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

Cyclin C/CDK8 and cyclin H/CDK7/p36 are biochemically distinct CTD kinases. (1/122)

Phosphorylation of the carboxyl-terminal domain (CTD) of RNA polymerase II is important for basal transcriptional processes in vivo and for cell viability. Several kinases, including certain cyclin-dependent kinases, can phosphorylate this substrate in vitro. It has been proposed that differential CTD phosphorylation by different kinases may regulate distinct transcriptional processes. We have found that two of these kinases, cyclin C/CDK8 and cyclin H/CDK7/p36, can specifically phosphorylate distinct residues in recombinant CTD substrates. This difference in specificity may be largely due to their varying ability to phosphorylate lysine-substituted heptapeptide repeats within the CTD, since they phosphorylate the same residue in CTD consensus heptapeptide repeats. Furthermore, this substrate specificity is reflected in vivo where cyclin C/ CDK8 and cyclin H/CDK7/p36 can differentially phosphorylate an endogenous RNA polymerase II substrate. Several small-molecule kinase inhibitors have different specificities for these related kinases, indicating that these enzymes have diverse active-site conformations. These results suggest that cyclin C/CDK8 and cyclin H/CDK7/p36 are physically distinct enzymes that may have unique roles in transcriptional regulation mediated by their phosphorylation of specific sites on RNA polymerase II.  (+info)

GAL4 is regulated by the RNA polymerase II holoenzyme-associated cyclin-dependent protein kinase SRB10/CDK8. (2/122)

Phosphorylation of the yeast transcription factor GAL4 at S699 is required for efficient galactose-inducible transcription. We demonstrate that this site is a substrate for the RNA polymerase holoenzyme-associated CDK SRB10. S699 phosphorylation requires SRB10 in vivo, and this site is phosphorylated by purified SRB10/ SRB11 CDK/cyclin in vitro. RNA Pol II holoenzymes purified from WT yeast phosphorylate GAL4 at sites observed in vivo whereas holoenzymes from srb10 yeast are incapable of phosphorylating GAL4 at S699. Mutations at GAL4 S699 and srb10 are epistatic for GAL induction, demonstrating that SRB10 regulates GAL4 activity through this phosphorylation in vivo. These results demonstrate a function for the SRB10/ CDK8 holoenzyme-associated CDK that involves regulation of transactivators by phosphorylation during transcriptional activation.  (+info)

Transcription: Common cofactors and cooperative recruitment. (3/122)

Mammalian counterparts of the yeast SRB/MED transcriptional 'mediator' complex have recently been identified. These complexes define a common cofactor requirement for diverse transcriptional activators and underscore the conserved nature of the transcriptional machinery among eukaryotic organisms.  (+info)

Multiple signals regulate GAL transcription in yeast. (4/122)

Gal4p activates transcription of the Saccharomyces GAL genes in response to galactose and is phosphorylated during interaction with the RNA polymerase II (Pol II) holoenzyme. One phosphorylation at S699 is necessary for full GAL induction and is mediated by Srb10p/CDK8 of the RNA Pol II holoenzyme mediator subcomplex. Gal4p S699 phosphorylation is necessary for sensitive response to inducer, and its requirement for GAL induction can be abrogated by high concentrations of galactose in strains expressing wild-type GAL2 and GAL3. Gal4p S699 phosphorylation occurs independently of Gal3p and is responsible for the long-term adaptation response observed in gal3 yeast. SRB10 and GAL3 are shown to represent parallel mechanisms for GAL gene induction. These results demonstrate that Gal4p activity is controlled by two independent signals: one that acts through Gal3p-galactose and a second that is mediated by the holoenzyme-associated cyclin-dependent kinase Srb10p. Since Srb10p is regulated independently of galactose, our results suggest a function for CDK8 in coordinating responses to specific inducers with the environment through the phosphorylation of gene-specific activators.  (+info)

A regulatory shortcut between the Snf1 protein kinase and RNA polymerase II holoenzyme. (5/122)

RNA polymerase II holoenzymes respond to activators and repressors that are regulated by signaling pathways. Here we present evidence for a "shortcut" mechanism in which the Snf1 protein kinase of the glucose signaling pathway directly regulates transcription by the yeast holoenzyme. In response to glucose limitation, the Snf1 kinase stimulates transcription by holoenzyme that has been artificially recruited to a reporter by a LexA fusion to a holoenzyme component. We show that Snf1 interacts physically with the Srb/mediator proteins of the holoenzyme in both two-hybrid and coimmunoprecipitation assays. We also show that a catalytically hyperactive Snf1, when bound to a promoter as a LexA fusion protein, activates transcription in a glucose-regulated manner; moreover, this activation depends on the integrity of the Srb/mediator complex. These results suggest that direct regulatory interactions between signal transduction pathways and RNA polymerase II holoenzyme provide a mechanism for transcriptional control in response to important signals.  (+info)

Genetic analysis of the role of Pol II holoenzyme components in repression by the Cyc8-Tup1 corepressor in yeast. (6/122)

