Cyclin-Dependent Kinases
Cyclin-Dependent Kinase 2
Cyclin D1
Cyclin A
Cyclin E
Cyclins
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase Inhibitor p27
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.
CDC2-CDC28 Kinases
Cell Cycle
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase 5
Cell Cycle Proteins
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.
Cyclin B
Cyclin C
Protein-Serine-Threonine Kinases
CDC2 Protein Kinase
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.
Cyclin D
G1 Phase
Cyclin-Dependent Kinase Inhibitor p16
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.
Cyclin-Dependent Kinase Inhibitor Proteins
Cyclin D3
Cyclin B1
Retinoblastoma Protein
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.
Phosphorylation
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinase Inhibitor p57
Tumor Suppressor Proteins
S Phase
Cyclin D2
Cyclin A1
Microtubule-Associated Proteins
Protein Kinases
Purines
Cell Division
Apoptosis
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.
Proto-Oncogene Proteins
E2F1 Transcription Factor
Cyclin A2
Phosphatidylinositol 3-Kinases
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.
Cyclin G
Tumor Cells, Cultured
Tumor Suppressor Protein p53
Mitosis
Cyclin G1
MAP Kinase Signaling System
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.
Transcription Factor DP1
Signal Transduction
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, Cultured
Blotting, Western
Enzyme Inhibitors
G2 Phase
E2F Transcription Factors
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.
Transfection
Calcium-Calmodulin-Dependent Protein Kinases
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)
Mutation
Proliferating Cell Nuclear Antigen
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.
Molecular Sequence Data
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.
DNA-Binding Proteins
Carrier Proteins
Nuclear Proteins
Base Sequence
RNA, Messenger
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.
Protein Kinase C
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.
Transcription Factors
src-Family Kinases
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.
Immunohistochemistry
Reverse Transcriptase Polymerase Chain Reaction
DNA Damage
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.
Amino Acid Sequence
p38 Mitogen-Activated Protein Kinases
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.
Cyclic AMP-Dependent Protein Kinases
Cyclin B2
Mitogen-Activated Protein Kinase 1
Protein Binding
Enzyme Activation
Gene Expression Regulation
Transcription, Genetic
Cyclin T
Mitogen-Activated Protein Kinase Kinases
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.
p21-Activated Kinases
Mitogen-Activated Protein Kinase 3
JNK Mitogen-Activated Protein Kinases
Protein-Tyrosine Kinases
Cyclin H
Cyclin G2
Calcium-Calmodulin-Dependent Protein Kinase Type 2
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.
MAP Kinase Kinase Kinases
Recombinant Fusion Proteins
3T3 Cells
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.
Creatine Kinase
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.
Models, Biological
Calcium
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.
Casein Kinase II
eIF-2 Kinase
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.
Intracellular Signaling Peptides and Proteins
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.
Binding Sites
Cell Nucleus
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)
Ribosomal Protein S6 Kinases
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.
Mitogen-Activated Protein 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).
MAP Kinase Kinase 1
Down-Regulation
Extracellular Signal-Regulated MAP Kinases
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.
Casein Kinases
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.
Serine
Pyruvate Kinase
Glycogen Synthase Kinase 3
RNA, Small Interfering
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.
Promoter Regions, Genetic
Receptor Protein-Tyrosine Kinases
Mice, Knockout
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.
Thymidine Kinase
MAP Kinase Kinase 4
Saccharomyces cerevisiae Proteins
Isoenzymes
Phosphotransferases (Alcohol Group Acceptor)
I-kappa B Kinase
Proto-Oncogene Proteins c-akt
E2F4 Transcription Factor
Protein Structure, Tertiary
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.
DNA Primers
1-Phosphatidylinositol 4-Kinase
Aurora Kinases
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.
rho-Associated Kinases
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.
Protein Kinase C-alpha
HeLa Cells
S Phase Cell Cycle Checkpoints
Protein Kinase C-delta
Saccharomyces cerevisiae
Rats, Sprague-Dawley
Substrate Specificity
Gene Expression Regulation, Neoplastic
Proteins
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.
Oncogene Proteins
Transcriptional Activation
AMP-Activated Protein Kinases
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.
Immunoblotting
Cyclin I
Flow Cytometry
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.
Tyrosine
Dose-Response Relationship, Drug
Sequence Homology, Amino Acid
Diacylglycerol Kinase
Precipitin Tests
Retinoblastoma-Binding Protein 1
Focal Adhesion Kinase 1
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.
Neoplasm Proteins
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.
Fibroblasts
Janus Kinase 2
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.
Tetradecanoylphorbol Acetate
Myosin-Light-Chain Kinase
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.
Focal Adhesion Protein-Tyrosine Kinases
Ribosomal Protein S6 Kinases, 90-kDa
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.
TOR Serine-Threonine Kinases
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.
Neurons
Threonine
Gene Expression
Cloning, Molecular
Protein Kinase C-epsilon
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.
Cyclic AMP
MAP Kinase Kinase 2
Androstadienes
MAP Kinase Kinase Kinase 1
Cell Survival
Up-Regulation
Genes, bcl-1
Protein Kinase C beta
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.
Gene Expression Regulation, Enzymologic
Cell Differentiation
Cyclic GMP-Dependent Protein Kinases
RNA Interference
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.
Protein Transport
Membrane Proteins
DNA
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).
Adenosine Triphosphate
Adaptor Proteins, Signal Transducing
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
Phosphoprotein Phosphatases
Trans-Activators
Cell Membrane
Genes, p16
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.
Mitogen-Activated Protein Kinase 8
Mutagenesis, Site-Directed
Phosphoglycerate Kinase
Casein Kinase I
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.
NF-kappa B
MAP Kinase Kinase 6
Tat activates human immunodeficiency virus type 1 transcriptional elongation independent of TFIIH kinase. (1/252)
Tat stimulates human immunodeficiency virus type 1 (HIV-1) transcriptional elongation by recruitment of the human transcription elongation factor P-TEFb, consisting of Cdk9 and cyclin T1, to the HIV-1 promoter via cooperative binding to the nascent HIV-1 transactivation response RNA element. The Cdk9 kinase activity has been shown to be essential for P-TEFb to hyperphosphorylate the carboxy-terminal domain (CTD) of RNA polymerase II and mediate Tat transactivation. Recent reports have shown that Tat can also interact with the multisubunit transcription factor TFIIH complex and increase the phosphorylation of CTD by the Cdk-activating kinase (CAK) complex associated with the core TFIIH. These observations have led to the proposal that TFIIH and P-TEFb may act sequentially and in a concerted manner to promote phosphorylation of CTD and increase polymerase processivity. Here, we show that under conditions in which a specific and efficient interaction between Tat and P-TEFb is observed, only a weak interaction between Tat and TFIIH that is independent of critical amino acid residues in the Tat transactivation domain can be detected. Furthermore, immunodepletion of CAK under high-salt conditions, which allow CAK to be dissociated from core-TFIIH, has no effect on either basal HIV-1 transcription or Tat activation of polymerase elongation in vitro. Therefore, unlike the P-TEFb kinase activity that is essential for Tat activation of HIV-1 transcriptional elongation, the CAK kinase associated with TFIIH appears to be dispensable for Tat function. (+info)The transcriptional inhibitors, actinomycin D and alpha-amanitin, activate the HIV-1 promoter and favor phosphorylation of the RNA polymerase II C-terminal domain. (2/252)
Actinomycin D and alpha-amanitin are commonly used to inhibit transcription. Unexpectedly, however, the transcription of the human immunodeficiency virus (HIV-1) long terminal repeats (LTR) is shown to be activated at the level of elongation, in human and murine cells exposed to these drugs, whereas the Rous sarcoma virus LTR, the human cytomegalovirus immediate early gene (CMV), and the HSP70 promoters are repressed. Activation of the HIV LTR is independent of the NFkappaB and TAR sequences and coincides with an enhanced average phosphorylation of the C-terminal domain (CTD) from the largest subunit of RNA polymerase II. Both the HIV-1 LTR activation and the bulk CTD phosphorylation enhancement are prevented by several CTD kinase inhibitors, including 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole. The efficacies of the various compounds to block CTD phosphorylation and transcription in vivo correlate with their capacities to inhibit the CDK9/PITALRE kinase in vitro. Hence, the positive transcription elongation factor, P-TEFb, is likely to contribute to the average CTD phosphorylation in vivo and to the activation of the HIV-1 LTR induced by actinomycin D. (+info)Human and rodent transcription elongation factor P-TEFb: interactions with human immunodeficiency virus type 1 tat and carboxy-terminal domain substrate. (3/252)
The human immunodeficiency virus type 1 transcriptional regulator Tat increases the efficiency of elongation, and complexes containing the cellular kinase CDK9 have been implicated in this process. CDK9 is part of the Tat-associated kinase TAK and of the elongation factor P-TEFb (positive transcription elongation factor-b), which consists minimally of CDK9 and cyclin T. TAK and P-TEFb are both able to phosphorylate the carboxy-terminal domain (CTD) of RNA polymerase II, but their relationships to one another and to the stimulation of elongation by Tat are not well characterized. Here we demonstrate that human cyclin T1 (but not cyclin T2) interacts with the activation domain of Tat and is a component of TAK as well as of P-TEFb. Rodent (mouse and Chinese hamster) cyclin T1 is defective in Tat binding and transactivation, but hamster CDK9 interacts with human cyclin T1 to give active TAK in hybrid cells containing human chromosome 12. Although TAK is phosphorylated on both serine and threonine residues, it specifically phosphorylates serine 5 in the CTD heptamer. TAK is found in the nuclear and cytoplasmic fractions of human cells as a large complex (approximately 950 kDa). Magnesium or zinc ions are required for the association of Tat with the kinase. We suggest a model in which Tat first interacts with P-TEFb to form the TAK complex that engages with TAR RNA and the elongating transcription complex, resulting in hyperphosphorylation of the CTD on serine 5 residues. (+info)Transcriptional regulation by targeted recruitment of cyclin-dependent CDK9 kinase in vivo. (4/252)
The CDK9 kinase in association with Cyclin T is a component of the transcription positive-acting complex pTEFb which facilitates the transition from abortive to productive transcription elongation by phosphorylating the carboxyl-terminal domain of RNA polymerase II. The Cyclin T1/CDK9 complex is implicated in Tat transactivation, and it has been suggested that Tat functions by recruiting this complex to RNAPII through cooperative binding to RNA. Here, we demonstrate that targeted recruitment of Cyclin T1/CDK9 kinase complex to specific promoters, through fusion to a DNA-binding domain of either Cyclin T1 or CDK9 kinase, stimulates transcription in vivo. Transcriptional enhancement was dependent on active CDK9, as a catalytically inactive form had no transcriptional effect. We determined that, unlike conventional activators, DNA-bound CDK9 does not activate enhancerless TATA-promoters unless TBP is overexpressed, suggesting that CDK9 acts in vivo at a step subsequent to TFIID recruitment DNA-bound. Finally, we determined that CDK9-mediated transcriptional activation is mediated by preferentially stimulating productive transcription elongation. (+info)B cell antigen receptor-mediated activation of cyclin-dependent retinoblastoma protein kinases and inhibition by co-cross-linking with Fc gamma receptors. (5/252)
