds to tau aggregation that is favored by kinases like glucose-synthase kinase-3 β (GSK-3 β ) [ 11 ], while inhibition of GSK-3 β activity prevented not only tau phosphorylation but also tau aggregation in hippocampus [ 12 ]. (
  • 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. (
  • Fry, et al, "Specific Inhibition of Cyclin-dependent Kinase 4/6 by PD 0332991 and Associated Antitumor Activity in Human Tumor Xenografts," Molecular Cancer Therapeutics, Nov. 12, 2004 pp. 1427-1438, vol. 3. (
  • Eukaryotic cell cycle progression is governed by the sequential activation and inactivation of various cyclin/CDK 3 complexes. (
  • Cell proliferation is controlled at specific stages of the cell cycle by distinct protein kinase complexes. (
  • [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. (
  • Cyclin D-CDK4 complexes are major integrators of various mitogenic and antimitogenic signals. (
  • The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (
  • Asada A, Yamamoto N, Gohda M, Saito T, Hayashi N, Hisanaga S. Myristoylation of p39 and p35 is a determinant of cytoplasmic or nuclear localization of active cycline-dependent kinase 5 complexes. (
  • The CDK complex responsible for driving cells through mitosis is CDK1-cyclin B. (
  • When cyclin A activity is blocked by a peptide inhibitor, selective apoptosis is observed in cancer cells which do not retain a functional Rb protein ( 22 ). (
  • Failure to satisfy the pre-requisite biochemical criteria at a given cell cycle checkpoint, i.e. failure to form a required CDK/cyclin complex, can lead to cell cycle arrest and/or cellular apoptosis. (
  • Interactions between the cyclin-dependent kinase inhibitor (CDKI) flavopiridol (FP) and phorbol 12-myristate 13-acetate (PMA) were examined in U937 human leukemia cells in relation to differentiation and apoptosis. (
  • Small intermediates termed as "soluble oligomers" in the aggregation process may influence synaptic dysfunction, while large insoluble deposits might function as reservoirs of the bioactive oligomers that can lead to synaptic dysfunction, neuronal apoptosis, and brain damage [ 3 , 4 ]. (
  • It works by inhibiting cyclin-dependent kinases, arresting cell division and causing apoptosis in non-small lung cancer cells. (
  • The dose dependent behavior of LNCaP cells in response to ACCE was identified to process an Akt apoptosis pathway, in which Cyclin D1 activity and pRb phosphorylation were both down-regulated. (
  • In contrast, being without p53, PC3 cells showed a G2/M phase arrest mediated through the p21 proceed Cyclin B1/Cdc2 pathway, however, with limited number of cell apoptosis observed. (
  • These results demonstrate that Stat3 activation is involved in IL-6-dependent T cell proliferation through prevention of apoptosis independently of Bcl-2. (
  • Hymenialdisine also blocks the in vivo phosphorylation of the microtubule-binding protein tau at sites that are hyperphosphorylated by GSK-3 and CDK5/p35 in Alzheimer's disease (cross-reacting with Alzheimer's-specific AT100 antibodies). (
  • In this chapter, we discuss the activation mechanism of the CDK5 kinase within the general frame of reference of kinase activation mechanisms, and in comparison to other members of the CDK family. (
  • We explain how CDK5, not unlike other kinases, has made its own capricious decisions to design an original activation mechanism and distinguish itself from CDK-family relatives. (
  • Cyclin-dependent kinase 5 (cdk5) activation requires interaction with three domains of p35. (
  • A model of the complex between cyclin-dependent kinase 5 and the activation domain of neuronal Cdk5 activator. (
  • A Jekyll and Hyde kinase: roles for Cdk5 in brain development and disease. (
  • 1993 ). p35 (CDK5R1) was then characterized as a regulatory subunit of CDK5 to activate its kinase activity, with subsequent identification of its isoform p39 (CDK5R2) (Tsai et al. (
  • 1995 ). CDK5/p35 is the first example of a CDC2-like kinase with neuronal function. (
  • Cyclin-dependent kinase 5 (CDK5) controls melanoma cell motility, invasiveness, and metastatic spread-identification of a promising novel therapeutic target. (
