Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.
A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.
A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.
A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.
Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.
A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.
A cyclin subtype that binds to the CYCLIN-DEPENDENT KINASE 3 and CYCLIN-DEPENDENT KINASE 8. Cyclin C plays a dual role as a transcriptional regulator and a G1 phase CELL CYCLE regulator.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
A cyclin subtype that is specific for CYCLIN-DEPENDENT KINASE 4 and CYCLIN-DEPENDENT KINASE 6. Unlike most cyclins, cyclin D expression is not cyclical, but rather it is expressed in response to proliferative signals. Cyclin D may therefore play a role in cellular responses to mitogenic signals.
The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.
A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.
A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION.
A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.
A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.
A potent inhibitor of CYCLIN-DEPENDENT KINASES in G1 PHASE and S PHASE. In humans, aberrant expression of p57 is associated with various NEOPLASMS as well as with BECKWITH-WIEDEMANN SYNDROME.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
Agents that inhibit PROTEIN KINASES.
A cyclin D subtype which is regulated by GATA4 TRANSCRIPTION FACTOR. Experiments using KNOCKOUT MICE suggest a role for cyclin D2 in granulosa cell proliferation and gonadal development.
A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.
A cell line derived from cultured tumor cells.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
A cyclin G subtype that is constitutively expressed throughout the cell cycle. Cyclin G1 is considered a major transcriptional target of TUMOR SUPPRESSOR PROTEIN P53 and is highly induced in response to DNA damage.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
A transcription factor that possesses DNA-binding and E2F-binding domains but lacks a transcriptional activation domain. It is a binding partner for E2F TRANSCRIPTION FACTORS and enhances the DNA binding and transactivation function of the DP-E2F complex.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Established cell cultures that have the potential to propagate indefinitely.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Transport proteins that carry specific substances in the blood or across cell membranes.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
A cyclin B subtype that colocalizes with GOLGI APPARATUS during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 9. Unlike traditional cyclins, which regulate the CELL CYCLE, type T cyclins appear to regulate transcription and are components of positive transcriptional elongation factor B.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
A cyclin subtype that is found as a component of a heterotrimeric complex containing cyclin-dependent kinase 7 and CDK-activating kinase assembly factor. The complex plays a role in cellular proliferation by phosphorylating several CYCLIN DEPENDENT KINASES at specific regulatory threonine sites.
An unusual cyclin subtype that is found highly expressed in terminally differentiated cells. Unlike conventional cyclins increased expression of cyclin G2 is believed to cause a withdrawal of cells from the CELL CYCLE.
The rate dynamics in chemical or physical systems.
A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Elements of limited time intervals, contributing to particular results or situations.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
A group of phenyl benzopyrans named for having structures like FLAVONES.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
An E2F transcription factor that represses GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F4 recruits chromatin remodeling factors indirectly to target gene PROMOTER REGIONS through RETINOBLASTOMA LIKE PROTEIN P130 and RETINOBLASTOMA LIKE PROTEIN P107.
Proteins prepared by recombinant DNA technology.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
The process by which a DNA molecule is duplicated.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Cell regulatory signaling system that controls progression through S PHASE and stabilizes the replication forks during conditions that could affect the fidelity of DNA REPLICATION, such as DNA DAMAGE or depletion of nucleotide pools.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
A cyclin subtype that is found abundantly in post-mitotic tissues. In contrast to the classical cyclins, its level does not fluctuate during the cell cycle.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
The relationship between the dose of an administered drug and the response of the organism to the drug.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
A ubiquitously expressed regulatory protein that contains a retinoblastoma protein binding domain and an AT-rich interactive domain. The protein may play a role in recruiting HISTONE DEACETYLASES to the site of RETINOBLASTOMA PROTEIN-containing transcriptional repressor complexes.
A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
The B-cell leukemia/lymphoma-1 genes, associated with various neoplasms when overexpressed. Overexpression results from the t(11;14) translocation, which is characteristic of mantle zone-derived B-cell lymphomas. The human c-bcl-1 gene is located at 11q13 on the long arm of chromosome 11.
Tumors or cancer of the human BREAST.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Tumor suppressor genes located on human chromosome 9 in the region 9p21. This gene is either deleted or mutated in a wide range of malignancies. (From Segen, Current Med Talk, 1995) Two alternatively spliced gene products are encoded by p16: CYCLIN-DEPENDENT KINASE INHIBITOR P16 and TUMOR SUPPRESSOR PROTEIN P14ARF.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3.
A casein kinase that was originally described as a monomeric enzyme with a molecular weight of 30-40 kDa. Several ISOENZYMES of casein kinase I have been found which are encoded by separate genes. Many of the casein kinase I isoenzymes have been shown to play distinctive roles in intracellular SIGNAL TRANSDUCTION.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.
A protein kinase encoded by the Saccharomyces cerevisiae CDC28 gene and required for progression from the G1 PHASE to the S PHASE in the CELL CYCLE.

Induced expression of p16(INK4a) inhibits both CDK4- and CDK2-associated kinase activity by reassortment of cyclin-CDK-inhibitor complexes. (1/1711)

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

Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (2/1711)

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

Progesterone inhibits estrogen-induced cyclin D1 and cdk4 nuclear translocation, cyclin E- and cyclin A-cdk2 kinase activation, and cell proliferation in uterine epithelial cells in mice. (3/1711)

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

Functions of cyclin A1 in the cell cycle and its interactions with transcription factor E2F-1 and the Rb family of proteins. (4/1711)

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

Heparin inhibits proliferation of myometrial and leiomyomal smooth muscle cells through the induction of alpha-smooth muscle actin, calponin h1 and p27. (5/1711)

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

Impact of 9-(2-phosphonylmethoxyethyl)adenine on (deoxy)ribonucleotide metabolism and nucleic acid synthesis in tumor cells. (6/1711)

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

A new pathway for mitogen-dependent cdk2 regulation uncovered in p27(Kip1)-deficient cells. (7/1711)

BACKGROUND: The ability of cyclin-dependent kinases (CDKs) to promote cell proliferation is opposed by cyclin-dependent kinase inhibitors (CKIs), proteins that bind tightly to cyclin-CDK complexes and block the phosphorylation of exogenous substrates. Mice with targeted CKI gene deletions have only subtle proliferative abnormalities, however, and cells prepared from these mice seem remarkably normal when grown in vitro. One explanation may be the operation of compensatory pathways that control CDK activity and cell proliferation when normal pathways are inactivated. We have used mice lacking the CKIs p21(Cip1) and p27(Kip1) to investigate this issue, specifically with respect to CDK regulation by mitogens. RESULTS: We show that p27 is the major inhibitor of Cdk2 activity in mitogen-starved wild-type murine embryonic fibroblasts (MEFs). Nevertheless, inactivation of the cyclin E-Cdk2 complex in response to mitogen starvation occurs normally in MEFs that have a homozygous deletion of the p27 gene. Moreover, CDK regulation by mitogens is also not affected by the absence of both p27 and p21. A titratable Cdk2 inhibitor compensates for the absence of both CKIs, and we identify this inhibitor as p130, a protein related to the retinoblastoma gene product Rb. Thus, cyclin E-Cdk2 kinase activity cannot be inhibited by mitogen starvation of MEFs that lack both p27 and p130. In addition, cell types that naturally express low amounts of p130, such as T lymphocytes, are completely dependent on p27 for regulation of the cyclin E-Cdk2 complex by mitogens. CONCLUSIONS: Inhibition of Cdk2 activity in mitogen-starved fibroblasts is usually performed by the CKI p27, and to a minor extent by p21. Remarkably p130, a protein in the Rb family that is not related to either p21 or p27, will directly substitute for the CKIs and restore normal CDK regulation by mitogens in cells lacking both p27 and p21. This compensatory pathway may be important in settings in which CKIs are not expressed at standard levels, as is the case in many human tumors.  (+info)

Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27(Kip1). (8/1711)