The Cyc8-Tup1 corepressor complex is targeted to promoters by pathway-specific DNA-binding repressors, thereby inhibiting the transcription of specific classes of genes. Genetic screens have identified mutations in a variety of Pol II holoenzyme components (Srb8, Srb9, Srb10, Srb11, Sin4, Rgr1, Rox3, and Hrs1) and in the N-terminal tails of histones H3 and H4 that weaken repression by Cyc8-Tup1. Here, we analyze the effect of individual and multiple mutations in many of these components on transcriptional repression of natural promoters that are regulated by Cyc8-Tup1. In all cases tested, individual mutations have a very modest effect on SUC2 RNA levels and no detectable effect on levels of ANB1, MFA2, and RNR2. Furthermore, multiple mutations within the Srb components, between Srbs and Sin4, and between Srbs and histone tails affect Cyc8-Tup1 repression to the same modest extent as the individual mutations. These results argue that the weak effects of the various mutations on repression by Cyc8-Tup1 are not due to redundancy among components of the Pol II machinery, and they argue against a simple redundancy between the holoenzyme and chromatin pathways. In addition, phenotypic analysis indicates that, although Srbs8-11 are indistinguishable with respect to Cyc8-Tup1 repression, the individual Srbs are functionally distinct in other respects. Genetic interactions among srb mutations imply that a balance between the activities of Srb8 + Srb10 and Srb11 is important for normal cell growth.  (+info)

Roles of transcription factor Mot3 and chromatin in repression of the hypoxic gene ANB1 in yeast. (7/122)

The hypoxic genes of Saccharomyces cerevisiae are repressed by a complex consisting of the aerobically expressed, sequence-specific DNA-binding protein Rox1 and the Tup1-Ssn6 general repressors. The regulatory region of one well-studied hypoxic gene, ANB1, is comprised of two operators, OpA and OpB, each of which has two strong Rox1 binding sites, yet OpA represses transcription almost 10 times more effectively than OpB. We show here that this difference is due to the presence of a Mot3 binding site in OpA. Mutations in this site reduced OpA repression to OpB levels, and the addition of a Mot3 binding site to OpB enhanced repression. Deletion of the mot3 gene also resulted in reduced repression of ANB1. Repression of two other hypoxic genes in which Mot3 sites were associated with Rox1 sites was reduced in the deletion strain, but other hypoxic genes were unaffected. In addition, the mot3Delta mutation caused a partial derepression of the Mig1-Tup1-Ssn6-repressed SUC2 gene, but not the alpha2-Mcm1-Tup1-Ssn6-repressed STE2 gene. The Mot3 protein was demonstrated to bind to the ANB1 OpA in vitro. Competition experiments indicated that there was no interaction between Rox1 and Mot3, indicating that Mot3 functions either in Tup1-Ssn6 recruitment or directly in repression. A great deal of evidence has accumulated suggesting that the Tup1-Ssn6 complex represses transcription through both nucleosome positioning and a direct interaction with the basal transcriptional machinery. We demonstrate here that under repressed conditions a nucleosome is positioned over the TATA box in the wild-type ANB1 promoter. This nucleosome was absent in cells carrying a rox1, tup1, or mot3 deletion, all of which cause some degree of derepression. Interestingly, however, this positioned nucleosome was also lost in a cell carrying a deletion of the N-terminal coding region of histone H4, yet ANB1 expression remained fully repressed. A similar deletion in the gene for histone H3, which had no effect on repression, had only a minor effect on the positioned nucleosome. These results indicate that the nucleosome phasing on the ANB1 promoter caused by the Rox1-Mot3-Tup1-Ssn6 complex is either completely redundant with a chromatin-independent repression mechanism or, less likely, plays no role in repression at all.  (+info)

Characterization of CAF4 and CAF16 reveals a functional connection between the CCR4-NOT complex and a subset of SRB proteins of the RNA polymerase II holoenzyme. (8/122)

The CCR4-NOT transcriptional regulatory complex affects transcription both positively and negatively and consists of the following two complexes: a core 1 x 10(6) dalton (1 MDa) complex consisting of CCR4, CAF1, and the five NOT proteins and a larger, less defined 1.9-MDa complex. We report here the identification of two new factors that associate with the CCR4-NOT proteins as follows: CAF4, a WD40-containing protein, and CAF16, a putative ABC ATPase. Whereas neither CAF4 nor CAF16 was part of the core CCR4-NOT complex, both CAF16 and CAF4 appeared to be present in the 1.9-MDa complex. CAF4 also displayed physical interactions with multiple CCR4-NOT components and with DBF2, a likely component of the 1.9-MDa complex. In addition, both CAF4 and CAF16 were found to interact in a CCR4-dependent manner with SRB9, a component of the SRB complex that is part of the yeast RNA polymerase II holoenzyme. The three related SRB proteins, SRB9, SRB10, and SRB11, were found to interact with and to coimmunoprecipitate DBF2, CAF4, CCR4, NOT2, and NOT1. Defects in SRB9 and SRB10 also affected processes at the ADH2 locus known to be controlled by components of the CCR4-NOT complex; an srb9 mutation was shown to reduce ADH2 derepression and either an srb9 or srb10 allele suppressed spt10-enhanced expression of ADH2. In addition, srb9 and srb10 alleles increased ADR1(c)-dependent ADH2 expression; not4 and not5 deletions are the only other known defects that elicit this phenotype. These results suggest a close physical and functional association between components of the CCR4-NOT complexes and the SRB9, -10, and -11 components of the holoenzyme.  (+info)