Cross-linking the B cell Ag receptor (BCR) to surface Fc receptors for IgG (Fc gamma R) inhibits G1-to-S progression; the mechanism by which this occurs is not completely known. We investigated the regulation of three key cell cycle regulatory components by BCR-Fc gamma R co-cross-linking: G1-cyclins, cyclin-dependent kinases (Cdks), and the retinoblastoma gene product (Rb). Rb functions to suppress G1-to-S progression in mammalian cells. Rb undergoes cell-cycle-dependent phosphorylation, leading to its inactivation and thereby promoting S phase entry. We demonstrate in this paper for the first time that BCR-induced Rb phosphorylation is abrogated by co-cross-linking with Fc gamma R. The activation of Cdk4/6- and Cdk2-dependent Rb protein kinases is concomitantly blocked. Fc gamma R-mediated inhibition of Cdk2 activity results in part from an apparent failure to express Cdk2 protein. By contrast, inhibition of Cdk4/6 activities is not due to suppression of Cdk4/6 or cyclins D2/D3 expression or inhibition of Cdk-activating kinase activity. Cdk4- and Cdk6-immune complexes recovered from B cells following BCR-Fc gamma R co-cross-linking are devoid of coprecipitated D-type cyclins, indicating that inhibition of their Rb protein kinase activities is due in part to the absence of bound D-type cyclin. Thus, BCR-derived activation signals that up-regulate D-type cyclin and Cdk4/6 protein expression remain intact; however, Fc gamma R-mediated signals block cyclin D-Cdk4/6 assembly or stabilization. These results suggest that assembly or stabilization of D-type cyclin holoenzyme complexes 1) is an important step in the activation of Cdk4/6 by BCR signals, and 2) suffice in providing a mechanism to account for inhibition of BCR-stimulated Rb protein phosphorylation by Fc gamma R. (+info)Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription. (6/252)
Important progress in the understanding of elongation control by RNA polymerase II (RNAPII) has come from the recent identification of the positive transcription elongation factor b (P-TEFb) and the demonstration that this factor is a protein kinase that phosphorylates the carboxyl-terminal domain (CTD) of the RNAPII largest subunit. The P-TEFb complex isolated from mammalian cells contains a catalytic subunit (CDK9), a cyclin subunit (cyclin T1 or cyclin T2), and additional, yet unidentified, polypeptides of unknown function. To identify additional factors involved in P-TEFb function we performed a yeast two-hybrid screen using CDK9 as bait and found that cyclin K interacts with CDK9 in vivo. Biochemical analyses indicate that cyclin K functions as a regulatory subunit of CDK9. The CDK9-cyclin K complex phosphorylated the CTD of RNAPII and functionally substituted for P-TEFb comprised of CDK9 and cyclin T in in vitro transcription reactions. (+info)Requirement for a kinase-specific chaperone pathway in the production of a Cdk9/cyclin T1 heterodimer responsible for P-TEFb-mediated tat stimulation of HIV-1 transcription. (7/252)
Tat activation of HIV-1 transcription is mediated by human transcription elongation factor P-TEFb, which interacts with Tat and phosphorylates the C-terminal domain of RNA polymerase II. The catalytic subunit of the P-TEFb complex, Cdk9, has been shown to interact with cyclin T and several other proteins of unknown identity. Consequently, the exact subunit composition of active P-TEFb has not been determined. Here we report the affinity purification and identification of the Cdk9-associated proteins. In addition to forming a heterodimer with cyclin T1, Cdk9 interacted with the molecular chaperone Hsp70 or a kinase-specific chaperone complex, Hsp90/Cdc37, to form two separate chaperone-Cdk9 complexes. Although the Cdk9/cyclin T1 dimer was exceptionally stable and produced slowly in the cell, free and unprotected Cdk9 appeared to be degraded rapidly. Several lines of evidence indicate the heterodimer of Cdk9/cyclin T1 to be the mature, active form of P-TEFb responsible for phosphorylation of the C-terminal domain of RNA polymerase II interaction with the Tat activation domain, and mediation of Tat activation of HIV-1 transcription. Pharmacological inactivation of Hsp90/Cdc37 function by geldanamycin revealed an essential role for the chaperone-Cdk9 complexes in generation of Cdk9/cyclin T1. Our data suggest a previously unrecognized chaperone-dependent pathway involving the sequential actions of Hsp70 and Hsp90/Cdc37 in the stabilization/folding of Cdk9 as well as the assembly of an active Cdk9/cyclin T1 complex responsible for P-TEFb-mediated Tat transactivation. (+info)Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation. (8/252)
B-Myb is a transcription factor belonging to the myb family, whose activity has been associated with augmented DNA synthesis and cell cycle progression. We showed recently that B-Myb autoregulates its own expression through promoter transactivation. We report in this study that CDK9, the cyclin T associated kinase, which phosphorylates and activates RNA-Polymerase II, suppresses B-Myb autoregulation through direct interaction with the carboxyl-terminus of the B-Myb protein. Down-regulation of the transactivating ability of B-Myb is independent of the kinase activity of CDK9, because a kinase deficient mutant (dn-CDK9) also represses B-myb gene autoregulation. Overexpression of CDK9 did not result in suppression of p53-dependent transactivation or inhibition of the basal activity of the promoters tested so far, demonstrating that CDK9 is a B-Myb-specific repressor. Rather, transfection of the dominant negative dn-CDK9 construct inhibited the basal activity of the reporter genes, confirming an essential role for CDK9 in gene transcription. In addition, Cyclin T1 restores B-Myb transactivating activity when co-transfected along with CDK9, suggesting that the down-regulatory effect observed on B-Myb is specifically due to CDK9 alone. Thus, our data suggest that CDK9 is involved in the negative regulation of activated transcription mediated by certain transcription factors, such as B-Myb. This may indicate the existence of a feedback loop, mediated by the different activities of CDK9, which links basal with activated transcription. (+info)
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Cyclin-dependent kinase 4
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 ...
Zotiraciclib
... a Potent Inhibitor of Cyclin Dependent Kinases (CDKs), Janus Kinase 2 (JAK2), and Fms-like Tyrosine Kinase-3 (FLT3) for the ... It crosses the blood brain barrier and acts by depleting Myc through the inhibition of cyclin-dependent kinase 9 (CDK9). It is ... Blachly JS, Byrd JC, Grever M (April 2016). "Cyclin-dependent kinase inhibitors for the treatment of chronic lymphocytic ... Discovery of Kinase Spectrum Selective Macrocycle (16E)-14-Methyl-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)] ...
RELA
... is required for activation of a subset of NF-kappaB-dependent genes by recruiting cyclin-dependent kinase 9/cyclin T1 complexes ... TANK-binding kinase-1 (TBK1) and TRAF2-associated kinase (T2K)). The fact that RELA can be modified by a collection of kinases ... including glycogen-synthase kinase-3β (GSK3β), AKT/phosphatidylinositol 3-kinase (PI3K) and NF-κB activating kinase (NAK, i.e. ... ribosomal subunit kinase-1 (RSK1) also has the ability to phosphorylate RELA at serine 536 in a p53-dependent manner. A couple ...
Epstein-Barr virus nuclear antigen 2
Regulation of transcription initiation and elongation by EBNA 2 is done part through cyclin-dependent kinase 9 (CDK9) dependent ... 71 (9): 6611-8. PMC 191939. PMID 9261383. Zimber-Strobl U, Kremmer E, Grässer F, Marschall G, Laux G, Bornkamm GW (January 1993 ... 70 (9): 6020-8. PMC 190622. PMID 8709224. Palermo RD, Webb HM, Gunnell A, West MJ (August 2008). "Regulation of transcription ...
CDKN2A
p16 inhibits cyclin dependent kinases 4 and 6 (CDK4 and CDK6) and thereby activates the retinoblastoma (Rb) family of proteins ... "CDKN2A cyclin dependent kinase inhibitor 2A [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-10-11. ... CDKN2A, also known as cyclin-dependent kinase inhibitor 2A, is a gene which in humans is located at chromosome 9, band p21.3. ... "CDKN2A - Cyclin-dependent kinase inhibitor 2A - Homo sapiens (Human) - CDKN2A gene & protein". www.uniprot.org. Retrieved 2016- ...
Dinaciclib
... 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 ...
List of MeSH codes (D12.776.930)
... cyclin-dependent kinase 9 MeSH D12.776.930.977.249.500 - hepatocyte nuclear factor 3-alpha MeSH D12.776.930.977.249.750 - ...
Anthony Barrett
... pyrimidine Is a Potent Inhibitor of Cyclin-Dependent Protein Kinases 1, 2, and 9, Which Demonstrates Antitumor Effects in Human ... "The Development of a Selective Cyclin-Dependent Kinase Inhibitor That Shows Antitumor Activity". Cancer Research. 69 (15): 6208 ... unmet medical need with the invention of highly selective and bioavailable inhibitors of the Cyclin Dependent Kinases including ... Miyatake-Ondozabal, Hideki; Barrett, Anthony G. M. (3 December 2010). "Total Synthesis of TAK-Kinase Inhibitor LL-Z1640-2 via ...
Cyclin K
These cyclins may regulate transcription through their association with and activation of cyclin-dependent kinases (CDKs) ... "Crystal structure of human cyclin K, a positive regulator of cyclin-dependent kinase 9". Journal of Molecular Biology. 366 (2 ... "Cyclin K inhibits HIV-1 gene expression and replication by interfering with cyclin-dependent kinase 9 (CDK9)-cyclin T1 ... a positive regulator of cyclin-dependent kinase 9". Journal of Molecular Biology. 366 (2): 563-73. doi:10.1016/j.jmb.2006.11. ...
p21, wolna encyklopedia
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 ...
Cyclin-dependent kinase
CDK6; cyclin D1, cyclin D2, cyclin D3 CDK7; cyclin H CDK8; cyclin C CDK9; cyclin T1, cyclin T2a, cyclin T2b, cyclin K CDK10 ... cyclin A, cyclin B CDK2; cyclin A, cyclin E CDK3; cyclin C CDK4; cyclin D1, cyclin D2, cyclin D3 CDK5; CDK5R1, CDK5R2. See also ... A cyclin-dependent kinase inhibitor (CKI) is a protein that interacts with a cyclin-CDK complex to block kinase activity, ... Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell ...
List of MeSH codes (D12.776)
... cyclin-dependent kinase inhibitor p27 MeSH D12.776.624.776.355.700 - cyclin-dependent kinase inhibitor p57 See List of MeSH ... cyclin-dependent kinase 5 MeSH D12.776.167.200.067.900 - cyclin-dependent kinase 9 MeSH D12.776.167.200.580.500 - cdc2 protein ... cyclin-dependent kinase inhibitor p15 MeSH D12.776.624.776.355.200 - cyclin-dependent kinase inhibitor p16 MeSH D12.776.624.776 ... cyclin-dependent kinase inhibitor p18 MeSH D12.776.624.776.355.400 - cyclin-dependent kinase inhibitor p19 MeSH D12.776.624.776 ...
CDKL5
... is a gene that provides instructions for making a protein called cyclin-dependent kinase-like 5 also known as serine/ ... "Preclinical Program for Cyclin-Dependent Kinase-Like 5 (CDKL5) Deficiency". Amicus Therapeutics Press Release. 6 July 2016. ... G40.42 Cyclin-dependent kinase Rett syndrome West syndrome GRCh38: Ensembl release 89: ENSG00000008086 - Ensembl, May 2017 ... The CDKL5 protein acts as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of ...
Cyclin-dependent kinase 1
... like other cyclin-dependent kinases, contains a T-loop, which, in the absence of an interacting cyclin, prevents substrate ... Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that ... De Bondt HL, Rosenblatt J, Jancarik J, Jones HD, Morgan DO, Kim SH (June 1993). "Crystal structure of cyclin-dependent kinase 2 ... Overview of all the structural information available in the PDB for UniProt: P06493 (Cyclin-dependent kinase 1) at the PDBe-KB. ...