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

Recombinant human CDKN1B protein, fused to His-tag at N-terminus, was expressed in E. coli and purified by using conventional chromatography. MW: 24.2 kDa.
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The cyclin-dependent kinase (CDK) inhibitor p27Kip1 has been shown to regulate cellular proliferation via inhibition of CDK activities. routine and g27Kip1 (hereafter g27) can regulate CDK actions.1-3 The p27 protein was originally known as an inhibitor of CDK activities for things containing CDK2 and shown to inhibit cyclin E and cyclin A activities which regulate G1 and S phase traverse.4-6 In addition to CDK inhibition, g27 provides other multifarious connections with cyclin N/cdk4 processes putatively.7 Since cellular amounts of g27 are elevated in response to high cell thickness, serum deprival, and TGF, it was hypothesized g27 brought cells into quiescence and held them in G0 through the inhibition of CDK actions.8 Numerous reviews have got characterized the control of p27 including the control of its transcription,9,10 translation,11,12 post-translational adjustments.7,13,14 cellular localization15-19 and balance.20-23 The regulations of its stability has a main role in adjusting mobile ...
TY - JOUR. T1 - Systematic determination of human cyclin dependent kinase (CDK)-9 interactome identifies novel functions in RNA splicing mediated by the DEAD Box (DDX)-5/17 RNA helicases. AU - Yang, Jun. AU - Zhao, Yingxin. AU - Kalita, Mridul. AU - Li, Xueling. AU - Jamaluddin, Mohammad. AU - Tian, Bing. AU - Edeh, Chukwudi B.. AU - Wiktorowicz, John E.. AU - Kudlicki, Andrzej. AU - Brasier, Allan R.. PY - 2015/10/1. Y1 - 2015/10/1. N2 - Inducible transcriptional elongation is a rapid, stereotypic mechanism for activating immediate early immune defense genes by the epithelium in response to viral pathogens. Here, the recruitment of a multifunctional complex containing the cyclin dependent kinase 9 (CDK9) triggers the process of transcriptional elongation activating resting RNA polymerase engaged with innate immune response (IIR) genes. To identify additional functional activity of the CDK9 complex, we conducted immunoprecipitation (IP) enrichment-stable isotope labeling LC-MS/MS of the CDK9 ...
Cyclin-dependent kinases (CDKs) are protein kinases characterized by needing a separate subunit - a cyclin - that provides domains essential for enzymatic activity. CDKs play important roles in the control of cell division and modulate transcription in response to several extra- and intracellular cues. The evolutionary expansion of the CDK family in mammals led to the division of CDKs into three cell-cycle-related subfamilies (Cdk1, Cdk4 and Cdk5) and five transcriptional subfamilies (Cdk7, Cdk8, Cdk9, Cdk11 and Cdk20). Unlike the prototypical Cdc28 kinase of budding yeast, most of these CDKs bind one or a few cyclins, consistent with functional specialization during evolution. This review summarizes how, although CDKs are traditionally separated into cell-cycle or transcriptional CDKs, these activities are frequently combined in many family members. Not surprisingly, deregulation of this family of proteins is a hallmark of several diseases, including cancer, and drug-targeted inhibition of specific
Cyclin E is an important regulator of cell cycle progression. Various studies examined the relationship between cyclin E overexpression with the clinical outcome in patients with breast cancer but yie
p27/Kip1 antibody to detect human cyclin-dependent kinase inhibitor 1. Validated on up to 12 cell lysates for western blotting. Try a trial size today.
Lenti ORF clone of Human cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) (CDKN2A), transcript variant 1, mGFP tagged
CDKN2A - CDKN2A (untagged)-Human cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) (CDKN2A), transcript variant 4 available for purchase from OriGene - Your Gene Company.
Phosphorylation of Sic1, a Cyclin-dependent Kinase (Cdk) Inhibitor, by Cdk Including Pho85 Kinase Is Required for Its Prompt Degradation: In the yeast Saccharom
Recombinant Cyclin-Dependent Kinase 10 (CDK10) Protein (His tag). Species: Cow (Bovine). Source: Yeast. Order product ABIN1616360.
Recombinant Cyclin-Dependent Kinase 10 (CDK10) Protein (His tag). Species: Human. Source: Insect Cells. Order product ABIN3091398.
Purified Recombinant Human CDK5 Protein, Myc/DDK-tagged, C13 and N15-labeled from Creative Biomart. Recombinant Human CDK5 Protein, Myc/DDK-tagged, C13 and N15-labeled can be used for research.
https://astx.com/wp-content/uploads/2019/11/logo_white.png 0 0 webadmin https://astx.com/wp-content/uploads/2019/11/logo_white.png webadmin2010-11-29 12:06:482016-11-29 12:06:57Cho et al. 4-(Pyrazol-4-yl)-pyrimidines as Selective Inhibitors of Cyclin-Dependent Kinase 4/6. Journal of Medicinal Chemistry 53, no. 22 2010: 7938-7957. DOI: 10.1021/jm100571n. ...
Mouse anti Human Cdk6 antibody, clone DCS-83 recognizes the human cyclin dependent kinase 6, also known as Cdk6 or Serine/threonine-protei
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
View mouse Cdk11b Chr4:155624854-155649938 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
1GIH: Crystallographic approach to identification of cyclin-dependent kinase 4 (CDK4)-specific inhibitors by using CDK4 mimic CDK2 protein.
pep:known chromosome:VEGA66:5:146231288:146302874:1 gene:OTTMUSG00000025856 transcript:OTTMUST00000063710 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Cdk8 description:cyclin-dependent kinase 8 ...
AZD5438 is a potent inhibitor of CDK1/2/9 with IC50 of 16 nM/6 nM/20 nM. It is less potent to CDK5/6 and also inhibits GSK3β. Phase 1.Quality confirmed by NMR & HPLC. See customer reviews, validations & product citations.
Looking for online definition of cyclin-dependent kinase 15 in the Medical Dictionary? cyclin-dependent kinase 15 explanation free. What is cyclin-dependent kinase 15? Meaning of cyclin-dependent kinase 15 medical term. What does cyclin-dependent kinase 15 mean?
Cyclin-Dependent Kinase 6: Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.
Cyclin-Dependent Kinase 4: Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.
Cyclin-dependent kinase 4 inhibitor D (CDKN2D) is a specific inhibitor of cyclin-dependent kinases CDK4 and CDK6. CDK4 is a subunit of the protein kinase complex that is important for cell cycle G1 ph...
G1 cyclin-dependent kinase (Cdk)-triggered degradation of the S-phase Cdk inhibitor Sic1p has been implicated in the transition from G1 to S phase in the cell cycle of budding yeast. A multidimensional electrospray mass spectrometry technique was used to map G1 Cdk phosphorylation sites in Sic1p both in vitro and in vivo. A Sic1p mutant lacking three Cdk phosphorylation sites did not serve as a substrate for Cdc34p-dependent ubiquitination in vitro, was stable in vivo, and blocked DNA replication. Moreover, purified phosphoSic1p was ubiquitinated in cyclin-depleted G1 extract, indicating that a primary function of G1 cyclins is to tag Sic1p for destruction. These data suggest a molecular model of how phosphorylation and proteolysis cooperate to bring about the G1/S transition in budding yeast. ...
Coxon CR, Anscombe E, Harnor SJ, Martin MP, Carbain B, Golding BT, Hardcastle IR, Harlow LK, Korolchuk S, Matheson CJ, Newell DR, Noble ME, Sivaprakasam M, Tudhope SJ, Turner DM, Wang LZ, Wedge SR, Wong C, Griffin RJ, Endicott JA, Cano C. Cyclin-Dependent Kinase (CDK) Inhibitors: Structure-Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines. J Med Chem. 2017 03 09; 60(5):1746-1767 ...
Substituted guanines and pyrimidines were tested as inhibitors of cyclin B1/CDK1 and cyclin A3/CDK2 and soaked into crystals of monomeric CDK2. O6-Cyclohexylmethylguanine (NU2058) was a competitive inhibitor of CDK1 and CDK2 with respect to ATP (Ki values: CDK1, 5 +/- 1 microM; CDK2, 12 +/- 3 microM) and formed a triplet of hydrogen bonds (i.e., NH-9 to Glu 81, N-3 to Leu 83, and 2-NH2 to Leu 83). The triplet of hydrogen bonding and CDK inhibition was reproduced by 2,6-diamino-4-cyclohexylmethyloxy-5-nitrosopyrimidine (NU6027, Ki values: CDK1, 2.5 +/- 0.4 microM; CDK2, 1.3 +/- 0.2 microM). Against human tumor cells, NU2058 and NU6027 were growth inhibitory in vitro (mean GI50 values of 13 +/- 7 microM and 10 +/- 6 microM, respectively), with a pattern of sensitivity distinct from flavopiridol and olomoucine. These CDK inhibition and chemosensitivity data indicate that the distinct mode of binding of NU2058 and NU6027 has direct consequences for enzyme and cell growth inhibition.
Dive into the research topics of An analysis of available biomarker data for targeting cyclin-dependent kinases 4 and 6 (CDK4/6) in breast cancer. Together they form a unique fingerprint. ...
The conversation the turned to patient eligibility and the panel agreed that it was prudent to offer the best possible treatment first to patients, where possible, due to the proven response rates seen with CDK 4/6 inhibitors. This point was of particular interest to Dr Beresford as ribociclib and palbocilcib are not approved for 2nd line use in the U.K., and therefore will not be an option for those who are treated with hormone therapy, for example, as an initial option. The panel also reiterated the importance of considering CDK 4/6 inhibitors as a 1st line option to avoid the over use of chemotherapy; a strategy that was backed up by the PALOMA-1 study that showed treatment with a CDK 4/6 inhibitor delayed the time until a patient received subsequent chemotherapy treatment ...
Unicellular organisms such as yeasts require a single cyclin-dependent kinase, Cdk1, to drive cell division. In contrast, mammalian cells are thought to require the sequential activation of at least four different cyclin-dependent kinases, Cdk2, Cdk3, Cdk4 and Cdk6, to drive cells through interphase …
Professor Nadia Harbeck Chairs an expert discussion on the latest in CDK inhibition in breast cancer and what this means for patients for ecancer at the 40th
Cyclin-dependent kinases (CDKs) contribute to the cancer hallmarks of uncontrolled proliferation and increased survival. As a result, over the last two decades substantial efforts have been directed towards identification and development of pharmaceutical CDK inhibitors. Insights into the biological consequences of CDK inhibition in specific tumor types have led to the successful development of CDK4/6 inhibitors as treatments for certain types of breast cancer. More recently, a new generation of pharmaceutical inhibitors of CDK enzymes that regulate the transcription of key oncogenic and pro-survival proteins, including CDK9, have entered clinical development. Here, we provide the first disclosure of the chemical structure of fadraciclib (CYC065), a CDK inhibitor and clinical candidate designed by further optimization from the aminopurine scaffold of seliciclib. We describe its synthesis and mechanistic characterization. Fadraciclib exhibits improved potency and selectivity for CDK2 and CDK9 ...
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P 276 is a flavone that selectively inhibits the cyclin-dependent kinases Cdk4-D1, Cdk9-T and Cdk1-B, thus inhibiting the pathways necessary for cancer cell
The CDK10/PISSLRE gene has been shown to encode two different CDK-like putative kinases. The function(s) of the gene products are unknown, although a role at the G2/M transition has been suggested. We characterised two novel cDNAs. CDK10 mRNA quantity was not found to be correlated with cell prolife …
NU2058 (O6-(Cyclohexylmethyl)guanine) is a potent, competitive and guanine-based CDK inhibitor with IC50s of 17 μM and 26 μM for CDK2 and CDK1. NU2058 has anti-cancer activity. - Mechanism of Action & Protocol.
1PXK: Discovery of a novel family of CDK inhibitors with the program LIDAEUS: structural basis for ligand-induced disordering of the activation loop
A stable environment minimizes evapora- tive heat loss. 10. Cyclin-dependent kinases participate recomendaad death of neurons evoked by DNA- damaging agents. Daleiden, A.
Your Search Returned No Results.. Sorry. There is currently no product that acts on isoform together.. Please try each isoform separately.. ...
The human cyclin-dependent kinase inhibitor 2A (CDKN2A) gene generates several transcript variants that differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported. One of these, cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) or p16INK4a, interacts with, and sequesters, the E3 ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. Thus, p16-INK4a functions as a tumor suppressor in a variety of cells. Mutations in the CDKN2A gene are often found in many tumors. p16INK4a is also suggested to play a role in controlling cell proliferation and apoptosis during mammary gland development. p16-INK4a is also known as cyclin-dependent kinase 4 inhibitor A, CDK4 inhibitor p16-INK4, cell cycle negative regulator beta, multiple tumor suppressor 1 (MTS-1), ARF, MLM, p14, p16, p19, CMM2, INK4, INK4A, TP16, CDK4I, CDKN2, p14-ARF, p19-ARF, and p16-INK4.. ...