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1. Dannappel MV, Sooraj D, Loh JJ, Firestein R. Molecular and in vivo Functions of the CDK8 and CDK19 Kinase Modules. Front Cell Dev Biol. 2018;6:171 2. Borggrefe T, Yue X. Interactions between subunits of the Mediator complex with gene-specific transcription factors. Semin Cell Dev Biol. 2011;22:759-68 3. Putlyaev EV, Ibragimov AN, Lebedeva LA, Georgiev PG, Shidlovskii YV. Structure and Functions of the Mediator Complex. Biochemistry (Mosc). 2018;83:423-36 4. Poss ZC, Ebmeier CC, Taatjes DJ. The Mediator complex and transcription regulation. Crit Rev Biochem Mol Biol. 2013;48:575-608 5. Soutourina J. Transcription regulation by the Mediator complex. Nat Rev Mol Cell Biol. 2018;19:262-74 6. Roeder RG. Transcriptional regulation and the role of diverse coactivators in animal cells. FEBS letters. 2005;579:909-15 7. Schiano C, Casamassimi A, Vietri MT, Rienzo M, Napoli C. The roles of mediator complex in cardiovascular diseases. Biochim Biophys Acta. 2014;1839:444-51 8. Allen BL, Taatjes DJ. The ...
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Where is all this heading? Alongside the arms race of increasingly elaborate modelling software, there are also efforts to develop software that can assist in negotiation and mediation. Two decades ago Clara Ponsatí, a Spanish academic, came up with a clever idea while pondering the arduous Israeli-Palestinian peace process. As negotiators everywhere know, the first side to disclose all that it is willing to sacrifice (or pay) loses considerable bargaining power. Bereft of leverage, it can be pushed back to its bottom line by a clever opponent. But if neither side reveals the concessions it is prepared to make, negotiations can stall or collapse. In a paper published in 1992, Dr Ponsatí described how software could be designed to break the impasse. Difficult negotiations can often be nudged along by neutral mediators, especially if they are entrusted with the secret bottom lines of all parties. Dr Ponsatís idea was that if a human mediator was not trusted, affordable or available, a computer ...
MCM Proteins Are Associated with RNA Polymerase II Holoenzyme: MCMs are a family of proteins related to ATP-dependent helicases that bind to origin recognition
The CDK10/PISSLRE gene has been shown to encode two different CDK-like putative kinases. The function(s) of the gene products are unknown, although a role at the G2/M transition has been suggested. We characterised two novel cDNAs. CDK10 mRNA quantity was not found to be correlated with cell prolife …
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RNAPII can exist in two forms: RNAPII0, with a highly phosphorylated CTD, and RNAPIIA, with a nonphosphorylated CTD.[16] Phosphorylation occurs principally on Ser2 and Ser5 of the repeats, although these positions are not equivalent. The phosphorylation state changes as RNAPII progresses through the transcription cycle: The initiating RNAPII is form IIA, and the elongating enzyme is form II0. While RNAPII0 does consist of RNAPs with hyperphosphorylated CTDs, the pattern of phosphorylation on individual CTDs can vary due to differential phosphorylation of Ser2 versus Ser5 residues and/or to differential phosphorylation of repeats along the length of the CTD.[16] The PCTD (phosphoCTD of an RNAPII0) physically links pre-mRNA processing to transcription by tethering processing factors to elongating RNAPII, e.g., 5′-end capping, 3′-end cleavage, and polyadenylation.[16] Ser5 phosphorylation (Ser5PO4) near the 5′ ends of genes depends principally on the kinase activity of TFIIH (Kin28 in yeast; ...
Mouse anti Human Cdk6 antibody, clone DCS-83 recognizes the human cyclin dependent kinase 6, also known as Cdk6 or Serine/threonine-protei
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Tai unikalus informacijos apie Europoje pagamintas ir į ją importuotas chemines medžiagas šaltinis. Čia pateikiama informacija apie pavojingas cheminių medžiagų savybes, klasifikavimą, ženklinimą ir saugų jų naudojimą.. REACH. ...
EcR-dependent transcription, and thus, developmental timing in Drosophila, is regulated by CDK8 and its regulatory partner Cyclin C (CycC), and the level of CDK8 is affected by nutrient availability. cdk8 and cycC mutants resemble EcR mutants and EcR-target genes are systematically down-regulated in both mutants. Indeed, the ability of the EcR-Ultraspiracle (USP) heterodimer to bind to polytene chromosomes and the promoters of EcR target genes is also diminished. Mass spectrometry analysis of proteins that co-immunoprecipitate with EcR and USP identified multiple Mediator subunits, including CDK8 and CycC. Consistently, CDK8-CycC interacts with EcR-USP in vivo; in particular, CDK8 and Med14 can directly interact with the AF1 domain of EcR. These results suggest that CDK8-CycC may serve as transcriptional cofactors for EcR-dependent transcription. During the larval-pupal transition, the levels of CDK8 protein positively correlate with EcR and USP levels, but inversely correlate with the activity ...