Cyclin-dependent kinase 10
"Entrez Gene: CDK10 cyclin-dependent kinase (CDC2-like) 10". Kasten M, Giordano A (Apr 2001). "Cdk10, a Cdc2-related kinase, ... Cyclin-dependent kinase 10 has been shown to interact with ETS2. GRCh38: Ensembl release 89: ENSG00000185324 - Ensembl, May ... This kinase has been shown to play a role in cellular proliferation. Its function is limited to cell cycle G2-M phase. At least ... Cell division protein kinase 10 is an enzyme that in humans is encoded by the CDK10 gene. The protein encoded by this gene ...
Cyclin-dependent kinase 6
Cyclin D1, Cyclin D3, P16, PPM1B, and PPP2CA. Cell cycle Cyclin-dependent kinase Cyclin-dependent kinase 4 Mitosis The ... 2003). "Expression of Cyclin-Dependent Kinase 6, but Not Cyclin-Dependent Kinase 4, Alters Morphology of Cultured Mouse ... "Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein ...
Cyclin-dependent kinase 2
... has been shown to interact with: BRCA1, CDK2AP1, CDKN1B CDKN3, CEBPA, Cyclin A1, Cyclin E1, Flap ... CDK2 cyclin-dependent kinase 2". Echalier A, Endicott JA, Noble ME (March 2010). "Recent developments in cyclin-dependent ... Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the ... The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein kinases. This protein ...
Cyclin-dependent kinase 7
"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... Cyclin-dependent kinase 7, or cell division protein kinase 7, is an enzyme that in humans is encoded by the CDK7 gene. The ... Cyclin-dependent kinase 7 has been shown to interact with: Androgen receptor, Cyclin H, GTF2H1, MNAT1, P53, SUPT5H, and XPB. ... "Entrez Gene: CDK7 cyclin-dependent kinase 7 (MO15 homolog, Xenopus laevis, cdk-activating kinase)". Patel H, Abduljabbar R, Lai ...
Cyclin-dependent kinase complex
... cyclin-dependent kinase (CDK), with a regulatory subunit, cyclin. Once cyclin-dependent kinases bind to cyclin, the formed ... Cyclin Cyclin-dependent kinase Malumbres M, Barbacid M. Mammalian cyclin-dependent kinases. Trends Biochem. Sci. 2005 Nov;30(11 ... A cyclin-dependent kinase complex (CDKC, cyclin-CDK) is a protein complex formed by the association of an inactive catalytic ... As previously mentioned, in yeast, only one cyclin-dependent kinase (CDK) is associated with several different cyclins. However ...
Cyclin-dependent kinase 4
"Entrez Gene: CDK4 cyclin-dependent kinase 4". "CDK4 - Cyclin-dependent kinase 4 - Homo sapiens (Human) - CDK4 gene & protein". ... 1995). "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. ... "The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner". ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ...
Cyclin-dependent kinase 9
... or CDK9 is a cyclin-dependent kinase associated with P-TEFb. The protein encoded by this gene is a ... "Entrez Gene: CDK9 cyclin-dependent kinase 9 (CDC2-related kinase)". MacLachlan TK, Sang N, De Luca A, Puri PL, Levrero M, ... Cyclin-Dependent+Kinase+9 at the US National Library of Medicine Medical Subject Headings (MeSH) Drosophila Cyclin dependent ... member of the cyclin-dependent kinase (CDK) family. CDK family members are highly similar to the gene products of S. cerevisiae ...
Cyclin-dependent kinase 3
"Entrez Gene: CDK3 cyclin-dependent kinase 3". Bullrich F, MacLachlan TK, Sang N, et al. (1995). "Chromosomal mapping of members ... 2002). "ik3-1/Cables is a substrate for cyclin-dependent kinase 3 (cdk 3)". Eur. J. Biochem. 268 (23): 6076-82. doi:10.1046/j. ... Meikrantz W, Schlegel R (1996). "Suppression of apoptosis by dominant negative mutants of cyclin-dependent protein kinases". J ... Ren S, Rollins BJ (2004). "Cyclin C/cdk3 promotes Rb-dependent G0 exit". Cell. 117 (2): 239-51. doi:10.1016/S0092-8674(04)00300 ...
Cyclin-dependent kinase 8
"Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proceedings of the National ... The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate ... "Entrez Gene: CDK8 cyclin-dependent kinase 8". Nemet J, Jelicic B, Rubelj I, Sopta M (Feb 2014). "The two faces of Cdk8, a ... Cyclin-dependent kinase 8 has been shown to interact with: CCNC CREB binding protein CRSP3 MED1 MED12 MED14 MED16 MED17 MED21 ...
Centrosome cycle
... by cyclin-dependent kinase 2-cyclin E and its role in centrosome duplication". The Journal of Biological Chemistry. 276 (24): ... "CDK2 cyclin dependent kinase 2 [Homo sapiens (human)]". Gene - NCBI. Retrieved 1 December 2019. Hinchcliffe EH, Li C, Thompson ... This link between the cell cycle and the centrosome cycle is mediated by cyclin-dependent kinase 2 (Cdk2). Cdk2 is a protein ... Matsumoto Y, Hayashi K, Nishida E (April 1999). "Cyclin-dependent kinase 2 (Cdk2) is required for centrosome duplication in ...
Cyclin-dependent kinase inhibitor 1C
... is a tight-binding inhibitor of several G1 cyclin/Cdk complexes and a negative regulator ... Cyclin-dependent kinase inhibitor 1C (p57, Kip2), also known as CDKN1C, is a protein which in humans is encoded by the CDKN1C ... "Entrez Gene: CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2)". Matsuoka S, Edwards MC, Bai C, Parker S, Zhang P, ... Cyclin-dependent kinase inhibitor 1C has been shown to interact with: LIMK1, MYBL2, MyoD, and PCNA. ENSG00000129757 GRCh38: ...
STX1A
"Regulation of Munc-18/syntaxin 1A interaction by cyclin-dependent kinase 5 in nerve endings". The Journal of Biological ... Syntaxins bind synaptotagmin in a calcium-dependent fashion and interact with voltage dependent calcium and potassium channels ... Li C, Ullrich B, Zhang JZ, Anderson RG, Brose N, Südhof TC (June 1995). "Ca(2+)-dependent and -independent activities of neural ... Beckman ML, Bernstein EM, Quick MW (August 1998). "Protein kinase C regulates the interaction between a GABA transporter and ...
TSC1
... by cyclin-dependent kinase 1/cyclin B". The Journal of Biological Chemistry. 278 (51): 51372-9. doi:10.1074/jbc.M303956200. ... "Hamartin and tuberin interaction with the G2/M cyclin-dependent kinase CDK1 and its regulatory cyclins A and B". Journal of ... Tsc1 functions as a facilitator of Hsp90 in chaperoning the kinase and non-kinase clients including Tsc2, therefore preventing ... interacts with polo-like kinase 1 in a phosphorylation-dependent manner". Human Molecular Genetics. 15 (2): 287-97. doi:10.1093 ...
Seliciclib
De Azevedo WF, Leclerc S, Meijer L, Havlicek L, Strnad M, Kim SH (1997). "Inhibition of cyclin-dependent kinases by purine ... Doree M, Galas S (1994). "The cyclin-dependent protein kinases and the control of cell division". FASEB J. 8 (14): 1114-1121. ... Seliciclib (roscovitine or CYC202) is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase ( ... Schang LM, Rosenberg A, Schaffer PA (2000). "Roscovitine, a specific inhibitor of cellular cyclin-dependent kinases, inhibits ...
SERTAD1
"The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner". ... "The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner". ... SERTAD1 has been shown to interact with: CREB-binding protein, Cyclin-dependent kinase 4, and P16. GRCh38: Ensembl release 89: ... 43 (14): 4394-9. doi:10.1021/bi035601s. PMID 15065884. Li J, Muscarella P, Joo SH, Knobloch TJ, Melvin WS, Weghorst CM, Tsai MD ...
Histone
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.[ ...
Cyclin T2
Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which ... Simone C, Giordano A (2007). "Abrogation of signal-dependent activation of the cdk9/cyclin T2a complex in human RD ... This cyclin and its kinase partner CDK9 were found to be subunits of the transcription elongation factor p-TEFb. The p-TEFb ... "MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner". Mol. Cell. Biol. 23 (14): 4859-69 ...
Cell biology
The cell cycle is regulated by a series of signalling factors and complexes such as cyclin-dependent kinases and p53, to name a ... ISBN 978-1-4292-3413-9.. *^ "The Size, Shape, And Arrangement of Bacterial Cells". classes.midlandstech.edu. Archived from the ... Other factors such as size, the way in which they reproduce, and the number of cells distinguish them from one another.[9] ... original on 9 August 2016. Retrieved 22 November 2015.. *^ a b Hardin, Jeff. Becker's World of the Cell. ISBN 978-0-321-71602-6 ...
Proteasome
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 ... 268 (5210): 533-9. doi:10.1126/science.7725097. PMID 7725097.. *^ a b c d e f g h i j Dong Y, Zhang S, Wu Z, Li X, Wang WL, Zhu ...
Aminoacyl tRNA synthetase
"Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational ... 11 (9): 668-74. doi:10.1038/nrm2956. PMC 3042954. PMID 20700144.. *^ Lee SW, Cho BH, Park SG, Kim S (August 2004). "Aminoacyl- ... 9 (3): 145-53. doi:10.1038/nchembio.1158. PMID 23416400.. *^ Vona B, Maroofian R, Bellacchio E, Najafi M, Thompson K, Alahmad A ... 3 (9): 954-60. PMID 9292495.. *^ Kaiser F, Bittrich S, Salentin S, Leberecht C, Haupt VJ, Krautwurst S, Schroeder M, Labudde D ...
p21
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 ...
Linalol, wolna encyklopedia
... preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase ... Używany też jako insektycyd[9]. Jest badany jako potencjalny lek w terapii białaczki, raka szyjki macicy i innych chorób ... InChI=1S/C10H18O/c1-5-10(4,11)8-6-7-9(2)3/h5,7,11H,1,6,8H2,2-4H3 ...
Mitosis
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 ...
NMDA receptor
"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 ...
Intracranial aneurysm
... endothelin receptor A and cyclin dependent kinase inhibitor. Mutations in interleukin 6 may be protective.[citation needed]. ... 355 (9): 928-39. doi:10.1056/nejmra052760. PMID 16943405.. *^ a b c d e f Goljan, Edward F. (2006). Rapid Review Pathology (2nd ... 33 (9): 1249-1252. doi:10.1016/j.ajem.2015.05.012.. *^ Raja, PV; Huang, J; Germanwala, AV; Gailloud, P; Murphy, KP; Tamargo, RJ ... ISBN 0-07-159379-9.. *^ Caranci, F.; Briganti, F.; Cirillo, L.; Leonardi, M.; Muto, M. (2012). "Epidemiology and genetics of ...
ডিএনএ অনুলিপন - উইকিপিডিয়া
"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: ...
Tat (HIV)
... 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] ...
Hsp70
"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 ... Hsp70 inhibits this process by blocking the recruitment of procaspase-9 to the Apaf-1/dATP/cytochrome c apoptosome complex. It ... This complex then cleaves procaspase-9, activating caspase-9 and eventually inducing apoptosis via caspase-3 activation. ...
CDH1 (gene)
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 ...
GNB1
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 ...
Apoptosis
Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bad (a Bcl-2 ... Caspases are proteins that are highly conserved, cysteine-dependent aspartate-specific proteases. There are two types of ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... the protein is cleaved by a calcium-dependent calpain protease ... "Apoptosis induced by Oropouche virus infection in HeLa cells is dependent on virus protein expression". Virus Research. 149 (1 ...
Transferase
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 ...