TY - JOUR. T1 - Molecular cloning of a cyclin-like protein associated with cyclin-dependent kinase 3 (cdk 3) in vivo. AU - Matsuoka, Masaaki. AU - Matsuura, Yoshiharu. AU - Semba, Kentaro. AU - Nishimoto, Ikuo. PY - 2000/7/5. Y1 - 2000/7/5. N2 - 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. p70(ik3-1) (a 70-kDa protein designated as p70(ik3-1)) seems to belong to the cyclin family as its C-terminal domain composed of 124 amino acids resembles the highly conserved cyclin box. Coimmunoprecipitation indicated that p70(ik3-1) binds to p35(cdk3) in vivo. The ik3-1 gene may belong to a multigene family and is highly conserved during evolution. mRNA expression of ik3-1 was low in the early ...
Cyclin-dependent kinases (CDKs) are a family of sugar kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They are present in all known eukaryotes, and their regulatory function in the cell cycle has been evolutionarily conserved. In fact, yeast cells can proliferate normally when their CDK gene has been replaced with the homologous human gene. CDKs are relatively small proteins, with molecular weights ranging from 34 to 40 kDa, and contain little more than the kinase domain. By definition, a CDK binds a regulatory protein called a cyclin. Without cyclin, CDK has little kinase activity; only the cyclin-CDK complex is an active kinase. CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases. The consensus sequence for the phosphorylation site in the amino acid sequence of a CDK substrate is [S/T*]PX[K/R], where S/T* is the ...
Vol 7: PD-0332991 induces G1 arrest of colorectal carcinoma cells through inhibition of the cyclin-dependent kinase-6 and retinoblastoma protein axis.. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
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Complete information for CDK10 gene (Protein Coding), Cyclin Dependent Kinase 10, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for CDK19 gene (Protein Coding), Cyclin Dependent Kinase 19, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
The researchers examined a protein called cyclin-dependent kinase 2 (CDK2), which works as a quality control inspector. As normal cells divide, they pause in the replication process when they find inaccurate genetic code embedded in their DNA. The health and well-being of offspring cells depends on accurate genetic code transfer from one generation of cells to the next. The Mayo researchers showed that when errors in genes are irreparable, CDK2 modifies another cellular protein -- FOXO1 -- to send a signal that results in the death of the cell. This protein-to-protein relationship invites targeted drug intervention to control unregulated growth of cancer cells ...
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Proliferation depends on progression through four distinct phases of the cell cycle G0/G1, S, G2 and M which is regulated by several cyclin-dependent kinases (CDKs ...
CDK8 antibody (cyclin-dependent kinase 8) for ICC/IF, IP, WB. Anti-CDK8 pAb (GTX22955) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
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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 ...
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. ( ...
"CDK2 cyclin dependent kinase 2 [Homo sapiens (human)]". Gene - NCBI. Retrieved 1 December 2019. Hinchcliffe EH, Li C, Thompson ... This link between the cell cycle and the centrosome cycle is mediated by cyclin-dependent kinase 2 (Cdk2). Cdk2 is a protein ... Matsumoto Y, Hayashi K, Nishida E (April 1999). "Cyclin-dependent kinase 2 (Cdk2) is required for centrosome duplication in ... Lacey KR, Jackson PK, Stearns T (March 1999). "Cyclin-dependent kinase control of centrosome duplication". Proceedings of the ...
... cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II ... cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II ... Cyclin-dependent kinase 5 activator 2 is an enzyme that in humans is encoded by the CDK5R2 gene. The protein encoded by this ... "Entrez Gene: CDK5R2 cyclin-dependent kinase 5, regulatory subunit 2 (p39)". Dhavan R, Greer PL, Morabito MA, Orlando LR, Tsai ...
Cyclin-dependent kinase-like 2 is an enzyme that in humans is encoded by the CDKL2 gene. This gene product is a member of a ... "Entrez Gene: CDKL2 cyclin-dependent kinase-like 2 (CDC2-related kinase)". Human CDKL2 genome location and CDKL2 gene details ... Overview of all the structural information available in the PDB for UniProt: Q92772 (Cyclin-dependent kinase-like 2) at the ... 2005). "Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene are associated with severe ...
Cyclin-dependent kinase 2-associated protein 1 is an enzyme that in humans is encoded by the CDK2AP1 gene. The protein encoded ... CDK2AP1 has been shown to interact with Cyclin-dependent kinase 2. It interacts with unnamed protein product (BC006130) which ... "p12DOC-1 Is a Novel Cyclin-Dependent Kinase 2-Associated Protein". Mol. Cell. Biol. 20 (17): 6300-7. doi:10.1128/MCB.20.17.6300 ... "p12DOC-1 Is a Novel Cyclin-Dependent Kinase 2-Associated Protein". Mol. Cell. Biol. 20 (17): 6300-7. doi:10.1128/MCB.20.17.6300 ...
p16Ink4a also activates pRB, but through inactivation of cyclin-dependent kinase 4 (Cdk 4) and cyclin-dependent kinase 6 (Cdk 6 ... The p16 protein is a cyclin dependent kinase inhibitor (CDK) inhibitor and it activates Rb tumor suppressor. p16 binds to CDK 4 ... p53 activates p21 which deactivates cyclin-dependent kinase 2(Cdk 2). Without Cdk 2, retinoblastoma protein (pRB) remains in ... The prolonged DDR activates both ATM and ATR DNA damage kinases. The phosphorylation cascade initiated by these two kinases ...
It was identified as a cyclin-dependent kinase inhibitor, and has been shown to interact with, and dephosphorylate CDK2 kinase ... 2005). "Binding of HTm4 to cyclin-dependent kinase (Cdk)-associated phosphatase (KAP).Cdk2.cyclin A complex enhances the ... "Dephosphorylation of Cdk2 Thr160 by the cyclin-dependent kinase-interacting phosphatase KAP in the absence of cyclin". Science ... Cyclin-dependent kinase inhibitor 3 is an enzyme that in humans is encoded by the CDKN3 gene. The protein encoded by this gene ...
March 2015). "Phosphorylation of hnRNP K by cyclin-dependent kinase 2 controls cytosolic accumulation of TDP-43". Human ... "Stress granules regulate double-stranded RNA-dependent protein kinase activation through a complex containing G3BP1 and Caprin1 ... Wasserman T, Katsenelson K, Daniliuc S, Hasin T, Choder M, Aronheim A (January 2010). "A novel c-Jun N-terminal kinase (JNK)- ... Reineke LC, Tsai WC, Jain A, Kaelber JT, Jung SY, Lloyd RE (February 2017). "Casein Kinase 2 Is Linked to Stress Granule ...
... 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». ...
... cyclins and cyclin dependent kinases". Oncogene. 15 (2): 143-57. doi:10.1038/sj.onc.1201252. PMID 9244350. Chen Y, Farmer AA, ... "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 ...
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 ...
For instance, Cdk1 (Cyclin-dependent kinase 1) activates condensin I, whereas CK2 (Casein kinase 2) negatively regulate its ... PMID 26904946.CS1 maint: multiple names: authors list (link) Kimura K, Hirano T (1997). "ATP-dependent positive supercoiling of ... Condensin subunits are subjected to various posttranslational modifications in a cell cycle-dependent manner. Among them, the ... Mascarenhas J, Soppa J, Strunnikov AV, Graumann PL (2002). "Cell cycle-dependent localization of two novel prokaryotic ...
This phosphatase has been shown to dephosphorylate cyclin-dependent kinases (CDKs), and thus may be involved in cell cycle ... Cheng A, Ross KE, Kaldis P, Solomon MJ (2000). "Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases ... Cheng A, Kaldis P, Solomon MJ (2000). "Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type 2C alpha ... "Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type 2C alpha and beta 2 isoforms". J. Biol. Chem. ...
Cheng A, Kaldis P, Solomon MJ (Nov 2000). "Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type 2C ... Cyclin-dependent kinase 2, Cyclin-dependent kinase 6, FAM40A, IGBP1, MOBKL3, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R3B, PPP2R5A, ... "Phosphorylation and activation of hamster carbamyl phosphate synthetase II by cAMP-dependent protein kinase. A novel mechanism ... Bennin DA, Don AS, Brake T, McKenzie JL, Rosenbaum H, Ortiz L, DePaoli-Roach AA, Horne MC (Jul 2002). "Cyclin G2 associates ...
... and the cyclin dependent kinase inhibitors P27 and P21". Leuk. Lymphoma. 43 (1): 51-7. doi:10.1080/10428190210195. PMID ... "Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis". Proc. ... "Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation". J. ... 2 and refinement to a 3.2-cM region". Genomics. 66 (1): 119-21. doi:10.1006/geno.2000.6192. PMID 10843814. "Entrez Gene: TGFB1 ...
Cyclin-dependent kinases regulatory subunit 2 is a protein that in humans is encoded by the CKS2 gene. CKS2 protein binds to ... 2007). "Gene expression of cyclin-dependent kinase subunit Cks2 is repressed by the tumor suppressor p53 but not by the related ... the catalytic subunit of the cyclin dependent kinases and is essential for their biological function. The CKS2 mRNA is found to ... "Entrez Gene: CKS2 CDC28 protein kinase regulatory subunit 2". Human CKS2 genome location and CKS2 gene details page in the UCSC ...
... a cyclin-dependent kinase inhibitor, is dependent on p53 signaling". PLOS ONE. 8 (3): e59588. doi:10.1371/journal.pone.0059588 ... Fu W, Ma L, Chu B, Wang X, Bui MM, Gemmer J, Altiok S, Pledger WJ (Jun 2011). "The cyclin-dependent kinase inhibitor SCH 727965 ... Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. Dinaciclib ( ... Apoptosis of osteosarcoma cultures can be induced by the combination of the cyclin-dependent kinase inhibitor SCH727965 and a ...
Cyclin E1, Cyclin-dependent kinase 2, HDAC1, Prohibitin, and RBBP8. Pocket protein family GRCh38: Ensembl release 89: ... Yang R, Müller C, Huynh V, Fung YK, Yee AS, Koeffler HP (Mar 1999). "Functions of cyclin A1 in the cell cycle and its ... Shanahan F, Seghezzi W, Parry D, Mahony D, Lees E (Feb 1999). "Cyclin E associates with BAF155 and BRG1, components of the ... Lacy S, Whyte P (May 1997). "Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 ...
He also published many papers on the structures of protein molecules including human Ras, human cyclin dependent kinase 2 and ...
... loss of m6A also results in the down regulation of tumor suppressors like cyclin-dependent kinase inhibitor 2A (CDKN2A) and ... This can be seen in the delay in the tRNA accommodation, which is dependent upon both the position of the m6A in the mRNA ... In addition, expression of the ncRNAs needed to guide RNA-dependent PUS enzymes also goes up in response to fear. There are ... Leighton LJ, Ke K, Zajaczkowski EL, Edmunds J, Spitale RC, Bredy TW (March 2018). "Experience-dependent neural plasticity, ...
... has been shown to interact with: AKT1, CKS1B, Cyclin D3, Cyclin E1, Cyclin-dependent kinase 2, Cyclin-dependent kinase 4 ... "Assembly of cyclin D-dependent kinase and titration of p27Kip1 regulated by mitogen-activated protein kinase kinase (MEK1)". ... "Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas". ... Cyclin-dependent kinase inhibitor 1B (p27Kip1) is an enzyme inhibitor that in humans is encoded by the CDKN1B gene. It encodes ...
A number of additional proteins also interact with MAPK15, including cyclin-dependent kinase 2 (CDK2), mitogen-activated ... MAP kinases are also known as extracellular signal-regulated kinases (ERKs), and are involved in signaling cascades that ... Mitogen-activated protein kinase 15, also known as MAPK15, ERK7, or ERK8, is an enzyme that in humans is encoded by the MAPK15 ... It contains two SH3 (SRC homology 3) binding motifs in its C-terminal region, and is likely activated by an SRC-dependent ...
The encoded protein is phosphorylated by cyclin A/cyclin-dependent kinase 2 during the S-phase of the cell cycle and possesses ... MYBL2 has been shown to interact with: CDK9 CREB-binding protein Cyclin A1 Cyclin-dependent kinase inhibitor 1C EP300 PARP1 ... Joaquin M, Watson RJ (November 2003). "The cell cycle-regulated B-Myb transcription factor overcomes cyclin-dependent kinase ... April 2001). "Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at functionally important serine ...
... dependent phosphorylation of the RNA polymerase C-terminal domain. EBNA2 requires C-promoter binding factor 1 (CBF1) to aid in ... The Epstein-Barr virus nuclear antigen 2 (EBNA-2) is one of the six EBV viral nuclear proteins expressed in latently infected B ... Ling PD, Rawlins DR, Hayward SD (October 1993). "The Epstein-Barr virus immortalizing protein EBNA-2 is targeted to DNA by a ... Wu DY, Kalpana GV, Goff SP, Schubach WH (September 1996). "Epstein-Barr virus nuclear protein 2 (EBNA2) binds to a component of ...
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 ...
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 ...
... has been shown to interact with: BEGAIN, BRCA1, BRF1, Cyclin A2, Cyclin-dependent kinase 2, E2F1 ... "Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4". Molecular and ... Joaquin M, Watson RJ (Nov 2003). "The cell cycle-regulated B-Myb transcription factor overcomes cyclin-dependent kinase ... "Regulation of the retinoblastoma protein-related protein p107 by G1 cyclin-associated kinases". Proceedings of the National ...