As most subunits of the transcriptional mediator complex have not been functionally analyzed in vertebrates, the extent to which subunit composition may contribute to developmental mechanisms has remained unclear. Here, we present the first functional analysis of the subunit Crsp34 in the context of development and cell differentiation of zebrafish. We tested the concept of subunit-specific roles by analyzing the loss-of-function effects of three mediator subunits on the development of the vertebrate CNS: Trap100 (Pietsch et al. 2006), Crsp150 (Amsterdam et al. 2004), and Crsp34 (this study). As an experimental system we chose the developing zebrafish retina, since it represents one of the best-studied units of the CNS, regarding anatomy and control of proliferation, as well as expression of genes involved in patterning and differentiation for zebrafish (reviewed in Malicki 2000). Therefore, analysis of the retina in a mutant embryo allows us to detect developmental defects at high ...
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.
Complete information for MED7 gene (Protein Coding), Mediator Complex Subunit 7, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
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Martti Ahtisaari discusses his life and work as a worldwide peacemaker and the challenges that face peace negotiators in todays conflict zones. In summary, although all MED KO mice are embryonic lethal, they die at totally different developmental phases with distinctive phenotypes, suggesting important and particular roles for particular person Mediator subunits throughout growth. General, as a grasp coordinator, Mediator coordinates transcription and cell lineage specification/improvement to ensure that the correct genes are expressed at the right time and place and with the required intensity and period. Since a mediator is neutral, unhealthy information from the mediator is generally not met with the identical reactive devaluation as would greet that same dangerous news if damaged by a litigation adversary.. Following his/her appointment, the mediator will contact the parties or their counsel to repair a date for the holding of the primary assembly. Then again, Mediator can leverage Observer ...
Complete information for MED21 gene (Protein Coding), Mediator Complex Subunit 21, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
MED24 antibody (mediator complex subunit 24) for IHC-P, WB. Anti-MED24 pAb (GTX55701) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
MED31 antibody, N-term (mediator complex subunit 31) for WB, ChIP assay. Anti-MED31 pAb (GTX45020) is tested in Human samples. 100% Ab-Assurance.
Bourbon H-M., Aguilera A., Ansari AZ., Asturias FJ., Berk AJ., Bjorklund S., Blackwell TK., Borggrefe T., Carey M., Carlson M., Conaway JW., Conaway RC., Emmons SW., Fondell JD., Freedman LP., Fukasawa T., Gustafsson CM., Han M., He X., Herman PK., Hinnebusch AG., Holmberg S., Holstege FC., Jaehning JA., Kim Y-J., Kuras L., Leutz A., Lis JT., Meisterernest M., Naar AM., Nasmyth K., Parvin JD., Ptashne M., Reinberg D., Ronne H., Sadowski I., Sakurai H., Sipiczki M., Sternberg PW., Stillman DJ., Strich R., Struhl K., Svejstrup JQ., Tuck S., Winston F., Roeder RG., Kornberg RD ...
SCU22109 U22109 1948bp DNA PLN 26-APR-1995 Saccharomyces cerevisiae Ytp1p (YTP1) gene, complete cds. YTP1; Ytp1p. SCU22156 U22156 3680bp DNA PLN 26-APR-1995 Saccharomyces cerevisiae Hfm1p (HFM1) gene, complete cds. HFM1; Hfm1p. SCU22361 U22361 5599bp DNA PLN 26-APR-1995 Saccharomyces cerevisiae Rlr1p (RLR1) gene, complete cds. RLR1; Rlr1p. SCU23811 U23811 1494bp DNA PLN 26-APR-1995 Saccharomyces cerevisiae RNA polymerase II holoenzyme component (SRB7) gene, complete cds. SRB7; RNA polymerase II holoenzyme component. SCU23812 U23812 4849bp DNA PLN 26-APR-1995 Saccharomyces cerevisiae RNA polymerase II holoenzyme component (SRB9) gene, complete cds. SRB9; RNA polymerase II holoenzyme component. SCU24129 U24129 2965bp DNA PLN 26-APR-1995 Saccharomyces cerevisiae sporulation-specific septin (SPR3) gene, complete cds. SPR3; sporulation-specific septin. SCU24143 U24143 298bp mRNA PLN 26-APR-1995 Saccharomyces cerevisiae ribosomal protein S12 mRNA, partial cds. S12; ribosomal protein S12. SCU24144 ...
Human CDK7 (NM_001799, 1 a.a. - 346a.a.) and CCNH (NM_001239, 1 a.a. - 323 a.a.) and MNAT1 (NM_002431, 1 a.a. - 309 a.a.) recombinant protein with GST-His tag expressed in Sf9 cells. (P4662) - Products - Abnova
"CDK8 cyclin-dependent kinase 8 [Homo sapiens]". "CTDP1 CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) ... 2002). "A kinase-cyclin pair in the RNA polymerase II holoenzyme". Nature. 374 (6518): 193-6. doi:10.1038/374193a0. PMID ... TFIIH is a large protein complex that contains among others the CDK7/cyclin H kinase complex and a DNA helicase. TFIIH has ... Subsequent to the action of TFIIH kinase, Ser2 residues are phosphorylated by CTDK-I in yeast (CDK9 kinase in metazoans). Ctk1 ...