  • Genetic alterations usually affect CDK4 and CDK6, their positive (mainly cyclin D1) and negative (INK4A and INK4B) regulators and their substrates (mainly RB). (
  • Meyerson, M. & Harlow, E. Identification of G1 kinase activity for cdk6, a novel cyclin D partner. (
  • PD 0332991 is a highly specific inhibitor of cyclin-dependent kinase 4 (Cdk4) (IC 50 , 0.011 μmol/L) and Cdk6 (IC 50 , 0.016 μmol/L), having no activity against a panel of 36 additional protein kinases. (
  • Progression through the G 1 -S phase requires phosphorylation of the retinoblastoma (Rb) protein by Cdk4 ( 7 , 8 ) or the highly homologous enzyme Cdk6 ( 9 , 10 ) in complex with their activating subunits, the D-type cyclins, D1, D2, or D3 ( 11 ). (
  • Cyclin-dependent kinase 6 (CDK6) bound to the inhibitor ribociclib (detail view). (
  • This invention relates to pyrazole compounds that inhibit or modulate the activity of cyclin dependent kinases (CDK) and glycogen synthase kinase-3 (GSK-3), to the use of the compounds in the treatment or prophylaxis of disease states or conditions mediated by cyclin dependent kinases and glycogen synthase kinase-3, and to novel compounds having cyclin dependent kinase or glycogen synthase kinase-3 inhibitory or modulating activity. (
  • Biochemicals that inhibit cyclin E have many applications in biochemical and physiological research. (
  • RV-cyclin does not increase activating phosphorylation events in the mitogen-activated protein kinase pathway and does not inhibit decay of IEG mRNAs. (
  • Molecular motions of human cyclin-dependent kinase 2. (
  • Recombinant Human Cyclin-Dependent Kinase Inhibitor 2A produced in E.coli is a single non-glycosylated polypeptide chain containing 156 amino acids and having a molecular mass of approximately 16.5 kDa. (
  • View detailed GSK-3 beta Inhibitor specifications, including GSK-3 beta Inhibitor CAS number, molecular weight, molecular formula and chemical structure, by clicking on the product name. (
  • A milestone in the history of human tumor immunology is certainly the molecular characterization of the first human melanoma Ag (MAGE) 3 recognized by T cells ( 1 ). (
  • This drug class inhibits one or more of the phosphoinositide 3-kinase enzymes, which are part of the PI3K/AKT/mTOR pathway, an important signalling pathway for many cellular functions such as growth control, metabolism and translation initiation. (
  • Orthologous to human CDKL3 (cyclin dependent kinase like 3). (
  • Detection limit for recombinant GST tagged CDKL3 is 3 ng/ml as a capture antibody. (
  • Long, Lin;He, Jian-Zhong;Chen, Ye;Xu, Xiu-E;Liao, Lian-Di;Xie, Yang-Min;Li, En-Min;Xu, Li-Yan 2018-05-07 00:00:00 Abstract Background Riboflavin is an essential component of the human diet and its derivative cofactors play an established role in oxidative metabolism. (
  • The appropriate protein kinase functions in signalling pathways to activate or inactivate (either directly or indirectly), for example, a metabolic enzyme, regulatory protein, receptor, cytoskeletal protein, ion channel or pump, or transcription factor. (
  • Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor-positive (ER + ) breast cancer. (
  • Tumors with mutant BRAF and those with receptor tyrosine kinase (RTK) activation have similar levels of phosphorylated ERK, but only the former depend on ERK signaling for proliferation. (
  • In addition, studies with the mutated erythropoietin receptor and the dominant negative Stat5 protein demonstrated that Stat5 is crucial for erythropoietin- and IL-3-dependent cell proliferation, respectively ( 15 , 16 , 17 ). (
  • Synthesis and Tyrosine Kinase Inhibitory Activity of a Series of 2- amino-8H-pyrido[2,3-d]pyrimidines: Identification of Potent, Selective Platelet-derived Growth Factor Receptor Tyrosine Kinase Inhibitors," Journal ofMedicinal Chemistry, Jul. (
  • Sex-dependent and -independent transcriptional changes during haploid phase gametogenesis in the sugar kelp Saccharina latissima. (
  • For example, after binding the enhancer and core promoter, the mediator complex undergoes a compositional change in which the kinase module dissociates from the complex to allow association with RNA polymerase II and transcriptional activation. (