... has been shown to directly prevent cell cycle G1 to S phase transition by decreasing levels of cyclin-dependent kinase complex ... In mature muscle, myostatin inhibits Akt, a kinase that is sufficient to cause muscle hypertrophy, in part through the ... Growth of cardiomyocytes may also be hindered by myostatin-regulated inhibition of protein kinase p38 and the serine-threonine ... This process includes mitogen-activated protein kinases and binding of the MEF2 transcription factor within the promoter region ...
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.[ ...
The cell cycle is regulated by a series of signalling factors and complexes such as cyclin-dependent kinases and p53, to name a ... Kaneshiro, Edna (May 2, 2001). Cell Physiology Sourcebook: A Molecular Approach (3rd ed.). Academic Press. ISBN 978-0123877383. ... doi:10.1007/978-94-007-5561-1_2. ISBN 978-94-007-5560-4.. CS1 maint: Extra text: editors list (link) electronic-book ISBN 978- ... Robert Hooke was the first person to term the building block of all living organisms as "cells" after looking at cork.[2] The ...
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 ...
"Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational ... 234 (2): 257-80. doi:10.1006/jmbi.1993.1582. PMID 8230212.. *^ Swanson R, Hoben P, Sumner-Smith M, Uemura H, Watson L, Söll D ( ... It aminoacylates at the 2'-OH of a terminal adenosine nucleotide on tRNA, and it is usually monomeric or dimeric (one or two ... Regardless of where the aminoacyl is initially attached to the nucleotide, the 2'-O-aminoacyl-tRNA will ultimately migrate to ...
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 ... Jest mieszaniną dwóch stereoizomerów: likareolu i koriandrolu[2]. Otrzymuje się go z olejków eterycznych: linalowego, ... 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 ...
"Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation". Nature Neuroscience. 10 ( ... Src kinase enhances NMDA receptor currents.[98]. *Na+, K+ and Ca2+ not only pass through the NMDA receptor channel but also ... "MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term ... Depolarization of the cell dislodges and repels the Mg2+ and Zn2+ ions from the pore, thus allowing a voltage-dependent flow of ...
... endothelin receptor A and cyclin dependent kinase inhibitor. Mutations in interleukin 6 may be protective.[citation needed]. ... ISBN 978-1-888799-97-2.. *^ a b Chalouhi, Nohra; Loh, Brian L; Hasan, David (25 November 2013). "Review of Cerebral Aneurysm ... 243 (2): 500-8. doi:10.1148/radiol.2431060006. PMID 17293572.. *^ Raymond, J; Guilbert, F; Weill, A; Georganos, SA; Juravsky, L ... 30 (2): 470-476. doi:10.1161/01.STR.30.2.470. PMID 9933290.. CS1 maint: Multiple names: authors list (link) ...
"Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms"। Nature (ইংরেজি ভাষায়)। 411 (6841): 1068-1073 ... G1 ফেজ এর শেষের দিকে পরিবেশগত অবস্থা ঠিক থাকলে যেমন G1 এবং G1/S cyclin - Cdk কমপ্লেক্স সক্রিয় হয়, যা জিনের অভিব্যক্তিকে ... "CLB5-Dependent Activation of Late Replication Origins in S. cerevisiae"। Molecular Cell। 2 (2): 173-182। আইএসএসএন 1097-2765 ... "Causes and consequences of replication stress"। Nature Cell Biology (ইংরেজি ভাষায়)। 16 (1): 2-9। আইএসএসএন 1476-4679। ডিওআই: ...
cyclin-dependent protein serine/threonine kinase inhibitor activity. • protein binding. • cyclin-dependent protein kinase ... cyclin-dependent protein kinase holoenzyme complex. • nucleus. • nucleoplasm. • cytosol. • intracellular membrane-bounded ... Cyclin-dependent kinase inhibitor 1A (p21, Cip1). Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human ... regulation of cyclin-dependent protein serine/threonine kinase activity. • G1/S transition of mitotic cell cycle. • G2/M ...
... phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase" ... "Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV transcription by a Tat-dependent mechanism". J. Immunol. 169 ... 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] ...
"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 ... 2 (8): 469-75. doi:10.1038/35019501. PMID 10934466.. *^ Gupta S, Deepti A, Deegan S, Lisbona F, Hetz C, Samali A (July 2010). ... The Hsp70s are an important part of the cell's machinery for protein folding, and help to protect cells from stress.[2][3] ...
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) ... doi: /10.1007/s10565-019-09496-2. PMID 31820165 *^ a b c d e f ... In order to be released, the protein is cleaved by a calcium-dependent calpain protease. ...
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 ...
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 ...
Cyclin-dependent kinases (CDKs) 4 and 6 are enzymes that have been shown to promote cell division and multiplication in both ... Ribociclib, sold under the brand name Kisqali,[1] is an inhibitor of cyclin D1/CDK4 and CDK6, and is used for the treatment of ... Conversely, drugs that induce CYP3A4, such as rifampicin and St John's Wort, can decrease ribociclib concentrations.[2][6] ... 16%). The drug also increases the QT interval and liver enzymes (alanine transaminase, aspartate transaminase).[2][6] ...
... 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 ... 2 and refinement to a 3.2-cM region». Genomics 66 (1): 119-21. PMID 10843814. doi:10.1006/geno.2000.6192. ...
... 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 ... a b c d Reeves, J. D. and Doms, R. W. (2002) Human immunodeficiency virus type 2. J. Gen. Virol. 83, 1253-1265 PMID 12029140 ... Lancet Infect Dis. 2, 461-71 PMID 12150845. *Xiao, H., Neuveut, C., Tiffany, H. L., Benkirane, M., Rich, E. A., Murphy, P. M. ... Sedangkan, HIV-2 merupakan spesies virus hasil evolusi strain SIV yang berbeda (SIVsmm), ditemukan pada Sooty mangabey, monyet ...
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 ( ... 5 (2): 205-47. doi:10.1046/j.1420-9101.1992.5020205.x.. *^ a b c d e f g h i j Lambert, J.David; Nagy, Lisa M (2003). "The MAPK ... 248 (2): 343-355. doi:10.1006/dbio.2002.0741. PMID 12167409.. *^ a b c Boyer, Barbara C.; Jonathan, Q. Henry (1998). " ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein kinases. This protein ... cyclins and cyclin dependent kinases". Oncogene. 15 (2): 143-57. doi:10.1038/sj.onc.1201252. PMID 9244350. Shintani S, Ohyama H ... the process is controlled by different levels of cyclin-dependent kinases (Cdks) and their partner cyclins. Cells utilize ... "Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4". Molecular and ...
Encodes a member of a plant specific family of cyclin dependent kinases. Also Known As: AT2G38620, CYCLIN-DEPEN... ... cyclin-dependent kinase B1;2 [Arabidopsis thaliana] cyclin-dependent kinase B1;2 [Arabidopsis thaliana]. gi,42569741,ref,NP_ ... cyclin-dependent kinase B1;2 [Arabidopsis thaliana]. NCBI Reference Sequence: NP_181396.2 ... CDK-related protein kinases in plants. [Plant Mol Biol. 2000] CDK-related protein kinases in plants.. Joubès J, Chevalier C, ...
Crystal structure of cyclin-dependent kinase 2.. De Bondt HL1, Rosenblatt J, Jancarik J, Jones HD, Morgan DO, Kim SH. ... Cyclin-dependent kinase 2 (CDK2) is a member of a highly conserved family of protein kinases that regulate the eukaryotic cell ... The structure is bi-lobate, like that of the cyclic AMP-dependent protein kinase, but contains a unique helix-loop segment that ... with ATP and protein substrate binding and probably plays a key part in the regulation of all cyclin-dependent kinases. ...
Structure-guided discovery of cyclin-dependent kinase inhibitors.. Fischmann, T.O., Hruza, A., Duca, J.S., Ramanathan, L., ... Crystal Structure of Cyclin-Dependent Kinase 2 with inhibitor. *DOI: 10.2210/pdb2R3P/pdb ... Cell division protein kinase 2. A. 299. Homo sapiens. Mutation(s): 0 Gene Names: CDK2, CDKN2. EC: 2.7.11.22. ... to the backbone of the kinase hinge region. Even though ab initio computations indicated that the imidazopyrazine core would ...
Structure-guided discovery of cyclin-dependent kinase inhibitors.. Fischmann, T.O., Hruza, A., Duca, J.S., Ramanathan, L., ... Crystal Structure of Cyclin-Dependent Kinase 2 with inhibitor. *DOI: 10.2210/pdb2R3J/pdb ... to the backbone of the kinase hinge region. Even though ab initio computations indicated that the imidazopyrazine core would ...
... and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the ... Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of ... NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome ... Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by ...
Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A. Brenda A. Schulman, Derek L. ... An important question in the cell cycle field is how cyclin-dependent kinases (cdks) target their substrates. We have studied ... Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A ... as different substrate preferences are observed for cdk2 bound to cyclin E or cyclin A and for cdc2 bound to cyclin A or cyclin ...
IPR011009 Kinase-like_dom_sf. IPR000719 Prot_kinase_dom. IPR017441 Protein_kinase_ATP_BS. IPR008271 Ser/Thr_kinase_AS. ... IPR011009 Kinase-like_dom_sf. IPR000719 Prot_kinase_dom. IPR017441 Protein_kinase_ATP_BS. IPR008271 Ser/Thr_kinase_AS. ... cyclin-dependent kinase 2Imported. ,p>Information which has been imported from another database using automatic procedures.,/p ... tr,A0A2D0PKQ8,A0A2D0PKQ8_ICTPU cyclin-dependent kinase 2 OS=Ictalurus punctatus OX=7998 GN=cdk2 PE=3 SV=1 ...
Two such proteins, cyclin-dependent kinase-2 (Cdk2) and its downstream target, the retinoblastoma gene … ... Cyclin-dependent kinase 2 signaling regulates myocardial ischemia/reperfusion injury J Mol Cell Cardiol. 2008 Nov;45(5):610-6. ... Two such proteins, cyclin-dependent kinase-2 (Cdk2) and its downstream target, the retinoblastoma gene product (Rb), also play ...
E-type cyclins E1 (CcnE1) and E2 (CcnE2) are regulatory subunits of cyclin-dependent kinase 2 (Cdk2) and thought to control the ... Cyclin E1 and cyclin-dependent kinase 2 are critical for initiation, but not for progression of hepatocellular carcinoma. ... Cyclin E1 and cyclin-dependent kinase 2 are critical for initiation, but not for progression of hepatocellular carcinoma ... Cyclin E1 and cyclin-dependent kinase 2 are critical for initiation, but not for progression of hepatocellular carcinoma ...
Cyclin-dependent kinase 5 (Cdk5) mediates neurotoxic effects by phosphorylating and inhibiting MEF2. How Cdk5-dependent ... Cyclin-dependent kinase 5 prevents neuronal apoptosis by negative regulation of c-Jun N-terminal kinase 3. EMBO J 21: 324-333. ... Calpain-dependent proteolytic cleavage of the p35 cyclin-dependent kinase 5 activator to p25. J Biol Chem 275: 17166-17172. ... Cyclin-Dependent Kinase 5 Mediates Neurotoxin-Induced Degradation of the Transcription Factor Myocyte Enhancer Factor 2. Xiaoli ...
Recombinant Cyclin-Dependent Kinase 2 (CDK2) Protein. Species: Rat (Rattus). Source: Escherichia coli (E. coli). Order product ... Cyclin-Dependent Kinase Inhibitor 2B (p15, Inhibits CDK4) Proteins * Cyclin-Dependent Kinase Inhibitor 2C (p18, Inhibits CDK4) ... Cyclin-Dependent Kinase 8 Proteins * Cyclin-Dependent Kinase 9 Proteins * Cyclin-Dependent Kinase Inhibitor 1A (p21, Cip1) ... Cyclin-Dependent Kinase 4 Proteins * Cyclin-Dependent Kinase 5 Proteins * Cyclin-Dependent Kinase 5, Regulatory Subunit 1 (p35 ...
Cyclin-Dependent Kinase 2 (CDK2) Protein (GST tag). Species: Human. Source: Baculovirus infected Insect Cells. Order product ... Cyclin-Dependent Kinase 2 (CDK2) protein (GST tag) Protein CDK2 Origin: Human Source: Baculovirus infected Insect Cells, Insect ... p33 (CDK2), Cyclin-dependent kinase 2, Cell division protein kinase 2, p33 protein kinase. Purification. Recombinant full- ... Cyclin-Dependent Kinase 2 (CDK2) (AA 1-298) protein (His tag) Protein ...
... were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepared as a homologue of the 3 ... 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, ... 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 ...
Sensitivity of breast cancer cells to erlotinib depends on cyclin-dependent kinase 2 activity. Fumiyuki Yamasaki, Dongwei Zhang ... Collaborative role of E2F transcriptional activity and G1 cyclin dependent kinase activity in the induction of S phase. Proc ... Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated ... Sensitivity of breast cancer cells to erlotinib depends on cyclin-dependent kinase 2 activity ...
Recent genetic studies indicate that mutations of Cdkl family kinases are associated with neurodevelopmental and ... Recent genetic studies indicate that mutations of Cdkl family kinases are associated with neurodevelopmental and ... is a cdc2-related serine/threonine protein kinase that is postnatally expressed in various brain regions, including the ... is a cdc2-related serine/threonine protein kinase that is postnatally expressed in various brain regions, including the ...
... whereas the induction of cyclin E, cyclin A, cyclin-dependent kinase-2, and cyclin-dependent kinase-4 was strongly inhibited, ... and cyclin-dependent kinase-4 as molecular targets.. S Songia, A Mortellaro, S Taverna, C Fornasiero, E A Scheiber, E Erba, F ... and cyclin-dependent kinase-4 as molecular targets.. S Songia, A Mortellaro, S Taverna, C Fornasiero, E A Scheiber, E Erba, F ... and cyclin-dependent kinase-4 as molecular targets.. S Songia, A Mortellaro, S Taverna, C Fornasiero, E A Scheiber, E Erba, F ...