It was determined that he RV-cyclin bound to cyclin-dependent kinase 8 (CDK8) and increased its activity. The genes IEGs are ... Birkenheuer, C; Brewster, C; Quackenbush, S; Rovnak, J (2015). "Retroviral Cyclin Controls Cyclin-Dependent Kinase 8-Mediated ... "The retroviral cyclin of walleye dermal sarcoma virus binds cyclin-dependent kinases 3 and 8". Virology. 409 (2): 299-307. doi: ... The retroviral cyclin of walleye dermal sarcoma virus binds cylin-dependent kinases 3 and 8. Transgenic expression of walleye ...
... has been shown to interact with PPARGC1A, Cyclin-dependent kinase 8 and BRCA1. GRCh38: Ensembl release 89: ... 1999). "Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex". Nature. 398 (6730): 824-8. ... 2005). "The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent ... 23 (2): 620-8. doi:10.1128/MCB.23.2.620-628.2003. PMC 151539. PMID 12509459. Sato S, Tomomori-Sato C, Banks CA, et al. (2003 ...
... has been shown to interact with Estrogen receptor alpha, CEBPB and Cyclin-dependent kinase 8. GRCh38: Ensembl release 89 ... Stevens JL, Cantin GT, Wang G, Shevchenko A, Shevchenko A, Berk AJ (Apr 2002). "Transcription control by E1A and MAP kinase ... "Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex". Nature. 398 (6730): 824-8. Bibcode: ... 296 (5568): 755-8. Bibcode:2002Sci...296..755S. doi:10.1126/science.1068943. PMID 11934987. S2CID 19392260. Asada S, Choi Y, ...
... has been shown to interact with MED8, Cyclin-dependent kinase 8, POLR2A, MED12 and MED28. It also acts synergistically to ... 34 (8): 2219-29. doi:10.1093/nar/gkl239. PMC 1450333. PMID 16648364. Sato S, Tomomori-Sato C, Parmely TJ, Florens L, Zybailov B ... 275 (40): 31266-8. doi:10.1074/jbc.M002595200. PMID 10811649. Näär AM, Taatjes DJ, Zhai W, et al. (2002). "Human CRSP interacts ... 275 (40): 31266-8. doi:10.1074/jbc.M002595200. PMID 10811649. Ling Y, Smith AJ, Morgan GT (2006). "A sequence motif conserved ...
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/ ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ... "The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner". ...
... has been shown to interact with Estrogen receptor alpha, Cyclin-dependent kinase 8, Calcitriol receptor and BRCA1. GRCh38 ... "Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex". Nature. 398 (6730): 824-8. doi: ... "A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances VDR ... coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion". Proceedings of the National ...
... has been shown to interact with Thyroid hormone receptor alpha, Estrogen receptor alpha and Cyclin-dependent kinase 8. ... "Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex". Nature. 398 (6730): 824-8. Bibcode: ... 277 (45): 42852-8. doi:10.1074/jbc.M206061200. PMID 12218053. Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation ...
... has been shown to interact with: Cyclin-dependent kinase 8, Estrogen receptor alpha, MED21, and Thyroid hormone receptor ... "Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex". Nature. 398 (6730): 824-828. Bibcode ... 17 (8): 4622-32. doi:10.1128/MCB.17.8.4622. PMC 232315. PMID 9234719. Jiang YW, Veschambre P, Erdjument-Bromage H, Tempst P, ... doi:10.1016/S1097-2765(00)80131-8. PMID 9734358. Gu W, Malik S, Ito M, Yuan CX, Fondell JD, Zhang X, Martinez E, Qin J, Roeder ...
... has been shown to interact with PPARGC1A, Estrogen receptor alpha, STAT2, Cyclin-dependent kinase 8, Glucocorticoid ... 1999). "Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex". Nature. 398 (6730): 824-8. ... Malik, Sohail; Wallberg Annika E; Kang Yun Kyoung; Roeder Robert G (Aug 2002). "TRAP/SMCC/mediator-dependent transcriptional ... Malik S, Wallberg AE, Kang YK, Roeder RG (2002). "TRAP/SMCC/mediator-dependent transcriptional activation from DNA and ...
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 ...
Tassan, J P; Jaquenoud M; Léopold P; Schultz S J; Nigg E A (Sep 1995). "Identification of human cyclin-dependent kinase 8, a ... CCNC (gene) has been shown to interact with Estrogen receptor alpha and Cyclin-dependent kinase 8. GRCh38: Ensembl release 89: ... The encoded protein interacts with cyclin-dependent kinase 8 and induces the phosphorylation of the carboxy-terminal domain of ... 1995). "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. ...
Cyclin-dependent kinase 8 Estrogen receptor alpha, Gli3, G9a, PPARGC1A, MED26, SOX9, and Thyroid hormone receptor alpha. GRCh38 ... Zhou H, Kim S, Ishii S, Boyer TG (Dec 2006). "Mediator modulates Gli3-dependent Sonic hedgehog signaling". Molecular and ... "Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex". Nature. 398 (6730): 824-8. doi: ... "MED12 mutations link intellectual disability syndromes with dysregulated GLI3-dependent Sonic Hedgehog signaling". Proceedings ...
For example, DP00016 refers to the Cyclin-dependent kinase inhibitor 1 protein. Release 8 of DisProt contains more than 1400 ... Kovačević JJ (June 2012). "Computational analysis of position-dependent disorder content in DisProt database". Genomics ... DisProt 8 also introduced the concept of a stable DisProt region identifier. DisProt has been widely used to train software ...