Splenic marginal zone lymphoma
November 1999). "Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q ... Mantle cell lymphoma is excluded due to the lack of CD5 and cyclin-D1 expression. Clonal rearrangements of the immunoglobulin ... July 1998). "Absence of cyclin D1 protein expression in splenic marginal zone lymphoma". Mod. Pathol. 11 (7): 601-6. PMID ... 75 (5): 741-9. doi:10.1016/0002-9343(83)90402-3. PMID 6638043. Franco V, Florena AM, Campesi G (December 1996). " ...
CDC42
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 ...
Ribociclib
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 ...
Factor de crecimiento transformante beta 1, la enciclopedia libre
... 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 ... de 2001). «Conserved role for 14-3-3epsilon downstream of type I TGFbeta receptors». FEBS Lett. (Netherlands) 490 (1-2): 65-9. ...
BRCA1
... 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 ...
Amphiphysin
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 ...
HIV bahasa Indonesia, ensiklopedia bebas
... phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase ... Curr Opin Infect Dis. 18, 9-15. PMID 15647694. *Dybul, M., Fauci, A. S., Bartlett, J. G., Kaplan, J. E., Pau, A. K., and the ... Bukrinsky M, Adzhubei A. (1999) Viral protein R of HIV-1. Rev Med Virol 9, 39-49 PMID 10371671 ... 81 AA (terfosforilasi), 9,2 & 16 kDalton. retikulum endoplasma, protein transmembran. Degradasi CD4; meningkatkan pelepasan HIV ...
G protein
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 ...
Cell growth
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. ...
Cleavage (embryo)
The process follows fertilization, with the transfer being triggered by the activation of a cyclin-dependent kinase complex.[1] ... high levels of proteins that control cell cycle progression such as the cyclins and their associated cyclin-dependent kinases ( ... cdk). The complex Cyclin B/CDK1 a.k.a. MPF (maturation promoting factor) promotes entry into mitosis. ... 97 (9): 4434-7. Bibcode:2000PNAS...97.4434S. doi:10.1073/pnas.97.9.4434. JSTOR 122407. PMC 34316 . PMID 10781038.. ...
Histone acetylation and deacetylation
... die during embryogenesis and showed a drastic reduction in the production but increased expression of Cyclin-Dependent Kinase ... Binding of HDACs to MEF2 inhibits muscle differentiation, which can be reversed by action of Ca2+/calmodulin-dependent kinase ( ... Nucleosome formation is dependent on the positive charges of the H4 histones and the negative charge on the surface of H2A ... The last is TAFII250 which has a Kinase domain at the N-terminus region, two bromodomains located at the C-terminus region and ...
Cyclin-dependent kinase 9 - Wikipedia
Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb. The protein encoded by this gene is a ... "Entrez Gene: CDK9 cyclin-dependent kinase 9 (CDC2-related kinase)". MacLachlan TK, Sang N, De Luca A, Puri PL, Levrero M, ... Cyclin-Dependent+Kinase+9 at the US National Library of Medicine Medical Subject Headings (MeSH) Drosophila Cyclin dependent ... member of the cyclin-dependent kinase (CDK) family. CDK family members are highly similar to the gene products of S. cerevisiae ...
RCSB PDB - Gene View
- CDK9 - cyclin dependent kinase 9
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Cyclin Dependent Kinase 9 - Pipeline Review, H2 2017
Summary Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division ... Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase ... is a cyclin-dependent kinase associated with P-TEFb. This kinase was found to be a component of the multiprotein complex TAK/P- ... Cyclin Dependent Kinase 9 - Pipeline Review, H2 2017. Wednesday, November 15, 2017 General News ...
Cdk9 - Cyclin-dependent kinase 9 - Mus musculus (Mouse) - Cdk9 gene & protein
Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P- ... The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in ... Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell ... Protein kinase involved in the regulation of transcription. ... Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) ...
cdk-9 - Probable cyclin-dependent kinase 9 - Caenorhabditis elegans - cdk-9 gene & protein
CDK9/cyclin-T) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the ... Essential member of the cyclin-dependent kinase pair ( ... Probable cyclin-dependent kinase 9 (EC:2.7.11.22, EC:2.7.11.23) ... cyclin-dependent protein serine/threonine kinase activity Source: GO_Central. *RNA polymerase II carboxy-terminal domain kinase ... Essential member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation ...
Cyclin-Dependent Kinase-9 | Circulation Research
Strikingly, RNA polymerase II (RNAPII) is itself a substrate for two protein kinases-the cyclin-dependent kinases Cdk7 and Cdk9 ... Cyclin-Dependent Kinase-9. An RNAPII Kinase at the Nexus of Cardiac Growth and Death Cascades. Motoaki Sano, Michael D. ... Cyclin-Dependent Kinase-9: An RNAPII Kinase at the Nexus of Cardiac Growth and Death Cascades Ryozo Nagai Guest Editor ... P-TEFb, a cyclin-dependent kinase controlling elongation by RNA polymerase II. Mol Cell Biol. 2000; 20: 2629-2634. ...
CSB-Dependent Cyclin-Dependent Kinase 9 Degradation and RNA Polymerase II Phosphorylation during Transcription-Coupled Repair. ...
... CSB-Dependent Cyclin-Dependent Kinase 9 Degradation and RNA Polymerase II Phosphorylation during Transcription-Coupled Repair ... CSB-Dependent Cyclin-Dependent Kinase 9 Degradation and RNA Polymerase II Phosphorylation during Transcription-Coupled Repair ... CSB-Dependent Cyclin-Dependent Kinase 9 Degradation and RNA Polymerase II Phosphorylation during Transcription-Coupled Repair ...
Cyclin-Dependent Kinase 9 (CDK9) Inhibitor -Pipeline Insight, 2018
Cyclin Dependent Kinase 4 (Cell Division Protein Kinase 4 or PSK J3 or CDK4 or EC 2.7.11.22) - Pipeline Review, H1 2018 * Drug ... Cyclin-Dependent Kinase 6 (Cell Division Protein Kinase 6 or EC 2.7.11.22) - Pipeline Review, H1 2016 * Drug Pipelines ... 6. Cyclin-Dependent Kinase 9 (CDK9) Inhibitor Pipeline Products in Non-clinical Stages 6.1 Drug Name : Company Name*Product ... 5. Cyclin-Dependent Kinase 9 (CDK9) Inhibitor Pipeline Products in Clinical Stages. 5.1 Drug Name : Company Name*Product ...
Deregulations in the Cyclin-Dependent Kinase-9-Related Pathway in Cancer: Implications for Drug Discovery and Development
... ... CDK9 is present in two isoforms termed CDK9-42 and CDK9-55 that bind noncovalently type T cyclins and cyclin K. This ... These studies may lead to the improvement of kinase inhibitors for the treatment of the previously mentioned pathological ... This review describes the CDK9-related pathway deregulations in malignancies and the development of kinase inhibitors in cancer ...
Cyclin-dependent kinase 9 | definition of cyclin-dependent kinase 9 by Medical dictionary
What is cyclin-dependent kinase 9? Meaning of cyclin-dependent kinase 9 medical term. What does cyclin-dependent kinase 9 mean? ... Looking for online definition of cyclin-dependent kinase 9 in the Medical Dictionary? cyclin-dependent kinase 9 explanation ... redirected from cyclin-dependent kinase 9). Also found in: Wikipedia. CDK9. A gene on chromosome 9q34.1 that encodes a cyclin- ... cyclin-dependent kinase inhibitor p57. *Cyclin-dependent kinase inhibitor proteins. *Cyclin-dependent kinase inhibitor proteins ...
Cyclin-dependent kinases 7 and 9 specifically regulate neutrophil transcription and their inhibition drives apoptosis to...
Delayed apoptosis, which is responsible for their extended longevity, is critically dependent o … ... Here, we elucidate the mechanism by which the cyclin-dependent kinase (CDK) inhibitor drugs such as R-roscovitine and DRB (5,6- ... Cyclin-dependent kinases 7 and 9 specifically regulate neutrophil transcription and their inhibition drives apoptosis to ... Delayed apoptosis, which is responsible for their extended longevity, is critically dependent on a balance of intracellular ...
AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor...
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 ...
AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor...
1). AZD5438 potently inhibited the kinase activity of cyclin E-cdk2, cyclin A-cdk2, cyclin B1-cdk1, p25-cdk5, cyclin D3-cdk6, ... including cyclin D-dependent kinases (41), extracellular signal-regulated kinase 1/2 (42), and transglutaminase 2 kinase (43). ... pyridine inhibitor of cyclin-dependent kinases 1 and 2, induces E2F-1-dependent apoptosis enhanced by depletion of cyclin- ... Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists. Proc Natl Acad Sci U S A 1999;96:4325- ...
A Novel pyrazolo[1,5-a]pyrimidine Is a Potent Inhibitor of Cyclin-Dependent Protein Kinases 1, 2, and 9, Which Demonstrates...
Cyclin-dependent protein kinases (CDKs) are central to the appropriate regulation of cell proliferation, apoptosis, and gene ... Cyclin-dependent protein kinases (CDKs) are central to the appropriate regulation of cell proliferation, apoptosis, and gene ... A Novel pyrazolo[1,5-a]pyrimidine Is a Potent Inhibitor of Cyclin-Dependent Protein Kinases 1, 2, and 9, Which Demonstrates ... down-regulation of cyclins A, E, and D1, and cell cycle block in the S and G₂/M phases. Consistent with these findings, 4k ...
Perspective of Cyclin-dependent kinase 9 (CDK9) as a Drug Target | Bentham Science
... cyclin-dependent kinases (CDKs), anticancer activity, chromosome condensation. Abstract:Deregulation of cyclin-dependent ... Keywords: Cancer, inflammation, kinase, P-TEFb, inhibitor, therapeutics, angiogenesis, cyclin-dependent kinases (CDKs), ... Perspective of Cyclin-dependent kinase 9 (CDK9) as a Drug Target. Author(s): Vladimir Krystof, Laboratory of Growth Regulators ... Deregulation of cyclin-dependent kinases (CDKs) has been associated with many cancer types and has evoked an interest in ...
RePub, Erasmus University Repository:
Differential proteomics based on 18O labeling to determine the cyclin dependent kinase...
18O labeling, cyclin dependent kinase 9, differential proteomics, interactome, nanoflow LC-MS/MS, protein-protein interactions, ... Differential proteomics based on 18O labeling to determine the cyclin dependent kinase 9 interactome. Publication. Publication ... Differential proteomics based on 18O labeling to determine the cyclin dependent kinase 9 interactome. Journal of Proteome ... differentiate between bona fide interaction partners of the low-level expressing cell cycle regulator cyclin-dependent kinase 9 ...
Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase...
Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit... ... 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 Direct. ... 92 Pages Report] Check for Discount on Cyclin Dependent Kinase 9 (Tat Associated ...
Role of cyclin-dependent Kinase 9 in the zebrafish embryonic heart
Potent anti-leukemic activity of a specific cyclin-dependent kinase 9 inhibitor in mouse models of chronic lymphocytic leukemia...
Potent anti-leukemic activity of a specific cyclin-dependent kinase 9 inhibitor in mouse models of chronic lymphocytic leukemia ... CDK6-Cyclin D3, CDK7-Cyclin H-MAT1), ProQinase (CDK2-Cyclin A) and Invitrogen (CDK9-Cyclin T1). Broad selectivity kinase in ... Up-regulation of CDK9 kinase activity and Mcl-1 stability contributes to the acquired resistance to cyclin-dependent kinase ... BCL-2, B-cell lymphoma/leukemia 2; BTK, Brutons tyrosine kinase; CDK9, cyclin-dependent kinase 9; CLL, chronic lymphocytic ...