PRESENTS NEW CYCLIN DEPENDENT KINASE 2 (CDK2) FOCUSED LIBRARY grischenko. Member posted 09-08-2009 08:43 AM This library has ... PRESENTS NEW CYCLIN DEPENDENT KINASE 2 (CDK2) FOCUSED LIBRARY profile. , register. , preferences. , faq. , search. ... Evaluation of 3-Carboxy-4(1H)-quinolones as Inhibitors of Human Protein Kinase CK2. Journal of Medicinal Chemistry 2006, 49 (22 ... targeted compound libraries and protein kinase inhibitors, prescreened anticancer compounds, peptide and chromogenic substrates ...
Serine/threonine-protein kinase involved in the control of the cell cycle, essential for meiosis, but dispensable for mitosis. ... Anti-CDK2, Anti-CDKN2, EC=2.7.11.22, Anti-p33 protein kinase, Anti-Cyclin-dependent kinase 2, Anti-Cell division protein kinase ... Product information "Anti-cdk2 (Cyclin-dependent Kinase 2)" Protein function: Serine/threonine-protein kinase involved in the ... and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the ...
... Fumiyuki Yamasaki,1,2,4 Dongwei ... Collaborative role of E2F transcriptional activity and G1 cyclin dependent kinase activity in the induction of S phase. Proc ... Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated ... led us to study the potential relationship between cyclin-dependent kinases (CDK), particularly CDK2 (12, 13) and erlotinib ...
cdk2-cyclin E. cdk2-cyclin A. cdk1-cyclin B1. cdk4-cyclin D1. cdk5-p25. cdk6-cyclin D3. cdk7-cyclin H. cdk9-cyclin T. ... AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor ... AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor ... AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor ...
The retinoblastoma (RB) and cyclin-dependent kinase inhibitor 2/multiple tumor suppressor gene 1 (CDKN2/MTS1) tumor suppressor ... Immunohistochemical Detection of the Cyclin-dependent Kinase Inhibitor 2/Multiple Tumor Suppressor Gene 1 (CDKN2/MTS1) Product ... Immunohistochemical Detection of the Cyclin-dependent Kinase Inhibitor 2/Multiple Tumor Suppressor Gene 1 (CDKN2/MTS1) Product ... Immunohistochemical Detection of the Cyclin-dependent Kinase Inhibitor 2/Multiple Tumor Suppressor Gene 1 (CDKN2/MTS1) Product ...
CDKN2 encodes a Mr 16,000 protein (p16) that plays a key role in cell cycle control by binding to the cyclin-dependent kinase 4 ... Recently, a putative 9p21 tumor suppressor gene, the cyclin dependent kinase inhibitor 2 (CDKN2) or p16 gene, has been shown to ... Loss of Expression of the p16/Cyclin-dependent Kinase Inhibitor 2 Tumor Suppressor Gene in Melanocytic Lesions Correlates with ... Loss of Expression of the p16/Cyclin-dependent Kinase Inhibitor 2 Tumor Suppressor Gene in Melanocytic Lesions Correlates with ...
IV-2. 1-methylpropyl 2-imidazolyl disulfide. DADS. diallyl disulfide. AIV-2. 2-hydroxy-1-methylpropyl 2-imidazolyl disulfide. ... IV-2 did, however, increase Bcl-2 phosphorylation. These data suggest that the thioredoxin inhibitor IV-2, despite its simple ... The small protein thioredoxin has oncogenic properties and controls cell cycle movement through G1, S, and G2/M phases. The ... We now examined the effects of IV-2 on cell cycle progression. In synchronized tsFT210 mouse mammary carcinoma cells, IV-2 ...
Phosphorylation of GATA3 Thr-156 was detected in mouse thymocytes, and cyclin-dependent kinase 2 (CDK2) was identified as a ... Fbw7 Targets GATA3 through Cyclin-Dependent Kinase 2-Dependent Proteolysis and Contributes to Regulation of T-Cell Development ... Fbw7 Targets GATA3 through Cyclin-Dependent Kinase 2-Dependent Proteolysis and Contributes to Regulation of T-Cell Development ... Fbw7 Targets GATA3 through Cyclin-Dependent Kinase 2-Dependent Proteolysis and Contributes to Regulation of T-Cell Development ...
The encoded protein is the catalytic subunit of the cyclin-dependent protein kinase complex, which regulates progression ... This protein associates with and regulated by other subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 ( ... This gene encodes a member of a family of serine/threonine protein kinases that participate in cell cycle regulation. ... Recombinant Human Cyclin-Dependent Kinase 2, GST-tagged. Sf 9 Insect cells. Human. GST. +Inquiry. ...
... p34 Protein Kinase or Cell Division Protein Kinase 1 or Cell Division Control Protein 2 Homolog or CDK1 or EC 2.7.11.22 or EC ... Cyclin Dependent Kinase 1 (p34 Protein Kinase or Cell Division Protein Kinase 1 or Cell Division Control Protein 2 Homolog or ... Cyclin Dependent Kinase 1 (p34 Protein Kinase or Cell Division Protein Kinase 1 or Cell Division Control Protein 2 Homolog or ... Cyclin Dependent Kinase 1 (p34 Protein Kinase or Cell Division Protein Kinase 1 or Cell Division Control Protein 2 Homolog or ...
Global Markets Directs, Cyclin-Dependent Kinase 2 (p33 Protein... ... p33 Protein Kinase or cdc2-Related Protein Kinase or EC 2.7.11.22) - Pipeline Review, H1 2016 report by Global Markets Direct. ... 65 Pages Report] Check for Discount on Cyclin-Dependent Kinase 2 ( ... p33 Protein Kinase or cdc2-Related Protein Kinase or EC 2.7.11.22) *The report reviews Cyclin-Dependent Kinase 2 (p33 Protein ...
Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit... ... Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase 4 or Cell Division Protein ... Kinase 9 or Serine/Threonine Protein Kinase PITALR or CDK9 or EC 2.7.11.22 or EC 2.7.11.23) - Pipeli report by Global Markets ... 92 Pages Report] Check for Discount on Cyclin Dependent Kinase 9 ( ...
  • Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the CDK2 gene. (wikipedia.org)
  • This protein associates with and is regulated by the regulatory subunits of the complex including cyclin E or A. Cyclin E binds G1 phase Cdk2, which is required for the transition from G1 to S phase while binding with Cyclin A is required to progress through the S phase. (wikipedia.org)
  • Cdk2 is capable of binding to many different cyclins, including cyclins A, B, E, and possibly C. Recent studies suggest Cdk2 binds preferentially to cyclins A and E, while Cdk1 prefers cyclins A and B. Cdk2 becomes active when a cyclin protein (either A or E) binds at the active site located between the N and C lobes of the kinase. (wikipedia.org)
  • Due to the location of the active site, partner cyclins interact with both lobes of Cdk2. (wikipedia.org)
  • Cdk2 contains an important alpha helix located in the C lobe of the kinase, called the C-helix or the PSTAIRE-helix. (wikipedia.org)
  • It is important to note that throughout this activation process, cyclins binding to Cdk2 do not undergo any conformational change. (wikipedia.org)
  • Prior to G1 phase, levels of Cdk4 and Cdk6 increase along with cyclin D. This allows for the partial phosphorylation of Rb, and partial activation of E2F at the beginning of G1 phase, which promotes cyclin E synthesis and increased Cdk2 activity. (wikipedia.org)
  • Cyclin-dependent kinase 2 (CDK2) is a member of a highly conserved family of protein kinases that regulate the eukaryotic cell cycle. (nih.gov)
  • Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. (uniprot.org)
  • NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. (uniprot.org)
  • Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. (uniprot.org)
  • We have studied the role of a conserved hydrophobic patch on the surface of cyclin A in substrate recognition by cyclin A-cdk2. (pnas.org)
  • This hydrophobic patch is ≈35Å away from the active site of cdk2 and contains the MRAIL sequence conserved among a number of mammalian cyclins. (pnas.org)
  • In the x-ray structure of cyclin A-cdk2-p27, this hydrophobic patch contacts the RNLFG sequence in p27 that is common to a number of substrates and inhibitors of mammalian cdks. (pnas.org)
  • We find that mutation of this hydrophobic patch on cyclin A eliminates binding to proteins containing RXL motifs without affecting binding to cdk2. (pnas.org)
  • This docking site is critical for cyclin A-cdk2 phosphorylation of substrates containing RXL motifs, but not for phosphorylation of histone H1. (pnas.org)
  • In recent years, however, cyclins have been shown to play a role in substrate selection, as different substrate preferences are observed for cdk2 bound to cyclin E or cyclin A and for cdc2 bound to cyclin A or cyclin B ( 9 - 11 ). (pnas.org)
  • In this work we have investigated the mechanism of substrate recognition by cyclin A-cdk2. (pnas.org)
  • Cyclin A associates with cdk2 during S-phase and cdc2 during G 2 ( 17 - 20 ). (pnas.org)
  • Numerous observations suggest that cyclin A-cdk2 is involved in controlling DNA replication. (pnas.org)
  • It will be important to understand how cyclin A-cdk2 recognizes its substrates in order to understand its function in cell cycle progression. (pnas.org)
  • We examined the crystal structure of cyclin A-cdk2 seeking clues for the role of cyclin A in substrate recognition ( 30 ). (pnas.org)
  • Indeed, the crystal structure of cyclin A-cdk2 in complex with the inhibitory protein, p27, reveals that this hydrophobic patch on cyclin A contacts the RNLFG sequence in p27, termed a Cy or RXL motif ( 33 , 34 ) that is conserved between both substrates and inhibitors of cyclin-cdks ( 33 - 37 ). (pnas.org)
  • We have made hydrophobic to alanine mutations in cyclin A based on this crystal structure to investigate the role of the hydrophobic patch in cyclin A-cdk2 function. (pnas.org)
  • We find that this hydrophobic patch mediates binding to RXL-containing proteins and that this binding is important for phosphorylation of a subset of substrates of cyclin A-cdk2. (pnas.org)
  • Thus, our results suggest a mechanism for substrate recruitment to cdk2 by cyclin A. (pnas.org)
  • 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. (nih.gov)
  • 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). (nih.gov)
  • To address this apparent paradox, we examined possible predictors of the sensitivity of 10 breast cancer cell lines to erlotinib in light of cyclin-dependent kinase 2 (CDK2), considered the farthest downstream kinase that controls cell cycling in the EGFR signaling pathway. (aacrjournals.org)
  • Reports that cell lines showing sensitivity to EGFR-TKIs showed G 1 arrest after treatment with EGFR-TKIs ( 11 - 13 ) led us to study the potential relationship between cyclin-dependent kinases (CDK), particularly CDK2 ( 12 , 13 ) and erlotinib sensitivity. (aacrjournals.org)
  • CDK2 regulates the G 1 -S phase transition and, within the EGFR signaling pathway, is the farthest downstream molecule with known kinase activity ( 13 - 15 ). (aacrjournals.org)
  • Taking its origin from of OTAVA s in-house collection of 500,000 compounds, this CDK2 focused library is composed of 1281 compounds which were selected by computational estimation of their interaction with one specific member in a protein kinase family (sharp-focusing approach). (hum-molgen.org)
  • Phosphorylation of GATA3 Thr-156 was detected in mouse thymocytes, and cyclin-dependent kinase 2 (CDK2) was identified as a respondent for phosphorylation at Thr-156. (asm.org)
  • Cyclin-dependent kinase 7 (CDK7) is the catalytic subunit of the metazoan CDK-activating kinase (CAK), which activates CDKs, such as CDC2 and CDK2, through phosphorylation of a conserved threonine residue in the T loop. (elsevier.com)
  • The ability of CDC2 or CDK2 and CDK7 to phosphorylate each other but not themselves implies that each kinase can discriminate among closely related sequences and can recognize a substrate site that diverges from its usual preferred site. (elsevier.com)
  • Surprisingly, the hybrid enzyme, CDK2-7, was efficiently activated in cyclin A-dependent fashion by CDK7 but not at all by CDK2. (elsevier.com)
  • Tat itself is phosphorylated by CDK2, and inhibition of CDK2 by small interfering RNA, the iron chelator 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311), and the iron chelator deferasirox (ICL670) inhibits HIV-1 transcription. (isharonline.org)
  • Our prior work discovered that lung cancer cells undergo anaphase catastrophe in response to inhibition of cyclin-dependent kinase 2 (CDK2), followed by apoptosis and reduced growth. (elsevier.com)
  • Overexpression of CP110, which is a mediator of CDK2 inhibitor-induced anaphase catastrophe (and a CDK1 and 2 phosphorylation substrate), antagonized anaphase catastrophe and apoptosis following dinaciclib treatment. (elsevier.com)
  • Derepression of E2F results from a series of complex phosphorylation events mediated by cyclin D/cdk4 and cyclin E/cdk2. (elsevier.com)
  • We have employed a novel 3-substituted indolinone compound, 3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516), which selectively inhibits cdk2 activity (Lane et al. (elsevier.com)
  • These findings delineate a previously undescribed mechanism for SU9516-mediated cell growth arrest through down-regulation of cyclin D1, inhibition of cdk2 levels and activity, and pan-sequestration of E2F. (elsevier.com)
  • Of these, compound 2 bound CDK2 with an EC50 value of 3 μM and inhibited the proliferation of MDA-MB231 and ZR-75-1 breast cancer cells with IC50 values of approximately 20 μM, while compound 4 had an EC50 value of 71 μM and IC50 values around 4 μM. (unimore.it)
  • The protein encoded by this gene is a cyclin-dependent kinase 2 (CDK2) -associated protein which is thought to negatively regulate CDK2 activity by sequestering monomeric CDK2, and targeting CDK2 for proteolysis. (genecards.org)
  • specific inhibitor of the cell-cycle kinase CDK2. (genecards.org)