... has been shown to interact with: Androgen receptor, BRCA1, Calcitriol receptor, Cyclin-dependent kinase 8, Estrogen ... Lee JW, Choi HS, Gyuris J, Brent R, Moore DD (1995). "Two classes of proteins dependent on either the presence or absence of ... Malik S, Wallberg AE, Kang YK, Roeder RG (August 2002). "TRAP/SMCC/mediator-dependent transcriptional activation from DNA and ... Frade R, Balbo M, Barel M (2002). "RB18A regulates p53-dependent apoptosis". Oncogene. 21 (6): 861-6. doi:10.1038/sj.onc. ...
... a cyclin-dependent kinase inhibitor, is dependent on p53 signaling". PLOS ONE. 8 (3): e59588. doi:10.1371/journal.pone.0059588 ... Fu W, Ma L, Chu B, Wang X, Bui MM, Gemmer J, Altiok S, Pledger WJ (Jun 2011). "The cyclin-dependent kinase inhibitor SCH 727965 ... Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. Dinaciclib ( ... Apoptosis of osteosarcoma cultures can be induced by the combination of the cyclin-dependent kinase inhibitor SCH727965 and a ...
cyclin 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 ...
The cyclin-dependent kinase inhibitor p21 is induced by both p53-dependent and p53-independent mechanisms and can arrest the ... ISBN 978-1-58829-500-2.[page needed] Gartel AL, Tyner AL (June 2002). "The role of the cyclin-dependent kinase inhibitor p21 in ... cell cycle at the G1/S and G2/M checkpoints by deactivating cyclin/cyclin-dependent kinase complexes. The SOS response is the ... In one of the earliest steps, the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), phosphorylates SIRT6 on ...
Activation loop Autophosphorylation Ca2+/calmodulin-dependent protein kinase Cell signaling Cyclin-dependent kinase G protein- ... the JAK kinases (a family of protein tyrosine kinases), and the PIP3-dependent kinase cascade were discovered. Kinases are ... Cyclin dependent kinases (CDKs) are a group of several different kinases involved in regulation of the cell cycle. They ... Harper, J. W.; Adams, P. D. (August 2001). "Cyclin-Dependent Kinases". Chemical Reviews. 101 (8): 2511-2526. doi:10.1021/ ...
... a cyclin-dependent kinase (Cdk) inhibitor, by Cdk including Pho85 kinase is required for its prompt degradation". Molecular ... "The yeast cyclin-dependent kinase inhibitor Sic1 and mammalian p27Kip1 are functional homologues with a structurally conserved ... "In CK2 inactivated cells the cyclin dependent kinase inhibitor Sic1 is involved in cell-cycle arrest before the onset of S ... "Cdc6 cooperates with Sic1 and Hct1 to inactivate mitotic cyclin-dependent kinases". Nature. 412 (6844): 355-8. Bibcode: ...
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 ...
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 D1, Cyclin O, Cyclin-dependent kinase 4, Cyclin-dependent kinase inhibitor 1C, DNMT1, EP300, Establishment of Sister ... "Association of proliferating cell nuclear antigen with cyclin-dependent kinases and cyclins in normal and transformed human T ... Xiong Y, Zhang H, Beach D (August 1993). "Subunit rearrangement of the cyclin-dependent kinases is associated with cellular ... Henneke G, Koundrioukoff S, Hübscher U (July 2003). "Phosphorylation of human Fen1 by cyclin-dependent kinase modulates its ...
... 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. ...
"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 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 ...
... 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 ...
"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 ...
... ; CDK5". omim.org. Retrieved 2020-11-02. Tsai, Li-Huei. Cyclin Dependent Kinase 5 (Cdk5). Bibb JA ( ... membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase". The Journal of Neuroscience. 23 (12): ... The molecule belongs to the cyclin-dependent kinase family. Kinases are enzymes that catalyze reactions of phosphorylation, a ... Cyclin dependent kinase 5 is a protein, and more specifically an enzyme, that is encoded by the Cdk5 gene. It was discovered 15 ...
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.[ ...
Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which ... Simone C, Giordano A (2007). "Abrogation of signal-dependent activation of the cdk9/cyclin T2a complex in human RD ... This cyclin and its kinase partner CDK9 were found to be subunits of the transcription elongation factor p-TEFb. The p-TEFb ... "MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner". Mol. Cell. Biol. 23 (14): 4859-69 ...
The cell cycle is regulated by a series of signalling factors and complexes such as cyclin-dependent kinases and p53, to name a ... have allowed scientists to get a better idea of the structure of cells.[8] ...
... , NCK5AI, P39, p39nck5ai, cyclin-dependent kinase 5, regulatory subunit 2 (p39), cyclin dependent kinase 5 regulatory ... cyclin-dependent protein kinase 5 activator activity. • lipid binding. Cellular component. • cytoplasm. • cyclin-dependent ... 2002). "The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent ... positive regulation of protein kinase activity. • regulation of cyclin-dependent protein serine/threonine kinase activity. • ...