  • evasion of this feedback in mutant BRAF cells is associated with increased transcriptional output and MEK/ERK-dependent transformation. (
  • The profile of genes dependent on MEK/ERK signaling for expression in V600E BRAF tumor cells includes transcription factors associated with ERK-dependent transformation, such as members of the ETS family, FOS and MYC. (
  • Key target genes in this process include master regulators of the cell cycle, such as cyclin E, which regulates G(1) progression, and cyclin A, which is required for the initiation of DNA synthesis. (
  • It is normally activated by cyclin C and is required for transcription elongation of the serum response genes (immediate early genes [IEGs]) FOS, EGR1, and cJUN. (
  • RV-cyclin does not control CDK8 specificity but instead enhances CDK8's effects on regulated genes, an important distinction for its use to delineate natural CDK8 targets. (
  • also named PITSLRE) is part of the large family of p34 cdc2 -related kinases whose functions appear to be linked with cell cycle progression, tumorigenesis, and apoptotic signaling. (
  • However, the current limitation in structural diversity of kinase inhibitors has complicated efforts to identify effective treatments of diseases that involve protein kinase signaling pathways. (
  • The discovery of this new class of ATP-site-directed protein kinase inhibitors, aminoimidazo[1,2- a ]pyridines, provides the basis for a new medicinal chemistry tool to be used in the search for effective treatments of cancer and other diseases that involve protein kinase signaling pathways. (
  • Recently, some members of the proteolysis pathways involved in the control of cyclin E and KIP1 protein levels have been found to be altered in certain types of cancer. (
  • Unexpectedly, MIP-HSD1 tg/+ mice exhibited a reversal of high fat-induced β-cell failure through augmentation of the number and intrinsic function of small islets in association with induction of heat shock, protein kinase A, and extracellular signal-related kinase and p21 signaling pathways. (
  • This phase I, open-label, first-in-human study determined dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of PD 0332991, an oral cyclin-dependent kinase 4/6 inhibitor with potent anti-proliferative activity in vitro/vivo. (
  • Pan class I phosphatidylinositol-3-kinase (PI3K) inhibitor with predominant inhibitory activity against PI3K-alpha and PI3K-delta isoforms expressed in malignant B cells. (
  • 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 . (
  • Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (
  • Effects of phosphorylation of threonine 160 on cyclin-dependent kinase 2 structure and activity. (
  • Deregulation of PP2A enzymes also affects the activity of many Ser/Thr protein kinases implicated in AD. (
  • Avraham E, Rott R, Liani E, Szargel R, Engelender S. Phosphorylation of Parkin by the cyclin-dependent kinase 5 at the linker region modulates its ubiquitin-ligase activity and aggregation. (
  • Because flavin mononucleotide and flavin adenine dinucleotide act as electron carriers for a range of redox reactions, including the oxidative metabolism of macronutrients and electron transport chains (2), riboflavin deficiency leads to reduced activity of flavin-dependent enzymes, such as glutathione reductase (3), flavin adenine dinucleotide-dependent endoplasmic reticulum oxidoreductin 1 (4), and sulfhydryl oxidases (5). (
  • TUNEL positive nuclei and caspase-3 activity were augmented by 92% and 36%, respectively, following injury in the CRb(L/L) mice demonstrating that loss of Rb in the heart significantly exacerbates I/R injury. (
  • Upon external signals, CDK inhibitors can be used to block the CDK kinase activity, thereby preventing the cell cycle from being driven forward. (
  • Structure-Activity Relationships for a Novel Series of Pyrido[2,3-d]pyrimidine Tyrosine Kinase Inhibitors," Journal of Medicinal Chemistry, Mar. 6, 1997, pp. 2296-2303, vol. 40. (
  • Structure-Activity Relationships Against Selected Tyrosine Kinases and In Vitro and In Vivo Anticancer Activity," Journal of Medicinal Chemistry, Apr. (