  • This G1 arrest is associated with a dramatic decrease in the protein levels of Cdk2 and cyclin E correlated with an inhibition of the Cdk2 kinase activity. (biomedsearch.com)
  • Kinetic and crystallographic analyses of CDK2-cyclin A complexes reveal that this inhibitory mechanism operates through steric blockade of peptide substrate binding and through the creation of an environment that favors a non-productive conformation of the terminal group of ATP. (northwestern.edu)
  • Sustained CDK2 catalytic activity, typically associated with megakaryocyte endomitosis, was dramatically decreased in TPA-stimulated Evi1-expressing HEL cells because of significantly reduced levels of cyclin A. Therefore, enforced Evi1 expression could inhibit megakaryocyte differentiation although retention of some characteristic molecular changes, in combination with a block in endomitosis and altered morphology, suggest a defect in lineage progression. (gcu.ac.uk)
  • La quinasa dependiente de ciclina 2 , también conocida como Cdk2 , es una proteína codificada en humanos por el gen cdk2 . (wikipedia.org)
  • El papel de esta proteína en la transición G1/S ha sido cuestionado recientemente al haberse observado que la transición G1/S se producía sin problemas en células que no poseían Cdk2. (wikipedia.org)
  • Se ha observado que, en melanocitos , la expresión del gen cdk2 es regulada por el factor de transcripción asociado con microftalmia . (wikipedia.org)
  • A network of interacting proteins controls the activity of cyclin dependent kinase 2 (Cdk2) and governs the entry of higher eukaryotic cells into S phase. (wustl.edu)
  • Zhao J, Kennedy BK, Lawrence BD, Barbie DA, Matera AG, Fletcher JA, Harlow E. NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription. (proteopedia.org)
  • Substituted guanines and pyrimidines were tested as inhibitors of cyclin B1/CDK1 and cyclin A3/CDK2 and soaked into crystals of monomeric CDK2. (proteopedia.org)
  • Downstream events, such as activation of cyclin E-Cdk2 and cyclin A-Cdk2 complexes, are delayed and reduced in magnitude. (asm.org)
  • We determined site-specific stoichiometry of more than 5000 sites and found that most of the up-regulated sites phosphorylated by cyclin-dependent kinase 1 (CDK1) or CDK2 were almost fully phosphorylated in mitotic cells. (nih.gov)
  • 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. (springer.com)
  • Cyclins, together with the p34 (cdc2) or cdk2 kinases, form the Maturation Promoting Factor (MPF). (embl.de)
  • The aim of presented study was to determine the effect of ABT-737 inhibitor of anti-apoptotic proteins Bcl-2, Bcl-XL and Bcl-w as well as cyclin-dependent kinase 2 (CDK2) inhibitor SU9516 alone and in combination with ABT-737 on survival of colorectal cell lines HT29 and Caco-2. (bireme.br)
  • Our findings provide a rationale for clinical use of Bcl-2 family inhibitors in combination with CDK2 inhibitors for treatment of Mcl-1-dependent colorectal tumours associated with expression of Bcl-2, Bcl-XL and Bcl-w proteins. (bireme.br)
  • However, their research also showed that treating breast cancer cells with a cyclin-dependent kinase 2 (CDK2) inhibitor can reverse letrozole resistance. (scienceblog.com)
  • After confirming that the LMW forms of cyclin E suppress the anti-proliferative effects of letrozole, the researchers examined whether a CDK2 inhibitor could reverse the drug resistance in the unresponsive breast cancer cells. (scienceblog.com)
  • We challenged the aromatase-overexpressing cells with either the wild-type or the low forms of cyclin E and then treated them with the CDK2 inhibitor roscovitine," Keyomarsi said. (scienceblog.com)
  • Crystal structures of inhibitors with these bicyclic cores and two more related ones show that all but one have a common binding mode featuring two hydrogen bonds (H-bonds) to the backbone of the kinase hinge region. (rcsb.org)
  • Inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinases, such as erlotinib and gefitinib, have not been very effective in the treatment of breast cancer although many breast cancer cells express EGFR. (aacrjournals.org)
  • Evaluation of 3-Carboxy-4(1H)-quinolones as Inhibitors of Human Protein Kinase CK2. (hum-molgen.org)
  • OTAVA provides compound libraries for screening and it offers custom synthesis and molecular modeling services, targeted compound libraries and protein kinase inhibitors, prescreened anticancer compounds, peptide and chromogenic substrates. (hum-molgen.org)
  • Fernanda Canduri and Walter Filgueira de Azevedo Jr., " Structural Basis for Interaction of Inhibitors with Cyclin-Dependent Kinase 2", Current Computer-Aided Drug Design (2005) 1: 53. (eurekaselect.com)
  • Allosteric targeting of protein kinases via displacement of the structural αC helix with type III allosteric inhibitors is currently gaining a foothold in drug discovery. (unimore.it)
  • Cellular proliferation is driven by cyclin-dependent kinases (CDKs) with kinase inhibitors (for example, p27) applying the breaks. (nature.com)
  • Cellular proliferation is driven by the periodic association of cyclin-dependent kinases (CDKs) and their partner cyclins and controlled by kinase inhibitors, for example p27, and dysregulation of this finely orchestrated process is a characteristic of cancer. (nature.com)
  • Previously, we reported that inhibitors of cyclin-dependent kinases (CDKs) prevented cytosolic stress granule accumulation of TDP-43, correlating with depletion of heterogeneous ribonucleoprotein (hnRNP) K from stress granules. (edu.au)
  • AIMS: Cyclin-dependent kinase inhibitors (CDKIs) play a critical role in negatively regulating the proliferation of cardiomyocytes, although their role in cardiac differentiation remains largely undetermined. (biomedsearch.com)
  • Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles. (proteopedia.org)
  • The Kinase Enzyme Systems allow you to easily screen and profile kinase inhibitors. (promega.com)
  • Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. (nature.com)
  • In thisreview, we focus our attention on cyclin-cyclin-dependent kinase complexes,cyclin kinase inhibitors, genes of the retinoblastoma family, p53 and N-Myc, and we aim to summarize the latest evidence indicating their involvement in thecontrol of the cell cycle and induction of differentiation in different celltypes of the peripheral and central nervous systems. (embl.de)
  • The scheduled activity of the cdks, which allows orderly transition between cell cycle phases, is controlled by their association with cyclins and cdk inhibitors, by their state of phosphorylation, and by ubiquitin-mediated proteolysis. (jci.org)
  • As malignant cells evolve, both genetic and epigenetic mechanisms commonly affect the expression of cell cycle regulatory proteins, causing overexpression of cyclins and loss of expression of cdk inhibitors. (jci.org)
  • The crucial role of the cdks has prompted great interest in the development of specific kinase inhibitors that would be expected to block cell cycle progression and induce growth arrest. (jci.org)
  • This protein kinase is highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, also known as Cdk1 in humans. (wikipedia.org)
  • controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. (uniprot.org)
  • Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression, controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. (biomol.com)
  • Furthermore, MCF-7 cells treated with IV-2 showed increased Cdk1 kinase activity and a decrease in Cdk1 tyrosine phosphorylation, indicating that IV-2 did not directly inhibit Cdk1 or Cdc25 activities. (aspetjournals.org)
  • Cyclin Dependent Kinase 1 (p34 Protein Kinase or Cell Division Protein Kinase 1 or Cell Division Control Protein 2 Homolog or CDK1 or EC 2.7.11.22 or EC 2.7.11.23) pipeline Target constitutes close to 7 molecules. (researchmoz.us)
  • The latest report Cyclin Dependent Kinase 1 - Pipeline Review, H2 2017, outlays comprehensive information on the Cyclin Dependent Kinase 1 (p34 Protein Kinase or Cell Division Protein Kinase 1 or Cell Division Control Protein 2 Homolog or CDK1 or EC 2.7.11.22 or EC 2.7.11.23) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (researchmoz.us)
  • It also reviews key players involved in Cyclin Dependent Kinase 1 (p34 Protein Kinase or Cell Division Protein Kinase 1 or Cell Division Control Protein 2 Homolog or CDK1 or EC 2.7.11.22 or EC 2.7.11.23) targeted therapeutics development with respective active and dormant or discontinued projects. (researchmoz.us)
  • Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine kinase, and is a key player in cell cycle regulation. (wikipedia.org)
  • Cdk1 is comprised mostly by the bare protein kinase motif, which other protein kinases share. (wikipedia.org)
  • Cdk1, like other kinases, contains a cleft in which ATP fits. (wikipedia.org)
  • In addition to this catalytic core, Cdk1, like other cyclin-dependent kinases, contains a T-loop, which, in the absence of an interacting cyclin, prevents substrate binding to the Cdk1 active site. (wikipedia.org)
  • Cdk1 also contains a PSTAIRE helix, which, upon cyclin binding, moves and rearranges the active site, facilitating Cdk1 kinase activities. (wikipedia.org)
  • When bound to its cyclin partners, Cdk1 phosphorylation leads to cell cycle progression. (wikipedia.org)
  • however, when phosphorylated by Cln3-Cdk1, Whi5 is ejected from the nucleus, allowing for transcription of the G1/S regulon, which includes the G1/S cyclins Cln1,2. (wikipedia.org)
  • G1/S cyclin-Cdk1 activity leads to preparation for S phase entry (e.g., duplication of centromeres or the spindle pole body), and a rise in the S cyclins (Clb5,6 in S. cerevisiae). (wikipedia.org)
  • Cln1,2 and/or Clb5,6-Cdk1 complex activity leads to a sudden drop in Sic1 levels, allowing for coherent S phase entry. (wikipedia.org)
  • Clb1, 2, 3 and 4) in complex with Cdk1 leads to spindle assembly and sister chromatid alignment. (wikipedia.org)
  • Cdk1 phosphorylation also leads to the activation of the ubiquitin-protein ligase APCCdc20, an activation which allows for chromatid segregation and, furthermore, degradation of M-phase cyclins. (wikipedia.org)
  • Most obviously, Cdk1 is regulated by its binding with its cyclin partners. (wikipedia.org)
  • furthermore, cyclins impart specificity to Cdk1 activity. (wikipedia.org)
  • Furthermore, cyclins can target Cdk1 to particular subcellular locations. (wikipedia.org)
  • In addition to regulation by cyclins, Cdk1 is regulated by phosphorylation. (wikipedia.org)
  • Cdk1-cyclin complexes are also governed by direct binding of Cdk inhibitor proteins (CKIs). (wikipedia.org)
  • Multisite phosphorylation, by Cdk1-Cln1/2, of Sic1 is thought to time Sic1 ubiquitination and destruction, and by extension, the timing of S-phase entry. (wikipedia.org)
  • Inhibition of cyclin-dependent kinase 1 (CDK1) activity by Tyr-15 phosphorylation directly regulates entry into mitosis and is an important element in the control of the unperturbed cell cycle. (northwestern.edu)
  • At the cellular level, the process is controlled by different levels of cyclin-dependent kinases (Cdks) and their partner cyclins. (wikipedia.org)
  • An important question in the cell cycle field is how cyclin-dependent kinases (cdks) target their substrates. (pnas.org)
  • Thus, we define a mechanism by which cyclins can recruit substrates to cdks, and our results support the notion that a high local concentration of substrate provided by a protein-protein interaction distant from the active site is critical for phosphorylation by cdks. (pnas.org)
  • A number of studies have shown that cdks are active only after binding to a cyclin partner. (pnas.org)
  • In addition, a number of substrates have been shown to form complexes with cyclin-cdks, suggesting that high-affinity protein-protein interactions play a role in cdk substrate recognition ( 12 - 16 ). (pnas.org)
  • Cell cycle progression is tightly controlled by the activity of cyclin-dependent kinases (CDKs). (eurekaselect.com)
  • CDKs are inactive as monomers, and activation requires binding to cyclins, a diverse family of proteins whose levels oscillate during the cell cycle, and phosphorylation by CDK-activating kinase (CAK) on a specific threonine residue. (eurekaselect.com)
  • The closest relatives of MAPKs are the cyclin-dependent kinases (CDKs). (wikipedia.org)
  • Cyclins are eukaryotic proteins that play an active role in controlling nuclear cell division cycles [ ( PUBMED:12910258 ) ], and regulate cyclin dependent kinases (CDKs). (embl.de)
  • Central players are the cyclin-dependent kinases (cdks), which govern the initiation, progression, and completion of cell cycle events. (jci.org)
  • It is a catalytic subunit of the cyclin-dependent kinase complex, whose activity is restricted to the G1-S phase of the cell cycle, where cells make proteins necessary for mitosis and replicate their DNA. (wikipedia.org)
  • Studies using Myc and Max proteins with reciprocal complementary mutations in their leucine zippers have shown that heterodimeric complex formation is required for cell cycle progression, apoptosis, and transformation ( 2 , 4 ). (asm.org)
  • This protein and neuron-specific CDK5 activator CDK5R1/p39NCK5A both share limited similarity to cyclins, and thus may define a distinct family of cyclin-dependent kinase activating proteins. (wikipedia.org)