Cyclin-Dependent Kinase 9 | REACH
CDC2-CDC28 Kinases [D08.811.913.696.620.682.700.646.500.500]. *Cyclin-Dependent Kinase 9 [D08.811.913.696.620.682.700.646. ... Proline-Directed Protein Kinases [D08.811.913.696.620.682.700.646]. *Cyclin-Dependent Kinases [D08.811.913.696.620.682.700.646. ... "Cyclin-Dependent Kinase 9" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ... This graph shows the total number of publications written about "Cyclin-Dependent Kinase 9" by people in this website by year, ...
Cyclin-Dependent Kinase 9 | ISHAR Online
Here, we elucidate the mechanism by which the cyclin-dependent kinase (CDK) inhibitor drugs such as R-roscovitine and DRB (5,6- ... Cyclin-dependent kinases 7 and 9 specifically regulate neutrophil transcription and their inhibition drives apoptosis to ... HIV-1 transcription is activated by HIV-1 Tat protein, which recruits cyclin-dependent kinase 9 (CDK9)/cyclin T1 and other host ... Delayed apoptosis, which is responsible for their extended longevity, is critically dependent on a balance of intracellular ...
Cyclin dependent kinase 9 (CDK9) - Molecular Target Profile - BioCentury - BCIQ
Comprehensive view of all products targeting Cyclin dependent kinase 9 (CDK9). Includes lead product status, indications and ... cyclin dependent kinase 9 (CDK9), that may broaden the scope of CDK9 inhibitors to include... ... 21:20 , Nov 9, 2018 , BC Innovations , Distillery Therapeutics Cancer INDICATION: Colorectal cancer; cancer In vitro , cell ... Cyclacel reports Phase I data for CDK2/9 inhibitor in solid tumors Cyclacel Pharmaceuticals Inc. (NASDAQ:CYCC) reported data ...
Cyclin Dependent Kinase 7 - Pipeline Review, H2 2017
Cyclin Dependent Kinase 7 (39 kDa Protein Kinase or CDK Activating Kinase 1 or Cell Division Protein Kinase 7 or TFIIH Basal ... Cyclin Dependent Kinase 7 (39 kDa Protein Kinase or CDK Activating Kinase 1 or Cell Division Protein Kinase 7 or TFIIH Basal ... Cyclin Dependent Kinase 7 (39 kDa Protein Kinase or CDK Activating Kinase 1 or Cell Division Protein Kinase 7 or TFIIH Basal ... Cyclin Dependent Kinase 7 (39 kDa Protein Kinase or CDK Activating Kinase 1 or Cell Division Protein Kinase 7 or TFIIH Basal ...
TP-1287, AN ORAL PRODRUG OF THE CYCLIN-DEPENDENT KINASE-9 INHIBITOR.... EHA Learning Center. Whatcott C. Jun 9 2016; 132440
Alvocidib is a potent inhibitor of cyclin-dependent kinase-9 (CDK9) and induces apoptosis in cancer cells by reducing the ... TP-1287, AN ORAL PRODRUG OF THE CYCLIN-DEPENDENT KINASE-9 INHIBITOR ALVOCIDIB ... dependent on MCL-1. Patients with AML that have a high dependence on MCL-1 are considered more likely to benefit from the ...
The Cyclin-Dependent Kinase Inhibitor Flavopiridol Potentiates Doxorubicin Efficacy in Advanced Sarcomas: Preclinical...
Cyclin-dependent kinases (CDK) are serine/threonine kinases that are activated upon association with cyclin proteins to form ... Fluorescent cyclin-dependent kinase inhibitors block the proliferation of human breast cancer cells. Bioorg Med Chem 2011;19: ... Flavopiridol, a novel cyclin-dependent kinase inhibitor, in clinical development. Ann Pharmacother 2002;36:905-11. ... Purpose: Dysregulated cyclin-dependent kinases are important to the growth of some sarcomas. Flavopiridol is a pan-CDK ...
RCSB PDB
for 4BCF
CYCLIN-DEPENDENT KINASE 9 A 331 Homo sapiens EC#: 2.7.11.22 IUBMB 2.7.11.23 IUBMB Fragment: RESIDUES 2-330 Mutation: G97A Gene ... CYCLIN-T1 B 260 Homo sapiens Fragment: RESIDUES 2-259 Mutation: Q77R, E96G, F241L Gene Name(s): CCNT1 Gene View ... Structure of CDK9 in complex with cyclin T and a 2-amino-4-heteroaryl- pyrimidine inhibitor. *DOI: 10.2210/pdb4bcf/pdb ...
Cyclin-dependent kinases 7 and 9 specifically regulate neutrophil transcription and their inhibition drives apoptosis to...
Here, we elucidate the mechanism by which the cyclin-dependent kinase (CDK) inhibitor drugs such as R-roscovitine and DRB (5,6- ... Cyclin-dependent kinases 7 and 9 specifically regulate neutrophil transcription and their inhibition drives apoptosis to ... "Cyclin-dependent kinases 7 and 9 specifically regulate neutrophil transcription and their inhibition drives apoptosis to ... Cyclin-dependent kinases 7 and 9 specifically regulate neutrophil transcription and their inhibition drives apoptosis to ...
Cyclin-dependent kinase-9 is a therapeutic target in MYC-expressing diffuse large B-cell lymphoma<...
Cyclin-dependent kinase-9 is a therapeutic target in MYC-expressing diffuse large B-cell lymphoma. / Hashiguchi, Taylor; Bruss ... Cyclin-dependent kinase-9 is a therapeutic target in MYC-expressing diffuse large B-cell lymphoma. Molecular cancer ... title = "Cyclin-dependent kinase-9 is a therapeutic target in MYC-expressing diffuse large B-cell lymphoma", ... T1 - Cyclin-dependent kinase-9 is a therapeutic target in MYC-expressing diffuse large B-cell lymphoma ...
Systematic determination of human cyclin dependent kinase (CDK)-9 interactome identifies novel functions in RNA splicing...
Fingerprint Dive into the research topics of Systematic determination of human cyclin dependent kinase (CDK)-9 interactome ... Here, the recruitment of a multifunctional complex containing the cyclin dependent kinase 9 (CDK9) triggers the process of ... Here, the recruitment of a multifunctional complex containing the cyclin dependent kinase 9 (CDK9) triggers the process of ... Here, the recruitment of a multifunctional complex containing the cyclin dependent kinase 9 (CDK9) triggers the process of ...
anti-CDK9 antibody (Cyclin-Dependent Kinase 9) (N-Term)</span...
C-2K and Cell division cycle 2-like protein kinase 4) is a member of the cyclin-dependent protein kinase (CDK) family. CDK ... anti-CDK9 antibody (Cyclin-Dependent Kinase 9) (N-Term) CDK9 antibody (Cyclin-Dependent Kinase 9) (N-Term). Details for Product ... Cyclin-Dependent Kinase 9 Epitope N-Term, C-Term Alternatives 33 pThr186. ... Images for product: anti-Cyclin-Dependent Kinase 9 (CDK9) (C-Term), (N-Term) antibody ...
CDK9InhibitorsCDKsProteinsSerineSubunitElongationInhibitionComplexesCdk7Inhibitor of cyclin-dependeTyrosineExpression of cyclin-depend2018PhosphorylateCDK2RegulationInhibitTumorSubunitsChromosomeProgressionRegulatePotent inhibitorApoptosisSmall moleculePathwaysRegulatorRegulatorsMitogen-activaMolecularTumors1997Cdk1EnzymePromoterComplexActivity2021Cdc2Roscovitine2001Polymerase IICDK5
CDK942
- Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb. (wikipedia.org)
- Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase 4 or Cell Division Protein Kinase 9 or Serine/Threonine Protein Kinase PITALR or CDK9 or EC 2.7.11.22 or EC 2.7.11.23) - Cyclin-dependent kinase 9 (CDK9) is a cyclin-dependent kinase associated with P-TEFb. (medindia.net)
- Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase 4 or Cell Division Protein Kinase 9 or Serine/Threonine Protein Kinase PITALR or CDK9 or EC 2.7.11.22 or EC 2.7.11.23) pipeline Target constitutes close to 26 molecules. (medindia.net)
- It also reviews key players involved in Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase 4 or Cell Division Protein Kinase 9 or Serine/Threonine Protein Kinase PITALR or CDK9 or EC 2.7.11.22 or EC 2.7.11.23) targeted therapeutics development with respective active and dormant or discontinued projects. (medindia.net)
- Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. (uniprot.org)
- The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. (uniprot.org)
- the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage. (uniprot.org)
- Strikingly, RNA polymerase II (RNAPII) is itself a substrate for two protein kinases-the cyclin-dependent kinases Cdk7 and Cdk9-that are activated by hypertrophic cues. (ahajournals.org)
- Cdk9 interacts adversely with Gq-dependent pathways for hypertrophy, impairing the expression of numerous genes for mitochondrial proteins, and, in particular, suppressing master regulators of mitochondrial biogenesis and function, perioxisome proliferator-activated receptor-γ coactivator-1 (PGC-1), and nuclear respiratory factor-1 (NRF-1). (ahajournals.org)
- In this study, we show that, after UV irradiation, the cyclin-dependent kinase 9 (CDK9)/cyclin T1 kinase unit is specifically released from the HEXIM1 complex and that this released fraction is degraded in the absence of the Cockayne syndrome group B protein (CSB). (nih.gov)
- CDK9 is present in two isoforms termed CDK9-42 and CDK9-55 that bind noncovalently type T cyclins and cyclin K. This association forms a heterodimer, where CDK9 carries the enzymatic site and the cyclin partner functions as a regulatory subunit. (hindawi.com)
- This review describes the CDK9-related pathway deregulations in malignancies and the development of kinase inhibitors in cancer therapy, which can be classified into three categories: antagonists that block the ATP binding site of the catalytic domain, allosteric inhibitors, and small molecules that disrupt protein-protein interactions. (hindawi.com)
- HIV-1 Tat protein interacts with CDK9 and cyclin T, suggesting CDK9 may have a role in AIDS. (thefreedictionary.com)
- Study TPI-ALV-201 is examining the efficiency of alvocidib, an investigational inhibitor of cyclin-dependent kinase 9 (CDK9), in combination with the authorized agents cytarabine and mitoxantrone in relapsed/refractory AML patients whose leukemia depends on MCL-1. (thefreedictionary.com)
- Biopharmaceutical company Probiodrug AG revealed on Friday the transfer of its experimental cyclin-dependent kinase 9 (CDK9) inhibitor programme to AstraZeneca (LSE:AZN)(NYSE:AZN) for an undisclosed amount. (thefreedictionary.com)
- Vladimir Krystof, Sonja Baumli and Robert Furst, "Perspective of Cyclin-dependent kinase 9 (CDK9) as a Drug Target", Current Pharmaceutical Design (2012) 18: 2883. (eurekaselect.com)
- We have implemented this approach into a protein-protein interaction analysis pipeline to differentiate between bona fide interaction partners of the low-level expressing cell cycle regulator cyclin-dependent kinase 9 (Cdk9) and nonspecifically binding or background proteins. (eur.nl)
- Cyclin-dependent Kinase 9 (CDK9), part of a family of proteins controlling cell cycle and growth, has emerged as one such potential candidate over the last 5 years. (ed.ac.uk)
- 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)
- A team led by Temple University scientists has shed light on a new epigenetic mechanism behind a known cancer target, cyclin dependent kinase 9 (CDK9), that may broaden the scope of CDK9 inhibitors to include. (biocentury.com)
- Alvocidib is a potent inhibitor of cyclin-dependent kinase-9 (CDK9) and induces apoptosis in cancer cells by reducing the expression of short-lived, anti-apoptotic protein such as MCL-1. (ehaweb.org)
- A key feature in its ability to stimulate RNA Pol II activity is recruitment of pTEFb, an elongation factor whose catalytic core comprises CDK9/cyclin T complexes. (elsevier.com)
- CDK9 inhibition downregulated Mcl-1 and MYC mRNA transcript and protein in a dose-dependent manner. (elsevier.com)
- 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. (utmb.edu)
- These data identified that CDK9 interacts with DDX 5/17, a family of ATP-dependent RNA helicases, important in alternative RNA splicing of NFAT5, and mH2A1 mRNA two proteins controlling redox signaling. (utmb.edu)
- Recruited into the CDK9 interactome in response to poly(I:C) stimulation are HSPB1, DNA dependent kinases, and cytoskeletal myosin proteins that exchange with 60S ribosomal structural proteins. (utmb.edu)