Cell cycle progression is controlled by ordered action of cyclin-dependent kinases (CDKs), activated by specific cyclins that ... is one of the 19S subcomponents that also tightly binds the cyclin-dependent kinase CDK4 and plays a key role in recognizing ... In particular, exit from mitosis requires the proteasome-dependent dissociation of the regulatory component cyclin B from the ... the ATP-dependent proteolytic complex that was responsible for ubiquitin-dependent protein degradation was discovered and was ...
"Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational ... 9 (8): 689-710. doi:10.1101/gr.9.8.689. PMID 10447505.. *^ Airas RK (December 2007). "Magnesium dependence of the measured ... 280 (4): 2405-8. doi:10.1074/jbc.C400431200. PMID 15579907.. *^ Kawahara A, Stainier DY (August 2009). "Noncanonical activity ... Class II synthetases have two or three (more frequently three) Mg2+ ions, while class I only requires one Mg2+ ion.[7][8] ...
... preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase ... InChI=1S/C10H18O/c1-5-10(4,11)8-6-7-9(2)3/h5,7,11H,1,6,8H2,2-4H3 ... 8]. Zastosowanie[edytuj , edytuj kod]. Ma szerokie zastosowanie ...
All these phases in the cell cycle are highly regulated by cyclins, cyclin-dependent kinases, and other cell cycle proteins. ... Generation of pressure is dependent on formin-mediated F-actin nucleation[71] and Rho kinase (ROCK)-mediated myosin II ... This can occur when cells become overcrowded (density-dependent inhibition) or when they differentiate to carry out specific ... Ramanathan SP, Helenius J, Stewart MP, Cattin CJ, Hyman AA, Muller DJ (February 2015). "Cdk1-dependent mitotic enrichment of ...
"Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation". Nature Neuroscience. 10 ( ... Src kinase enhances NMDA receptor currents.[98]. *Na+, K+ and Ca2+ not only pass through the NMDA receptor channel but also ... "MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term ... Depolarization of the cell dislodges and repels the Mg2+ and Zn2+ ions from the pore, thus allowing a voltage-dependent flow of ...
... endothelin receptor A and cyclin dependent kinase inhibitor. Mutations in interleukin 6 may be protective.[citation needed]. ... 243 (2): 500-8. doi:10.1148/radiol.2431060006. PMID 17293572.. *^ Raymond, J; Guilbert, F; Weill, A; Georganos, SA; Juravsky, L ... and a rate of rebleeding 8 times higher than surgically-clipped aneurysms.[24] ...
"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 ... Lodish, Harvey F. (২০০০)। Molecular cell biology। Internet Archive। New York : W.H. Freeman। আইএসবিএন 978-0-7167-3136-8।. ...
... phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase" ... "Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV transcription by a Tat-dependent mechanism". J. Immunol. 169 ... A dose-dependent response was not observed, raising questions about the robustness of the findings.[21] ... of cellular CDK9 and cyclin T1, and hence increases the production of full-length viral RNA.[8] ...
"CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle progression". Cell. 151 (6): 1308-18. doi: ... "The turn motif is a phosphorylation switch that regulates the binding of Hsp70 to protein kinase C". The Journal of Biological ... 2 (8): 469-75. doi:10.1038/35019501. PMID 10934466.. *^ Gupta S, Deepti A, Deegan S, Lisbona F, Hetz C, Samali A (July 2010). ... The protein is then free to fold on its own, or to be transferred to other chaperones for further processing.[8] HOP (the Hsp70 ...
Jiang MC, Liao CF, Tai CC (June 2002). "CAS/CSE 1 stimulates E-cadhrin-dependent cell polarity in HT-29 human colon epithelial ... "Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes". The Journal of Cell Biology. 128 (5): ... Laoukili J, Alvarez-Fernandez M, Stahl M, Medema RH (September 2008). "FoxM1 is degraded at mitotic exit in a Cdh1-dependent ... The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein composed of five extracellular cadherin repeats, a ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... 1omw: Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and ... Buhl AM, Osawa S, Johnson GL (1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human ... 2bcj: Crystal Structure of G Protein-Coupled Receptor Kinase 2 in Complex with Galpha-q and Gbetagamma Subunits ...
Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bad (a Bcl-2 ... Caspases are proteins that are highly conserved, cysteine-dependent aspartate-specific proteases. There are two types of ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... the protein is cleaved by a calcium-dependent calpain protease ... "Apoptosis induced by Oropouche virus infection in HeLa cells is dependent on virus protein expression". Virus Research. 149 (1 ...
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 ...
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 ...
GTP-dependent protein binding. • GTPase activity. • mitogen-activated protein kinase kinase kinase binding. • protein binding. ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... "The MAP kinase kinase kinase MLK2 co-localizes with activated ... protein kinase binding. • nucleotide binding. • GTP binding. • identical protein binding. Cellular component. • cytoplasm. • ... regulation of protein kinase activity. • regulation of attachment of spindle microtubules to kinetochore. • regulation of small ...