  • The proteins that N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(2-naphthyl)acetamide targets include cyclin-A2 and cyclin-dependent kinase 2. (drugbank.ca)
  • Cyclins are a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (Cdk) enzymes. (embl.de)
  • There are 14939 Cyclin_C domains in 14900 proteins in SMART's nrdb database. (embl.de)
  • Taxonomic distribution of proteins containing Cyclin_C domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with Cyclin_C domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing Cyclin_C domain in the selected taxonomic class. (embl.de)
  • Colorectal carcinoma (CRC) that represents one of the major causes for cancer-related death in humans is often associated with over-expression of anti-apoptotic proteins of Bcl-2 family. (bireme.br)
  • Cyclin E is one of the proteins that regulates the cell cycle, influencing how rapidly a cell passes through the four phases and divides. (scienceblog.com)
  • Eukaryotic protein kinases (PKs) are a large family of proteins critical for cellular response to external signals, acting as molecular switches. (biochemj.org)
  • Cyclin-dependent kinase-like 2 (Cdkl2) is a cdc2-related serine/threonine protein kinase that is postnatally expressed in various brain regions, including the cerebral cortex, entorhinal cortex, hippocampus, amygdala, and dorsal thalamus. (frontiersin.org)
  • This gene encodes a member of a family of serine/threonine protein kinases that participate in cell cycle regulation. (creativebiomart.net)
  • Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase 4 or Cell Division Protein Kinase 9 or Serine/Threonine Protein Kinase PITALR or CDK9 or EC 2.7.11.22 or EC 2.7.11.23) - Cyclin-dependent kinase 9 (CDK9) is a cyclin-dependent kinase associated with P-TEFb. (reportsnreports.com)
  • Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase 4 or Cell Division Protein Kinase 9 or Serine/Threonine Protein Kinase PITALR or CDK9 or EC 2.7.11.22 or EC 2.7.11.23) pipeline Target constitutes close to 26 molecules. (reportsnreports.com)
  • It also reviews key players involved in Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase 4 or Cell Division Protein Kinase 9 or Serine/Threonine Protein Kinase PITALR or CDK9 or EC 2.7.11.22 or EC 2.7.11.23) targeted therapeutics development with respective active and dormant or discontinued projects. (reportsnreports.com)
  • This gene product is a member of a large family of CDC2-related serine/threonine protein kinases. (genecards.org)
  • A mitogen-activated protein kinase ( MAPK or MAP kinase ) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase ). (wikipedia.org)
  • MAP2 kinases in turn, are also activated by phosphorylation, by a number of different upstream serine-threonine kinases ( MAP3 kinases ). (wikipedia.org)
  • The encoded protein is the catalytic subunit of the cyclin-dependent protein kinase complex, which regulates progression through the cell cycle. (creativebiomart.net)
  • This kinase was found to be a component of the multiprotein complex TAK/P-TEFb, which is an elongation factor for RNA polymerase II-directed transcription and functions by phosphorylating the C-terminal domain of the largest subunit of RNA polymerase II. (reportsnreports.com)
  • This protein forms a complex with and is regulated by its regulatory subunit cyclin T or cyclin K. HIV-1 Tat protein was found to interact with CDK9 and cyclin T, which suggested a possible involvement of this protein in AIDS. (reportsnreports.com)
  • Full activation of CDK7 requires association with a positive regulatory subunit, cyclin H, and phosphorylation of a conserved threonine residue at position 170 in its own T loop. (elsevier.com)
  • Patients with biallelic mutations in the Cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (CDK5RAP2) gene suffer from autosomal recessive primary microcephaly type 3 (MCPH3) and intellectual disability at birth. (fu-berlin.de)
  • Biallele Mutationen im Cyclin-dependent kinase 5 regulatory subunit-associated protein 2 Gen (CDK5RAP2) verursachen die Autosomal rezessive primäre Mikrozephalie Typ 3 (MCPH3). (fu-berlin.de)
  • Cyclin-dependent kinase (CDK)-cyclin complexes require phosphorylation on the CDK subunit for full activation of their Ser/Thr protein kinase activity. (proteopedia.org)
  • 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. (springer.com)
  • Activation of cyclin-dependent kinases requires association of the enzyme with a regulatory subunit referred to as a cyclin. (cathdb.info)
  • The induction of cyclin D2 and the decrease in p27 were not inhibited by UP, whereas the induction of cyclin E, cyclin A, cyclin-dependent kinase-2, and cyclin-dependent kinase-4 was strongly inhibited, potentially explaining the inhibition of retinoblastoma protein phosphorylation. (jimmunol.org)
  • Treatment effects were time-dependent, demonstrating greater inhibition at 48hr versus 24hr in HT-29 cells. (elsevier.com)
  • Recent reports from our lab suggest that in the presence of diabetes mellitus, elevation of extracellular signal response kinase activity may promote decreased p27 Kip1 mRNA and produce a relative resistance to mTOR inhibition. (mdpi.com)
  • In this study, antioxidant and inhibition of senescence effects of embelin were examined using hydrogen peroxide (H 2 O 2 )-induced cellular aging model of human dermal fibroblast. (springer.com)
  • Fig. 2: Maintenance of AURKA is associated with resistance to PI3K inhibition. (nature.com)
  • Fig. 5: Aurora kinase co-inhibition durably suppresses mTORC1 signaling and alters the BAX/BCL2 ratio. (nature.com)
  • mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. (nature.com)
  • 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. (nature.com)
  • Inhibition of tau phosphorylating protein kinase cdk5 prevents β-amyloid-induced neuronal death. (springer.com)
  • Involvement of p38 mitogen-activated protein kinase in basic fibroblast growth factor-induced interl. (biomedsearch.com)
  • The first mitogen-activated protein kinase to be discovered was ERK1 ( MAPK3 ) in mammals. (wikipedia.org)
  • The largest defect observed in c- myc −/− cells is a 12-fold reduction in the activity of cyclin D1-Cdk4 and -Cdk6 complexes during the G 0 -to-S transition. (asm.org)
  • In exponentially cycling cells the absence of c-Myc reduces coordinately the activities of all cyclin-cyclin-dependent kinase complexes. (asm.org)
  • 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. (springer.com)
  • We now examined the effects of IV-2 on cell cycle progression. (aspetjournals.org)
  • These data suggest that the thioredoxin inhibitor IV-2, despite its simple structure, is able to target redox-sensitive processes that are critical for cell cycle progression through mitosis. (aspetjournals.org)
  • The results are also consistent with a role of thioredoxin regulating cell cycle progression through G 2 /M. (aspetjournals.org)
  • Targeted degradation of the cyclin-dependent kinase inhibitor ICK4/KRP6 by RING-type E3 ligases is essential for mitotic cell cycle progression during Arabidopsis gametogenesis. (nextbio.com)
  • This phenomenon was accompanied by down-regulation of CDC25A, a phosphatase regulating progression of cell cycle through S-phase, and PKR-dependent hyper-phosphorylation of eIF2α, an inhibitor of CDC25 translation. (portlandpress.com)
  • See reference mRNA sequence for the CDKB1;2 gene (NM_129419.3). (nih.gov)
  • See 4 reference sequence protein isoforms for the CDKB1;2 gene. (nih.gov)
  • The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein kinases. (wikipedia.org)
  • The retinoblastoma (RB) and cyclin-dependent kinase inhibitor 2/multiple tumor suppressor gene 1 ( CDKN2/MTS1 ) tumor suppressor genes play important roles in the regulation of the cell cycle. (aacrjournals.org)
  • Recently, a putative 9p21 tumor suppressor gene, the cyclin dependent kinase inhibitor 2 ( CDKN2 ) or p16 gene, has been shown to be deleted, mutated, or rear-ranged in a high percentage of sporadic melanoma cell lines, as well as mutated in the germline of a proportion of familial melanoma patients. (aacrjournals.org)
  • CDKL2 (Cyclin Dependent Kinase Like 2) is a Protein Coding gene. (genecards.org)
  • GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity . (genecards.org)
  • Cyclin-dependent kinase 5 activator 2 is an enzyme that in humans is encoded by the CDK5R2 gene . (wikipedia.org)
  • The protein encoded by this gene is a neuron-specific activator of CDK5 kinase. (wikipedia.org)
  • This article on a gene on human chromosome 2 is a stub . (wikipedia.org)
  • These observations indicate that the synthesis of PI3,5P 2 on the vacuole/lysosome is tightly regulated and suggest that PI3,5P 2 may function in an early defense pathway that acts before changes in gene expression. (rupress.org)
  • 3. The method of claim 2 wherein the substances inhibits IBABP-L gene expression. (freepatentsonline.com)
  • Global Markets Direct's, 'Cyclin-Dependent Kinase 2 (p33 Protein Kinase or cdc2-Related Protein Kinase or EC 2.7.11.22) - Pipeline Review, H1 2016', provides in depth analysis on Cyclin-Dependent Kinase 2 (p33 Protein Kinase or cdc2-Related Protein Kinase or EC 2.7.11.22) targeted pipeline therapeutics. (reportsnreports.com)
  • Additionally, the report provides an overview of key players involved in Cyclin-Dependent Kinase 2 (p33 Protein Kinase or cdc2-Related Protein Kinase or EC 2.7.11.22) targeted therapeutics development and features dormant and discontinued projects. (reportsnreports.com)
  • Fingerprint Dive into the research topics of 'How tyrosine 15 phosphorylation inhibits the activity of cyclin-dependent kinase 2-cyclin A'. Together they form a unique fingerprint. (northwestern.edu)
  • The significance of this movement is that it brings the side chain of Glu 51, which belongs to a triad of catalytic site residues conserved in all eukaryotic kinases, into the catalytic site. (wikipedia.org)
  • OSI Pharmaceuticals, Inc., and Genentech, Inc.) is an orally available quinazolinamine that competes with ATP for binding with the intracellular catalytic domain of EGFR tyrosine kinase (EGFR-TK) to inhibit the phosphorylation of EGFR-TK. (aacrjournals.org)
  • Characterization of the new immunosuppressive drug undecylprodigiosin in human lymphocytes: retinoblastoma protein, cyclin-dependent kinase-2, and cyclin-dependent kinase-4 as molecular targets. (jimmunol.org)
  • HOUSTON - Overexpression of low-molecular-weight (LMW-E) forms of the protein cyclin E renders the aromatase inhibitor letrozole ineffective among women with estrogen-receptor-positive (ER+) breast cancers, researchers from The University of Texas M. D. Anderson Cancer Center report in Clinical Cancer Research . (scienceblog.com)
  • In tumor cells, cyclin E is converted to low-molecular weight forms, an event that does not occur in normal cells. (scienceblog.com)
  • These findings demonstrate Cdk5 phosphorylation-dependent destabilization of specific MEF2 isoforms as an important regulatory mechanism in mediating neurotoxin-induced death. (jneurosci.org)
  • regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. (uniprot.org)
  • Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis, regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. (biomol.com)
  • Cyclin-dependent kinase 5 regulates PSD-95 ubiquitination in neurons. (springer.com)
  • We show that Pho85/CDK5 directly phosphorylates and positively regulates the PI3P-5 kinase Fab1/PIKfyve complex and provide evidence that this regulation is conserved in mammalian cells. (rupress.org)
  • The structure is bi-lobate, like that of the cyclic AMP-dependent protein kinase, but contains a unique helix-loop segment that interferes with ATP and protein substrate binding and probably plays a key part in the regulation of all cyclin-dependent kinases. (nih.gov)
  • Impaired substrate binding by the cyclin is the cause of the defect in RXL substrate phosphorylation, because phosphorylation can be rescued by restoring a cyclin A-substrate interaction in a heterologous manner. (pnas.org)
  • Restoring substrate binding to cyclin A in a heterologous manner is sufficient to rescue phosphorylation even with mutations in the hydrophobic patch. (pnas.org)
  • Our results suggest that the primary amino acid sequence of the T loop plays only a minor role, if any, in determining the specificity of cyclin-dependent CAKs for their CDK substrates and that protein-protein interactions involving sequences outside the T loop can influence substrate specificity both positively and negatively. (elsevier.com)
  • They provide all the optimized components (enzyme, preferred substrate, required cofactors, buffer) that you need to generate a kinase selectivity profile for a compound. (promega.com)
  • Most MAPKs have a number of shared characteristics, such as the activation dependent on two phosphorylation events, a three-tiered pathway architecture and similar substrate recognition sites. (wikipedia.org)
  • HIV-1 transcription is activated by HIV-1 Tat protein, which recruits cyclin-dependent kinase 9 (CDK9)/cyclin T1 and other host transcriptional coactivators to the HIV-1 promoter. (isharonline.org)
  • activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. (uniprot.org)