- These data were used to develop a probabilistic global map of CDK9-dependent target genes that predicted two functional states controlling distinct cellular functions, one important in immune and stress responses. (utmb.edu)
- CCNK and its kinase partner CDK9 are subunits of the transcription elongation factor pTEFB. (abcam.com)
- Kinase Assay demonstrating CDK9/CyclinK specific activity. (abcam.com)
- The CDK9/cyclin-K complex has also a kinase activity toward CTD of RNAP II and can substitute for P-TEFb in vitro. (abcam.com)
- It is now becoming clear, however, that the regulation of transcription elongation in addition to initiation by EBNA 2, at least in part through CDK9 (cyclin-dependent kinase 9)-dependent phosphorylation of the RNA polymerase C-terminal domain, is likely to play a crucial role in the mechanism of action of this key viral protein. (biochemsoctrans.org)
- This cyclin tightly associates with CDK9 kinase, and was found to be a major subunit of the transcription elongation factor p-TEFb. (abnova.com)
- Our current work is focused on a network involving at least three distinct small non-coding (snc) RNAs, which work synergistically to adjust the levels of synthesis and activity of a pleiotropic protein, the cyclin-dependent kinase 9 (Cdk9), part of the heterodimeric complex designated P-TEFb. (frontiersin.org)
- The Cdk9 protein is associated with a cyclin from either the T or the K families in the heterodimer P-TEFb, which plays a key role in the Polymerase II transcription machinery ( Kohoutek, 2009 ). (frontiersin.org)
- The Cdk9 component functions as the catalytic domain, while the cyclin constitutes the regulatory subunit ( Malumbres and Barbacid, 2005 ). (frontiersin.org)
- In many human cell types, the predominant form of P-TEFb consists of cyclin-dependent kinase 9 (CDK9) and its regulatory partner, cyclin T1 ( 11 ). (aacrjournals.org)
- We recently found that the viral RNA transcription of DNA viruses requires cyclin dependent kinase 9 (CDK9) in the host cells, and that FIT039, a specific inhibitor of CDK9, suppressed the proliferation of DNA viruses such as herpes simplex virus 1 (HSV-1), HSV-2, human adenovirus, human cytomegalovirus, hepatitis virus B, and HPVs. (nii.ac.jp)
- The company is also developing KB-0742, an oral inhibitor of cyclin dependent kinase 9 (CDK9), for the treatment of MYC-dependent solid tumors. (biospace.com)
- Cyclin K interacts with CDK12 and CDK13 but not CDK9 in cells, and is required to maintain self-renewal in ES cells. (antibodies-online.com)
- Cyclin K inhibits HIV-1 gene expression and replication by interfering with cyclin-dependent kinase 9 (CDK9)-cyclin T1 interaction in Nef-dependent manner. (antibodies-online.com)
- These results reveal an unexpectedly direct role for CDK9-cyclin K in checkpoint pathways that maintain genome integrity in response to replication stress. (antibodies-online.com)
- P-TEFb containing cyclin K and Cdk9 can activate transcription via RNA. (antibodies-online.com)
Inhibitors18
- These studies may lead to the improvement of kinase inhibitors for the treatment of the previously mentioned pathological conditions. (hindawi.com)
- Despite the lack of selective cdk1 inhibitors being described, dual cdk1-cdk2 inhibitors have been reported ( 12 - 14 ) and combined depletion of cdk1 and cdk2 is more proapoptotic than depletion of either cdk alone ( 9 ). (aacrjournals.org)
- Deregulation of cyclin-dependent kinases (CDKs) has been associated with many cancer types and has evoked an interest in chemical inhibitors with possible therapeutic benefit. (eurekaselect.com)
- Here, we show that the block to IE gene expression during S and G2 phase can be overcome by both genotoxic stress and chemical inhibitors of cellular DNA replication, pointing to the involvement of checkpoint-dependent signaling pathways in controlling IE gene repression. (prolekare.cz)
- The Kinase Enzyme Systems allow you to easily screen and profile kinase inhibitors. (promega.com)
- CDK4, for instance, is positively regulated by cyclin D and can be inhibited by binding to members of the inhibitors of CDK4 (INK4) family, which act by preventing association of the CDK4 catalytic subunit to the positive regulator cyclin D1. (jneurosci.org)
- Inhibitors of the kinase inhibitory protein (Kip) family can also bind CDK4/cyclin D complexes, although with lower affinity than the INKs, but this event does not result in efficient functional inhibition of enzymatic activity ( Sherr and Roberts, 1995 ). (jneurosci.org)
- Calcitriol induces a significant G 0 /G 1 arrest and modulates p21 Waf1/Cip1 and p27 Kip1 , the cyclin dependent kinase inhibitors. (springer.com)
- The novel class of agents called inhibitors of cyclin-dependent kinases (or "CDK inhibitors") has shown promise in therapy of cancer. (lls.org)
- Eukaryotic cell cycle progression is regulated by cyclin-dependent kinases (CDKs), which phosphorylate and dephosphorylate binding proteins such as cyclins and CDK inhibitors (CKIs) ( Morgan, 1995 ). (aspetjournals.org)
- Here, we show that menin directly regulates expression of the cyclin-dependent kinase inhibitors p27 Kip1 and p18 Ink4c . (pnas.org)
- Pituitary cyclin E/E2F1 signaling is a previously unappreciated molecular mechanism underlying neuroendocrine regulation of the hypothalamic-pituitary-adrenal axis, providing a subcellular therapeutic target for small molecule cyclin-dependent kinase 2 inhibitors of pituitary ACTH-dependent hypercortisolism, ie, Cushing disease. (sigmaaldrich.com)
- 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)
- Flavopiridol and roscovitine, newly identified inhibitors of cyclin-dependent kinase-9, markedly decrease HIV-1 promoter activity in cell lines of various lineages. (asnjournals.org)
- Thus, suppression of HIV-1 transcription by selective cyclin-dependent kinase-9 inhibitors may be a useful therapeutic strategy for the treatment of HIVAN. (asnjournals.org)
- Kronos Bio is developing a portfolio of spleen tyrosine kinase (SYK) inhibitors, entospletinib (ENTO) and lanraplenib (LANRA), for the treatment of NPM1-mutated and FLT3-mutated acute myeloid leukemia (AML). (biospace.com)
- Next-generation cyclin dependent kinase 2/9 (CDK2/9) inhibitors offer a new way to kill lung cancer while doing minimal harm to normal cells. (mdanderson.org)
- Our results further showed that JAK3 inhibitor VI function was independent of JAK kinases but involved downregulation of cathepsin L. We postulate that the screening method and the verification experiments that are based on oncogene‐induced changes in lysosomal hydrolase activity and lysosomal distribution could be used for identification of novel inhibitors of ErbB2‐induced invasiveness. (pubmedcentralcanada.ca)
CDKs14
- We demonstrate (by a combination of microarray, confocal microscopy, apoptosis assays and western blotting) that the phosphorylation of RNA polymerase II by CDKs 7 and 9 is inhibited by R-roscovitine and that specific effects on neutrophil transcriptional capacity are responsible for neutrophil apoptosis. (nih.gov)
- 5 , 6 ) has evolved to incorporate novel activities of cyclin-cdk complexes that have been observed in response to certain conditions, particularly when specific cdks are depleted (reviewed in ref. 7 ). (aacrjournals.org)
- It seems that functional redundancy among cdks and cyclin binding partners is a frequent event bringing clear implications for the clinical utility of selective cdk inhibition. (aacrjournals.org)
- Cyclin-dependent protein kinases (CDKs) are central to the appropriate regulation of cell proliferation, apoptosis, and gene expression. (nih.gov)
- CDKs are attractive targets for drug development, given that certain malignancies are dependent on dysregulated cyclin activity ( 1 ) and CDK inhibition has been observed as a potent vehicle to overcome resistance to standard chemotherapy ( 2-4 ). (aacrjournals.org)
- Requirement for the cyclin dependent kinase (CDK) inhibitor p21 downstream of p53 suggests a pivotal role for CDKs in controlling IE gene repression in S/G2 and treatment of S/G2 cells with the CDK inhibitor roscovitine alleviates IE repression independently of p53. (prolekare.cz)
- and is modulated by the enzymatic activity of cyclin-dependent kinases (CDKs). (jneurosci.org)
- Cdks (cyclin-dependent kinases) are heteromeric serine/threonine kinases that control progression through the cell cycle in concert with their regulatory subunits, the cyclins. (genecards.org)
- Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. (wikipedia.org)
- CDKs are relatively small proteins, with molecular weights ranging from 34 to 40 kDa, and contain little more than the kinase domain. (wikipedia.org)
- CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases. (wikipedia.org)
- The structure of human Cdk2 revealed that CDKs have a modified ATP-binding site that can be regulated by cyclin binding. (wikipedia.org)
- Cell cycle progression may be also regulated, independently of cyclins and CDKs, thanks to the strong affinity binding to proliferating cell nuclear antigen (PCNA) [ 14 - 17 ], a protein playing a central role in DNA replication and repair, as well as in other processes of DNA metabolism [ 18 , 19 ]. (intechopen.com)
- Dowejko, Bauer, Bauer, Müller-Richter, Reichert: The human HECA interacts with cyclins and CDKs to antagonize Wnt-mediated proliferation and chemoresistance of head and neck cancer cells. (antibodies-online.com)
Proteins10
- Delayed apoptosis, which is responsible for their extended longevity, is critically dependent on a balance of intracellular survival versus pro-apoptotic proteins. (nih.gov)
- Cyclin-dependent kinases (CDK) are serine/threonine kinases that are activated upon association with cyclin proteins to form CDK complexes. (aacrjournals.org)
- Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. (wikipedia.org)
- only the cyclin-CDK complex is an active kinase but its activity can be typically further modulated by phosphorylation and other binding proteins, like p27. (wikipedia.org)
- Substrate specificity of S cyclins is imparted by the hydrophobic batch (centered on the MRAIL sequence), which has affinity for substrate proteins that contain a hydrophobic RXL (or Cy) motif. (wikipedia.org)
- Cyclin-dependent kinases are proteins which exist in cells under normal conditions. (lls.org)
- Database mining confirmed ~2000 mitotic phosphotyrosine sites, and network analysis revealed a number of subnetworks that were enriched in tyrosine-phosphorylated proteins, including components of the kinetochore or spindle and SRC family kinases. (sciencemag.org)
- Due to the lack of a defined tertiary structure, p21 protein may adopt an extended conformation [ 9 ], which may explain its ability to interact with a number of proteins involved in several important biological processes [ 3 - 6 ] ( Figure 1) . (intechopen.com)
- Additionally we are shipping Cyclin K Kits (12) and Cyclin K Proteins (7) and many more products for this protein. (antibodies-online.com)
- We present a list of cellular host kinases and other proteins that interact with these kinases. (scirp.org)
Serine9