  • The RAF/mitogen-activated protein kinase, extracellular signal-regulated kinase kinase (MEK)/ERK signaling cascade regulates multiple processes required for the proliferation and survival of normal cells. (
  • Cyclin-dependent kinase 5 regulates PSD-95 ubiquitination in neurons. (
  • Flavopiridol has been tested at various dosing levels and schedules in both hematologic ( 7, 8 ) and solid tumor malignancies ( 3 , 9 , 10 ). (
  • Currently, the most widely used treatment guidelines, St. Gallen [ 3 ] and the US National Institutes of Health (NIH) [ 2 ] consensus criteria, assess a patient's risk of distant metastases based on clinical prognostic factors such as tumor size, lymph node status, and histologic grade. (
  • A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. (
  • Screening for inhibitors of some of these kinases has already yielded some potent and selective compounds with promising potential for the treatment of human diseases. (
  • A potent and selective inhibitor of cyclin-dependent kinases. (
  • Discovery of a Patent and Selective Inhibitor of Cyclin-Dependent Kinase 4/6," Journal of Medicinal Chemistry, Aug. 6, 2004, pp. 2388-2406, vol. 28. (
  • Conversely, the structures of the inactive states of kinase-family members can vary widely from each other, a principle that can be exploited to improve the specificity of kinase inhibitors. (
  • Signalling specificity of Ser/Thr protein kinases through docking-site-mediated interactions. (
  • The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases. (
  • These are compounds containing an indole moiety, which consists of pyrrolidine ring fused to benzene to form 2,3-dihydroindole. (
  • These compounds included a myristic acid analog known to interact with Src family kinases and an inhibitor of cyclin dependent kinase 2, demonstrating that high-throughput chemical screens combined with high-resolution behavioral assays provide a powerful approach for the discovery of novel cognitive modulators. (
  • Fig. 3: AURKA suppression enhances sensitivity and drives cell death in response to PI3K-pathway inhibitors in breast cancer cell lines. (
  • The frequency of these alterations alone clearly implies that abrogation of the G 1 checkpoint or acceleration of the Cdk4/cyclin D pathway provides a distinct advantage to cancer cells in terms of proliferation and perhaps survival. (
  • A significant aspect of this reprogramming involves changes in the glycolytic pathway, referred to as the Warburg effect [ 3 , 4 ]. (
  • This book contains both review and synthesis of new pyrazolo[3,4-d]pyrimidine derivatives as cycline dependent kinase inhibitors (CDKIs). (
  • Protein kinases may be characterized by their regulation mechanisms. (
  • Figure 3: CDK regulation and opportunities for therapeutic intervention. (
  • Regulation of the cyclin D3 promoter by E2F1. (
  • 100 µg, ABP-PAB-21028]] Considerable evidence suggests that Polo-Like Kinase (PLK) plays an important role in cll cycle regulation. (
  • Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2. (
  • Anti-CDK12 antibodies revealed CDK12 in these immunoprecipitations in the absence (lanes 3 and 6) or presence (lanes 4 and 7) of RNase A by Western blotting (upper panels). (
  • Your search returned 2 cyclin-dependent kinase 16 S homeolog Antibodies across 2 suppliers. (
  • The second contains cyclins T1, T2 or K and Cdk9, which are required for the elongation of transcription. (
  • The proliferation of eukaryotic cells typically involves an orderly progression through four distinct phases of the cell cycle: G 1 , S, G 2 , and M ( 1 -3 ). (
  • In Vitro Pharmacological Characterization of PD 166285, a New Nanomolar Potent and Broadly Active Protein Tyrosine Kinase Inhibitor," Journal of Pharmacology and Experimental Therapeutics, Aug. 4, 1997, 1423-1444, vol. 283, No. 3.cited by other. (
  • Protein kinases constitute a large family of structurally related enzymes that are responsible for the control of a wide variety of signal transduction processes within the cell (Hardie, G. and Hanks, S. (1995) The Protein Kinase Facts Book. (
  • Amember of STAT is a latent cytoplasmic transcription factor that mediates cytokine signal transduction ( 1 , 2 , 3 , 4 ). (