  • In addition, the conserved hydrophobic patch is important for cyclin A function in cells, contributing to cyclin A's ability to drive cells out of the G 1 phase of the cell cycle. (pnas.org)
  • Third, overexpression of cyclin A in cells accelerates exit from G 1 phase ( 27 , 28 ). (pnas.org)
  • B, SW620 cells were arrested in mitosis with nocodazole treatment for 16 h before treatment with AZD5438 for 2 h. (aacrjournals.org)
  • C, the kinetics ( black columns ) and recovery ( gray columns ) of pRb phosphorylation (pSer 249 /pThr 252 ) was further investigated in SW620 cells by exposing cells to 2 μmol/L AZD5438 for up to 2 h. (aacrjournals.org)
  • The redox-active, asymmetrical 1-methylpropyl-2-imidazolyl disulfide (IV-2) has previously been shown to react with and inhibit thioredoxin activity in vitro, the proliferation of human tumor cells in culture, and the growth of tumors in mice. (aspetjournals.org)
  • In synchronized tsFT210 mouse mammary carcinoma cells, IV-2 halted cells in mitosis. (aspetjournals.org)
  • In asynchronously growing MCF-7 human breast cancer cells, IV-2 exclusively and irreversibly blocked cells in G 2 /M at concentrations that correlated with its growth inhibitory activity. (aspetjournals.org)
  • Both the 44- and 42-kDa forms of the MAP-kinase protein were expressed at similar levels in young and senescent cells. (isharonline.org)
  • Lactoferrin inhibits G1 cyclin-dependent kinases during growth arrest of human breast carcinoma cells. (biomedsearch.com)
  • 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. (nih.gov)
  • An analysis of cyclin-dependent kinase complex regulators revealed increased expression of p27 KIP1 and decreased expression of Cdk7 in c- myc −/− cells. (asm.org)
  • G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). (embl.de)
  • Cyclin-dependent kinase 2 inhibitor SU9516 increases sensitivity of colorectal carcinoma cells Caco-2 but not HT29 to BH3 mimetic ABT-737. (bireme.br)
  • We have shown that both Caco-2 and HT29 cells that are relatively resistant to ABT-737 are also partially sensitive to SU9516, which increased sensitivity of Caco-2 but not HT29 cells to ABT-737. (bireme.br)
  • Increased sensitivity of Caco-2 cells to ABT-737 after addition of SU9516 correlated well with SU9516-induced decrease of Mcl-1 expression while we have not observed downregulation of Mcl-1 after the treatment of HT29 cells with SU9516. (bireme.br)
  • Cisplatin or LA-12 enhance killing effects of TRAIL in prostate cancer cells through Bid-dependent stimulation of mitochondrial apoptotic pathway but not caspase-10. (bireme.br)
  • Wang et al uncovered that 2-O-Methylmagnolol upregulated the long non-coding RNA, GAS5 , and enhanced apoptosis in skin cancer cells ( 12 ). (spandidos-publications.com)
  • SFN has also been reported to sensitize cancer cells to imatinib- and tumor necrosis factor-related apoptosis inducing ligand-induced apoptosis, via a reactive oxygen species (ROS)-dependent pathway ( 8 , 9 ), suggesting potential therapeutic value as an adjunct to current cancer therapies. (spandidos-publications.com)
  • Cyclin-dependent kinase 5 (Cdk5) mediates neurotoxic effects by phosphorylating and inhibiting MEF2. (jneurosci.org)
  • How Cdk5-dependent phosphorylation reduces MEF2 transactivation activity remained unknown. (jneurosci.org)
  • In contrast to MEF2A and MEF2D, MEF2C is not phosphorylated by Cdk5 after glutamate exposure and, therefore, resistant to neurotoxin-induced caspase-dependent degradation. (jneurosci.org)
  • The convergence of Cdk5 phosphorylation-dependent caspase-mediated degradation of nuclear survival factors exemplified by MEF2 may represent a general process applicable to the regulation of other survival factors under diverse neurotoxic conditions. (jneurosci.org)
  • Cyclin-dependent kinase 5 (Cdk5) is a proline-directed kinase the activity of which is dependent on association with its neuron-specific activators, p35 and p39. (mblwhoilibrary.org)
  • Additionally, Cdk5 phosphorylates RasGRF2 both in vitro and in vivo, leading to a decrease in Rac-guanidine exchange factor activity and a subsequent reduction in extracellular signal-regulated kinase 1/2 activity. (mblwhoilibrary.org)
  • It associates with CDK5 to form an active kinase. (wikipedia.org)
  • 1995 ). CDK5/p35 is the first example of a CDC2-like kinase with neuronal function. (springer.com)
  • Cyclin-dependent kinase 5 (CDK5) controls melanoma cell motility, invasiveness, and metastatic spread-identification of a promising novel therapeutic target. (springer.com)
  • In this study, we show that in yeast, the cyclin-dependent kinase Pho85/CDK5 provides protection against hyperosmotic stress and acts before long-term adaptation provided by Hog1. (rupress.org)
  • Furthermore, we show that mammalian CDK5-CDK5R1/p35, homologues of yeast Pho85-Pho80, directly phosphorylate human PIKfyve in vitro and regulate the synthesis of PI3,5P 2 in mouse fibroblasts. (rupress.org)
  • It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. (ucdenver.edu)
  • CDKN2 encodes a M r 16,000 protein (p16) that plays a key role in cell cycle control by binding to the cyclin-dependent kinase 4 enzyme and inhibiting its ability to phosphorylate critical substrates necessary for transition past the G 1 phase of the cell cycle. (aacrjournals.org)
  • This protein associates with and regulated by other subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A), and p27Kip1 (CDKN1B). (creativebiomart.net)
  • Cyclin levels oscillate throughout the cell cycle and are restricted spatially within a cell, thus limiting cdk activity both temporally and spatially. (pnas.org)
  • This evidence suggests that the Cdkl kinase family might be involved in behavioral modification, activity-dependent synaptic plasticity, and learning. (frontiersin.org)
  • The kinase activity is controlled by cyclin accumulation and destruction through the cell cycle. (researchmoz.us)
  • this phosphorylation is thought to alter ATP orientation, preventing efficient kinase activity. (wikipedia.org)
  • Understanding how kinase activity modulates TDP-43 accumulation may provide new pharmacological targets for disease intervention. (edu.au)
  • How tyrosine 15 phosphorylation inhibits the activity of cyclin-dependent kinase 2-cyclin A . Journal of Biological Chemistry , 282 (5), 3173-3181. (northwestern.edu)
  • Embelin decreased the SA-β-galactosidase activity in a dose-dependent manner in H 2 O 2 -treated HDFs. (springer.com)
  • Furthermore, using deleted and mutant forms of Xic1, we show that neither its abilities to inhibit the cell cycle nor the great majority of CDK kinase activity are essential for Xic1's function in cardiomyocyte differentiation, an activity that resides in the N-terminus of the molecule. (biomedsearch.com)
  • CONCLUSION: Altogether, our results demonstrate that the CDKI Xic1 is required in Xenopus cardiac differentiation, and that this function is localized at its N-terminus, but it is distinct from its ability to arrest the cell cycle and inhibit overall CDK kinase activity. (biomedsearch.com)
  • p35/cyclin-dependent kinase 5 phosphorylation of ras guanine nucleotide releasing factor 2 (RasGRF2) mediates Rac-dependent Extracellular Signal-regulated kinase 1/2 activity, altering RasGRF2 and microtubule-associated protein 1b distribution in neurons. (mblwhoilibrary.org)
  • Because MAP2 kinases display very little activity on substrates other than their cognate MAPK, classical MAPK pathways form multi-tiered, but relatively linear pathways. (wikipedia.org)
  • 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. (springer.com)
  • The mechanism behind this is that the low forms of cyclin E increase the activity of the cyclin E complex, and this complex is what mediates the negative effects. (scienceblog.com)
  • Of the seven patients who had a recurrence, six had high levels of cyclin E activity. (scienceblog.com)
  • Esquema de las rutas de transducción de señales implicadas en el proceso de apoptosis . (wikipedia.org)
  • Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. (springer.com)
  • The success of the cell division process is dependent on the precise regulation of processes at both cellular and tissue levels. (wikipedia.org)
  • The heterogeneity of kinases involved in phospho-regulation provides a fundamental basis for the sequential biochemical reactions that underlie the mechanisms of synaptic plasticity. (frontiersin.org)
  • Moreover, this regulation is particularly crucial in yeast for the stress-induced transient elevation of PI3,5P 2 . (rupress.org)
  • It is the sequential activation and inactivation of cyclin-dependent kinases, through the periodic synthesis and destruction of cyclins, that provides the primary means of cell-cycle regulation. (cathdb.info)
  • This action blocks downstream signal transduction and inhibits the tumorigenic effects associated with ligand-dependent and ligand-independent EGFR activation ( 1 , 2 ). (aacrjournals.org)
  • UP inhibits only partially the expression of IL-2R, suggesting that the major target of UP is localized downstream from the interaction between IL-2 and its receptor. (jimmunol.org)
  • p27 Kip1 is a cyclin dependent kinase inhibitor that is elevated in quiescent VSMCs and inhibits the G 1 to S phase transition and cell migration. (mdpi.com)
  • To determine whether embelin inhibits cell senescence in H 2 O 2 -induced senescence model of HDFs, the SA-β-galactosidase assay was performed. (springer.com)
  • Encodes a member of a plant specific family of cyclin dependent kinases. (nih.gov)
  • Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A expression and increased replication of primary human fibroblasts, as intended. (jci.org)
  • Expression of phosphorylated (p-)tyrosine, p-Akt, phosphorylated extracellular signal-regulated kinase (p-ERK) 1/ERK2 (p42/p44), and p27 after treatment of erlotinib was not associated with erlotinib sensitivity. (aacrjournals.org)
  • At least some cyclins contain a hydrophobic patch which may directly interact with substrates, conferring target specificity. (wikipedia.org)
  • Moreover, the expression of p21 and MMP1 genes were reduced by embelin in H 2 O 2 -treated HDFs in a dose-dependent manner. (springer.com)
  • However, COL1A1 genes were increased by embelin in H 2 O 2 -treated HDFs in a dose-dependent manner. (springer.com)
  • Recent genetic studies indicate that mutations of Cdkl family kinases are associated with neurodevelopmental and neuropsychiatric disorders in humans. (frontiersin.org)
  • In humans, mutations in FOXP3 results in an autoimmune syndrome termed IPEX (immunodysregulation, polyendocrinopathy enteropathy, X-linked syndrome), an X-linked immunodeficiency syndrome characterized by insulin-dependent diabetes, thyroiditis, massive T-cell infiltration in multiple organs and chronic wasting ( 6 - 8 ). (frontiersin.org)
  • Below each tab is a list of currently available Kinase Enzyme Systems (or those coming soon). (promega.com)
  • Click on any enzyme for additional information (such as Applications Note, the Catalog Page, or the NCBI Database entry) for that kinase. (promega.com)
  • Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor-positive (ER + ) breast cancer. (elsevier.com)
  • Thus the role of mammalian ERK1/2 kinases as regulators of cell proliferation is not a generic, but a highly specialized function. (wikipedia.org)
  • A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. (nih.gov)
  • In the case of classical MAP kinases, the activation loop contains a characteristic TxY (threonine-x-tyrosine) motif (TEY in mammalian ERK1 and ERK2 , TDY in ERK5 , TPY in JNKs , TGY in p38 kinases ) that needs to be phosphorylated on both the threonine and the tyrosine residues in order to lock the kinase domain in a catalytically competent conformation. (wikipedia.org)
  • Cyclin-dependent kinase 5-mediated hyperphosphorylation of sirtuin-1 contributes to the development of endothelial senescence and atherosclerosis. (springer.com)
  • Bai B, Vanhoutte PM, Wang Y. Loss-of-SIRT1 function during vascular ageing: hyperphosphorylation mediated by cyclin-dependent kinase 5. (springer.com)
  • In comparison to the three-tiered classical MAPK pathways, some atypical MAP kinases appear to have a more ancient, two-tiered system. (wikipedia.org)
  • Binding mode of the 4-anilinoquinazoline class of protein kinase inhibitor: X-ray crystallographic studies of 4-anilinoquinazolines bound to cyclin-dependent kinase 2 and p38 kinase. (expasy.org)
  • The crystal structure of the FKH domain bound to DNA has been solved and has been described as a "winged-helix" similar to the shape of a butterfly ( 2 ). (frontiersin.org)
  • This destruction of M cyclins leads to the final events of mitosis (e.g., spindle disassembly, mitotic exit). (wikipedia.org)
  • There are two main groups of cyclins, G1/S cyclins, which are essential for the control of the cell cycle at the G1/S (start) transition, and G2/M cyclins, which are essential for the control of the cell cycle at the G2/M (mitosis) transition. (embl.de)
  • These findings suggest that Cdkl2 is involved in cognitive function and provide in vivo evidence for the function of Cdkl family kinases expressed in terminally differentiated neurons in mice. (frontiersin.org)
  • The transcription factor myocyte enhancer factor 2 (MEF2) plays a critical role in neuronal survival. (jneurosci.org)