- Cyclin Dependent Kinase 7 (39 kDa Protein Kinase or CDK Activating Kinase 1 or Cell Division Protein Kinase 7 or TFIIH Basal Transcription Factor Complex Kinase Subunit or Serine/Threonine Protein Kinase 1 or CDK7 or EC 2.7.11.22 or EC 2.7.11.23) - Cell division protein kinase 7 is an enzyme that in humans is encoded by the CDK7 gene. (researchandmarkets.com)
- Cyclin Dependent Kinase 7 (39 kDa Protein Kinase or CDK Activating Kinase 1 or Cell Division Protein Kinase 7 or TFIIH Basal Transcription Factor Complex Kinase Subunit or Serine/Threonine Protein Kinase 1 or CDK7 or EC 2.7.11.22 or EC 2.7.11.23) pipeline Target constitutes close to 11 molecules. (researchandmarkets.com)
- This gene product is a member of a large family of CDC2-related serine/threonine protein kinases that accumulates primarily in the nucleus. (nih.gov)
- Its serine-threonine kinase activity plays an essential role in RNA polymerase II transcription and is currently recognized as a critical actor in a number of physiological and pathological processes. (frontiersin.org)
- Increased HEXIM1 expression in the mammary gland decreased estrogen-driven ductal morphogenesis and inhibited the expression of cyclin D1 and serine 2 phosphorylated RNA polymerase II (S2P RNAP II). (aacrjournals.org)
- The RNAP II CTD consists of multiple repeats of the heptapeptide sequence, YSPTSPS, phosphorylated at serine 5 by general transcription factor TFIIH during initiation and at serine 2 by P-TEFb during elongation ( 9 , 10 ). (aacrjournals.org)
- The cell cycle is a carefully controlled process in which serine/threonine kinases play a large role. (sciencemag.org)
- For example, in their network generated from data mining and in cultured cells, tyrosine phosphorylation decreased activation of Polo-like kinase 1 (PLK1), a serine/threonine kinase that promotes chromosome separation during anaphase and is often excessively abundant in cancers. (sciencemag.org)
- Additionally IPA analysis indicated that these modified host cellular kinases are known to have interactions with each other especially AKT1, a serine/threonine kinase involved in multiple pathways. (scirp.org)
Subunit8
- 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. (wikipedia.org)
- This protein forms a complex with and is regulated by its regulatory subunit cyclin T or cyclin K. HIV-1 Tat protein was found to interact with this protein and cyclin T, which suggested a possible involvement of this protein in AIDS. (wikipedia.org)
- CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. (researchandmarkets.com)
- It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (wikipedia.org)
- Cell division protein kinase 7 (EC 2.7.11.22) (EC 2.7.11.23) (CDK- activating kinase) (CAK) (TFIIH basal transcription factor complex kinase subunit) (39 kDa protein kinase) (P39 Mo15) (STK1) (CAK1). (ebi.ac.uk)
- This cyclin and its kinase partner were also found to be involved in the phosphorylation and regulation of the carboxy-terminal domain (CTD) of the largest RNA polymerase II subunit. (abnova.com)
- 1988 ) Activation of cdc2 protein kinase during mitosis in human cells: cell cycle-dependent phosphorylation and subunit rearrangement. (biologists.org)
- It also phosphorylates the COOH-terminal repeat domain (CTD) of the largest subunit of RNAP II ( 9 , 10 ). (aacrjournals.org)
Elongation4
- A multifunctional CDC2 kinase-related kinase that plays roles in transcriptional elongation, CELL DIFFERENTIATION, and APOPTOSIS. (sickkids.ca)
- The kinase complex containing this cyclin and the elongation factor can interact with, and act as a cofactor of human immunodeficiency virus type 1 (HIV-1) Tat protein, and was shown to be both necessary and sufficient for full activation of viral transcription. (abnova.com)
- In eukaryotic transcription, the elongation stage is highly regulated and important for the generation of full-length mRNA transcripts ( 9 - 11 ). (aacrjournals.org)
- One of the positive regulators, positive transcription elongation factor b (P-TEFb), has an essential role in RNA polymerase II (RNAP II) transcription elongation ( 9 , 10 ). (aacrjournals.org)
Inhibition8
- Finally, we show that specific CDK7 and 9 inhibition with DRB drives resolution of neutrophil-dominant inflammation. (nih.gov)
- Promiscuity among cdk-cyclin binding partners has been observed both in vivo and in vitro and could drive resistance in the clinic ( 8 , 9 ), with a growing number of studies indicating that highly selective cdk inhibition may not be therapeutically effective. (aacrjournals.org)
- Inhibition of cdk1 rapidly down-regulates survivin expression-inducing MYC-dependent apoptosis, leading to the suggestion that cdk1 inhibition might be a useful therapy for tumors that overexpress MYC, for example, in Burkitt's lymphoma ( 16 ). (aacrjournals.org)
- Cell-based studies showed inhibition of the phosphorylation of CDK substrates, Rb and the RNA polymerase II C-terminal domain, down-regulation of cyclins A, E, and D1, and cell cycle block in the S and G₂/M phases. (nih.gov)
- Checkpoint-dependent rescue of IE expression strictly requires p53 and in the absence of checkpoint activation is mimicked by proteasomal inhibition in a p53 dependent manner. (prolekare.cz)
- In a corollary in vivo study, YC-1 induced dose-dependent inhibition of tumor growth in mice inoculated with HA22T cells. (aspetjournals.org)
- This study on adult T-cell leukemia/lymphoma, an aggressive malignancy of activated T-cells, brings convincing in vivo evidence that highly specific cyclin-dependent kinase 9 inhibition could be therapeutically effective. (bloodjournal.org)
- Data shows that these cancer cell lines were sensitive to CDK1/2/9 inhibition, however the most aggressive (SUM159 and MDA-MB-231) cells were less susceptible. (selleckchem.com)
Complexes11
- [5] Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. (wikipedia.org)
- Cyclin D-CDK4 complexes are major integrators of various mitogenic and antimitogenic signals. (wikipedia.org)
- Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. (genecards.org)
- Most of the known cyclin-CDK complexes regulate the progression through the cell cycle. (wikipedia.org)
- Cyclin-CDK complexes phosphorylate substrates appropriate for the particular cell cycle phase. (wikipedia.org)
- Cyclin-CDK complexes of earlier cell-cycle phase help activate cyclin-CDK complexes in later phase. (wikipedia.org)
- The INK4 family consists of p16 INK4a , p15 INK4b , p18 INK4c , and p19 INK4d , which narrow specifically to form stale complexes with CDK4/6 before binding with cyclin D ( Vidal and Koff, 2000 ). (aspetjournals.org)
- The main role of p21 is cell-cycle regulation, performed by inhibiting the activity of cyclin-CDK complexes thanks to direct interaction through specific sequences (termed CDK and Cy motifs) in the N-terminal domain of the protein [ 10 - 13 ]. (intechopen.com)
- In contrast with the negative cell-cycle regulation, p21 may also serve as an assembly factor for cyclin D-CDK4/6 complexes, thus promoting cyclin D-dependent events, and downstream activation of cyclin E-CDK2 [ 7 , 8 ]. (intechopen.com)
- SETD1A and cyclin K complexes may represent a therapeutic opportunity for acute myeloid leukemia and, potentially, for other cancers. (antibodies-online.com)
- Cyclin K-containing kinase complexes maintain self-renewal in murine embryonic stem cells. (antibodies-online.com)
Cdk72
- Another one, CDK7, is involved indirectly as the CDK-activating kinase. (wikipedia.org)
- Cell division protein kinase 7 is an enzyme that in humans is encoded by the CDK7 gene . (wikidoc.org)
Inhibitor of cyclin-depende2
- A transcriptional regulation program is evaluating lead asset CYC065, a dual inhibitor of cyclin dependent kinases (CDK) 2 and 9, in patients with advanced cancers. (cyclacel.com)
- A highly-selective, orally-available, 2nd generation inhibitor of cyclin dependent kinases (CDK) 2 and 9. (cyclacel.com)
Tyrosine5
- This will likely also hold true in the current era of novel anti-CLL drug approvals targeting Bruton's tyrosine kinase (BTK), phosphatidylinositol-3-kinase delta (PI3Kδ) and B-cell lymphoma/leukemia 2 (BCL-2) [ 8 ]. (oncotarget.com)
- Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity . (genecards.org)
- One of the kinases that place the tyrosine phosphate is Wee1, a kinase conserved in all eukaryotes. (wikipedia.org)
- cytoplasmic tyrosine kinase Dscr28C rel. (wikipathways.org)
- The activation of cyclin-CDK complex can be inhibited by phosphorylation of a conserved threonine-tyrosine pair in CDK or by association with CKIs ( Elledge, 1996 ). (aspetjournals.org)
Expression of cyclin-depend1
- Of note, YC-1 induced a dramatic increase in the expression of cyclin-dependent kinase (CDK)-inhibitory protein, p21 CIP1/WAP1 , and a modest increase in p27 KIP1 . (aspetjournals.org)
20181
- 2018 , 9 , Article number: 3805. (imperial.ac.uk)
Phosphorylate1
- Cyclin K1 is the primary cyclin partner for CDK12/CrkRS and it is required for activation of CDK12/CrkRS to phosphorylate the C-terminal domain of RNA Pol II. (antibodies-online.com)
CDK25
- CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. (researchandmarkets.com)
- Last fall we initiated a first-in-human, Phase 1 study of CYC065, our second-generation CDK2/9 inhibitor, in patients with solid tumors and lymphomas following extensive preclinical data in the literature suggesting broad activity of CYC065 in both liquid and solid tumor models. (cnbc.com)
- Continued patient recruitment in the first-in-human trial of CYC065, a second-generation CDK2/9 inhibitor, to evaluate the safety, tolerability and pharmacokinetic profile of CYC065 in patients with solid tumors and lymphomas. (cnbc.com)
- CDK2, in contrast, is positively regulated by cyclin E and negatively regulated by the Kips. (jneurosci.org)
- YC-1 did not modify the expression of cyclin D1, cyclin E, CDK2, or CDK4. (aspetjournals.org)
Regulation14
- Protein kinase involved in the regulation of transcription. (uniprot.org)
- Alvocidib is an investigational small molecule inhibitor of cyclin-dependent kinase 9 , a protein important to the regulation of Myc. (thefreedictionary.com)
- Cyclin K (CCNK) belongs to the highly conserved cyclin family and is thought to play a role in transcriptional regulation. (abcam.com)
- cyclin L CDK levels remain relatively constant throughout the cell cycle and most regulation is post-translational. (wikipedia.org)
- The four major mechanisms of CDK regulation are cyclin binding, CAK phosphorylation, regulatory inhibitory phosphorylation, and binding of CDK inhibitory subunits (CKIs). (wikipedia.org)
- Calcitriol induces PARP cleavage, increases the bax/bcl-2 ratio, reduces levels of phosphorylated mitogen-activated protein kinases (P-MAPKs, P-Erk-1/2) and phosphorylated Akt (P-Akt), induces caspase-dependent MEK cleavage and up-regulation of MEKK-1, all potential markers of the apoptotic pathway. (springer.com)
- Evaluation of cyclin-dependent kinase-like 1 expression in breast cancer tissues and its regulation in cancer cell growth. (nih.gov)
- These findings suggest that regulation of cyclin-dependent kinase inhibitor transcription by cooperative interaction between menin and MLL plays a central role in menin's activity as a tumor suppressor. (pnas.org)
- In addition, increased HEXIM1 expression in MCF-7 cells led to a decrease in estrogen-induced cyclin D1 expression, whereas down-regulation of HEXIM1 expression led to an enhancement of estrogen-induced cyclin D1 expression. (aacrjournals.org)
- In contrast to the PI 3-kinase-mediated pathway, little is known on the specific effects of exendin-4 on cell cycle regulation in β-cells via the cAMP-CREB-signaling pathway ( 9 ). (diabetesjournals.org)
- In addition, we have used a mouse model with specific nuclear upregulation of cAMP-CREB-CREB binding protein (CBP) action and enhanced in vivo and in vitro β-cell proliferation ( 9 ) to specifically assess the role of cAMP-CREB-regulated transcription on cell cycle regulation. (diabetesjournals.org)
- Cyclin E-Mediated Human Proopiomelanocortin Regulation as a Therapeutic Target for Cushing Disease. (sigmaaldrich.com)
- Cyclin E and E2F1 exhibit reciprocal positive regulation in corticotroph tumors. (sigmaaldrich.com)
- A mitosis regulation program is investigating CYC140, a polo-like kinase 1 inhibitor, in cancer patients. (cyclacel.com)
Inhibit3
- 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)
- Recently, flavopiridol and roscovitine, small molecules that inactivate specific cell-cycle cyclin-dependent kinases (CDK), were found to inhibit CDK-9, markedly decreasing HIV-1 promoter activity in cell lines of various lineages ( 8 , 9 ). (asnjournals.org)
Tumor8
- Flavopiridol has been tested at various dosing levels and schedules in both hematologic ( 7, 8 ) and solid tumor malignancies ( 3 , 9 , 10 ). (aacrjournals.org)
- We hypothesized that intrapituitary cyclin E signaling regulates corticotroph tumor POMC transcription independently of cell cycle progression. (sigmaaldrich.com)
- Cyclin E and E2F transcription factor 1 (E2F1) small interfering RNA (siRNA) transfection was performed in murine corticotroph tumor AtT20 cells to elucidate mechanisms for drug action. (sigmaaldrich.com)
- R-roscovitine inhibits human pituitary corticotroph tumor ACTH by targeting the cyclin E/E2F1 pathway. (sigmaaldrich.com)
- A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. (harvard.edu)
- Extracellular-Regulated Protein Kinase 5-Mediated Control of p21 Expression Promotes Macrophage Proliferation Associated with Tumor Growth and Metastasis. (harvard.edu)
- The crucial role of DNA-dependent protein kinase and myelin transcription factor 1-like protein in the miR-141 tumor suppressor network. (harvard.edu)
- Here, we observed antitumor activity following combinatorial therapy with anti-PD1 Ab and the cyclin-dependent kinase inhibitor dinaciclib in immunocompetent mouse tumor models. (jci.org)
Subunits1
- The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16 INK4a . (wikipedia.org)
Chromosome3
- A gene on chromosome 9q34.1 that encodes a cyclin-dependent kinase, which regulates cell cycle progression. (thefreedictionary.com)
- 1996 ) Vanadate triggers the transition from chromosome condensation to decondensation in a mitotic mutant (tsTM13) inactivation of p34cdc2/H1 kinase and dephosphorylation of mitosis-specific histone H3. (biologists.org)
- CDKN2A , also known as cyclin-dependent kinase Inhibitor 2A, is a gene on chromosome 9. (snpedia.com)
Progression3
- Results from RNA interference experiments indicate that at least one of these kinases is required for cell-cycle progression during meiosis and mitosis. (biologists.org)
- Here we report that the correct timing of cell cycle withdrawal in the developing organ of Corti requires p27(Kip1), a cyclin-dependent kinase inhibitor that functions as an inhibitor of cell cycle progression. (biologists.org)
- Because cyclin A2 was stimulated by cAMP, we assessed the role of cylcin A2 in cell cycle progression in Min6 and isolated islet β-cells. (diabetesjournals.org)
Regulate3
- CDK8 and cyclin C associate with the mediator complex and regulate transcription by several mechanisms. (wikipedia.org)
- Various kinases and phosphatases regulate their phosphorylation state. (wikipedia.org)
- It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18. (curehunter.com)
Potent inhibitor2
- We have developed AZD5438, a 4-(1-isopropyl-2-methylimidazol-5-yl)-2-(4-methylsulphonylanilino) pyrimidine, as a potent inhibitor of cyclin-dependent kinase (cdk) 1, 2, and 9 (IC 50 , 16, 6, and 20 nmol/L, respectively). (aacrjournals.org)
- AZD5438 is a potent inhibitor of CDK1/2/9 with IC50 of 16 nM/6 nM/20 nM in cell-free assays. (selleckchem.com)
Apoptosis2
- Here, we elucidate the mechanism by which the cyclin-dependent kinase (CDK) inhibitor drugs such as R-roscovitine and DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) mediate neutrophil apoptosis. (nih.gov)
- It works by inhibiting cyclin-dependent kinases, arresting cell division and causing apoptosis in non-small lung cancer cells. (drugbank.ca)
Small molecule1
- Experiments using cells taken from transgenic mice lacking SIRT1 demonstrated that introducing human SIRT1 enzymes increased Tat's transcriptional effects in a dose-dependent manner, while treating cells with the small molecule HR73, a derivative of a molecule that inhibits the yeast version of the SIRT1 protein, caused a 5-fold reduction in HIV transcription. (bio-medicine.org)
Pathways4
- CAK activity is not regulated by known cell-cycle pathways and cyclin binding is the limiting step for CDK activation. (wikipedia.org)
- It was further shown that cGMP, p42/p44 mitogen-activated protein kinase, or AKT kinase-mediated signaling pathways did not contribute to the YC-1-induced effect. (aspetjournals.org)
- R-roscovitine disrupts E2F1 binding to the POMC gene promoter and suppresses Tpit/Tbx19 and other lineage-specific POMC transcription cofactors via E2F1-dependent and -independent pathways. (sigmaaldrich.com)
- We used Qiagen Ingenuity Pathway Analysis (IPA) software to review the function of several cellular kinases and the resulting perturbed signaling pathways during HIV infection such as NF-κB signaling. (scirp.org)
Regulator1
- Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. (curehunter.com)
Regulators3
- In virtually all tumors, gene amplifications and/or deletions or functional alterations of key regulators contrive to deregulate the cyclin D1-cyclin-dependent kinase (cdk) 4/p16/pRb/E2F signaling axis ( 1 ) and, in the case of p27 and cyclin E, have prognostic value ( 2 , 3 ). (aacrjournals.org)
- Cyclins function as regulators of CDK kinases. (abnova.com)
- RESEARCH DESIGN AND METHODS- Changes in islet protein levels of cyclins and of two critical cell cycle regulators cyclin kinase inhibitor p27 and S-phase kinase-associated protein 2 (Skp2) were assessed in mice treated with exendin-4 and in a mouse model with specific upregulation of nuclear cAMP signaling exhibiting increased β-cell proliferation (CBP-S436A mouse). (diabetesjournals.org)
Mitogen-activa2
Molecular2
- Molecular cancer therapeutics , 18 (9), 1520-1532. (elsevier.com)
- Cyclin-dependent kinase 9 as a potential specific molecular target in NK cell leukemia/lymphoma. (amedeo.com)
Tumors2
- Targeting cyclin D1, a downstream effector of INI1/hSNF5, in rhabdoid tumors. (springer.com)
- The aim was to investigate whether R-roscovitine inhibits human ACTH in corticotroph tumors by targeting the cyclin-dependent kinase 2/cyclin E signaling pathway. (sigmaaldrich.com)
19971
- 1997 ) Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27Kip1. (biologists.org)
Cdk12
- In mammalian cells, CDK1, with its partners cyclin A2 and B1, alone can drive the cell cycle. (wikipedia.org)
- Cyclin B1 and B2 can localize Cdk1 to the nucleus and the Golgi, respectively, through a localization sequence outside the CDK-binding region. (wikipedia.org)
Enzyme8
- 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)
- 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)
- Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene . (wikipedia.org)
- Cell division protein kinase 8 is an enzyme that in humans is encoded by the CDK8 gene . (wikipedia.org)
- This association may interfere with PCNA-dependent enzyme activities involved in DNA synthesis [ 18 , 19 ]. (intechopen.com)
- Tat binding to TAR requires recruiting the enzyme cyclin-dependent kinase 9 (CDK-9) to the HIV promoter (where transcription begins). (bio-medicine.org)
- A highly selective inhibitor of a mitotic pathway enzyme polo-like kinase 1. (cyclacel.com)
Promoter2
- Exendin-4 stimulated cyclin A2 promoter activity via the cAMP-cAMP response element binding protein pathway. (diabetesjournals.org)
- This raised the possibility that HIV-1 gene expression in renal epithelium may also be critically dependent on CDK that control RNA polymerase II activity on the HIV-1 promoter ( 10 ). (asnjournals.org)
Complex6
- Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (wikipedia.org)
- Phosphorylation by CDK-activating kinase (CAK) at Thr 161 on the T-loop increases the complex activity. (wikipedia.org)
- Furthermore, cyclin binding determines the specificity of the cyclin-CDK complex for particular substrates. (wikipedia.org)
- First, its kinase activity is reversibly inhibited by formation of a complex with the 334 nt 7SK RNA, from which it is released under conditions of stress. (frontiersin.org)
- This protein forms a trimeric complex with cyclin H and MAT1 , which functions as a Cdk-activating kinase (CAK). (wikidoc.org)
- Data show that most mutations prevent formation of the cyclin-dependent kinase 12 (Cdk12)/cyclin K (CycK) complex, rendering the kinase inactive. (antibodies-online.com)
Activity7
- Thus, a timely block to CDK activity not only secures phase specificity of the cell cycle dependent HCMV IE gene expression program, but in addition plays a hitherto unrecognized role in preventing the establishment of a latent-like state. (prolekare.cz)
- Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. (wikipedia.org)
- The activity of this kinase is restricted to the G1-S phase, which is controlled by the regu. (genecards.org)
- Full kinase activity requires an activating phosphorylation on a threonine adjacent to the CDK's active site. (wikipedia.org)
- Shortly after its purification, P-TEFb was found to have protein kinase activity ( 50 ). (asm.org)
- With an unbiased kinase inhibitor screen, we identified Bohemine/Roscovitine, Gö6979 and JAK3 inhibitor VI as compounds that can efficiently decrease cysteine cathepsin activity. (pubmedcentralcanada.ca)
- This approach to understanding the relationship between HIV infection and kinase activity may introduce new drug targets to arrest HIV infectivity. (scirp.org)
20211
- Goldman Sachs 42nd Annual Global Healthcare Conference on Wednesday, June 9, 2021, at 11:20 a.m. (biospace.com)
Cdc22
- We have identified six protein kinases that belong to the family of cdc2-related kinases in Caenorhabditis elegans. (biologists.org)
- 1996 ) A Cdc2 dependent checkpoint maintains diploidy in Drosophila . (biologists.org)
Roscovitine1
- We previously reported that R-roscovitine (CYC202, seliciclib), a 2,6,9-trisubstituted purine analog, suppresses cyclin-dependent-kinase 2/cyclin E and inhibits ACTH in mice and zebrafish. (sigmaaldrich.com)
20011
- In addition to forming myelin sheaths to enhance nerve conduction velocity, OLs serve other important functions: they play a crucial role in organizing axonal voltage-dependent Na + and K + channels, induce a profound increase in myelinated axon diameter, help buffer K + ions released by axons, and provide neurotrophic support ( Baumann and Pham-Dinh, 2001 ). (jneurosci.org)
Polymerase II2
CDK51
- Protein kinases such as Cyclin-dependent kinase 5 (Cdk5) and c-Jun N-terminal kinases (JNKs) involve these steps. (frontiersin.org)