Cyclin-dependent kinases (CDKs) 4 and 6 are enzymes that have been shown to promote cell division and multiplication in both ... Ribociclib, sold under the brand name Kisqali,[1] is an inhibitor of cyclin D1/CDK4 and CDK6, and is used for the treatment of ... This page was last edited on 8 March 2021, at 13:06 (UTC). ... 8] In the clinical trial relevant for the drug's approval, ...
... 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 ... Biophys. (UNITED STATES) 355 (2): 241-8. ISSN 0003-9861. PMID 9675033. doi:10.1006/abbi.1998.0720. ...
... cyclins and cyclin dependent kinases". Oncogene. 15 (2): 143-57. doi:10.1038/sj.onc.1201252. PMID 9244350.. ... "BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site". Mol. Cell. Biol. 19 (7): ... "BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3". ... kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment ...
Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P (March 2001). "Amphiphysin 1 binds the cyclin-dependent kinase ... Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P (March 2001). "Amphiphysin 1 binds the cyclin-dependent kinase ... Chen-Hwang MC, Chen HR, Elzinga M, Hwang YW (May 2002). "Dynamin is a minibrain kinase/dual specificity Yak1-related kinase 1A ... Micheva KD, Ramjaun AR, Kay BK, McPherson PS (September 1997). "SH3 domain-dependent interactions of endophilin with ...
... phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase ... Kematian akibat AIDS di Indonesia masih tinggi, karena hanya 8 persen Orang Dengan HIV AIDS (ODHA) yang mendapatkan pengobatan ... HIV-2 memiliki 8 jenis subtipe yang diduga berasal dari Sooty mangabey yang berbeda-beda.[10] ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... Gαs activates the cAMP-dependent pathway by stimulating the production of cyclic AMP (cAMP) from ATP. This is accomplished by ... The cAMP-dependent pathway is used as a signal transduction pathway for many hormones including:. *ADH - Promotes water ... cAMP can then act as a second messenger that goes on to interact with and activate protein kinase A (PKA). PKA can ...
These transitions are controlled by the cyclin-dependent kinase Cdk1.[6] Though the proteins that control Cdk1 are well ... a cyclin-dependent kinase, on a tyrosine residue. Cdc2 drives entry into mitosis by phosphorylating a wide range of targets. ... The protein kinase Cdr2 (which negatively regulates Wee1) and the Cdr2-related kinase Cdr1 (which directly phosphorylates and ... Wu L, Russell P (June 1993). "Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase". Nature. 363 (6431): 738-41. ...
The process follows fertilization, with the transfer being triggered by the activation of a cyclin-dependent kinase complex.[1] ... high levels of proteins that control cell cycle progression such as the cyclins and their associated cyclin-dependent kinases ( ... cdk). The complex Cyclin B/CDK1 a.k.a. MPF (maturation promoting factor) promotes entry into mitosis. ... This larger cell is specified as the D macromere.[8][9] Unlike equally cleaving spiralians, the D macromere is specified at the ...
protein serine/threonine kinase activity. • cyclin-dependent protein serine/threonine kinase activity. ... The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate ... "Entrez Gene: CDK8 cyclin-dependent kinase 8".. *^ Nemet J, Jelicic B, Rubelj I, Sopta M (Feb 2014). "The two faces of Cdk8, a ... Rickert P, Corden JL, Lees E (Jan 1999). "Cyclin C/CDK8 and cyclin H/CDK7/p36 are biochemically distinct CTD kinases". Oncogene ...
... a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a ... cyclin-dependent protein serine/threonine kinase activity Source: GO_Central. *RNA polymerase II carboxy-terminal domain kinase ... IPR011009. Kinase-like_dom_sf. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. IPR008271. Ser/Thr_kinase_AS. ... IPR011009. Kinase-like_dom_sf. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. IPR008271. Ser/Thr_kinase_AS. ...
RV-cyclin), encoded by WDSV, has separable cyclin box and transcription activation domains. It binds to cyclin-dependent kinase ... Retroviral cyclin controls cyclin-dependent kinase 8-mediated transcription elongation and reinitiation.. [Claire H Birkenheuer ... The retroviral cyclin (RV-cyclin) represents a highly selected probe of CDK8 function. RV-cyclin does not control CDK8 ... RV-cyclin does not increase activating phosphorylation events in the mitogen-activated protein kinase pathway and does not ...
Expression of Cyclin-Dependent Kinase 6, but not Cyclin-Dependent Kinase 4, Alters Morphology of Cultured Mouse Astrocytes. Mol ... Elevated activity of cyclin-dependent kinase 6 (cdk6), a pRB kinase, was detected in all five squamous cell carcinoma lines. ... Elevated activity of cyclin-dependent kinase 6 in human squamous cell carcinoma lines. S Timmermann, PW Hinds and K Munger ... Cyclin-Dependent Kinase 6 Inhibits Proliferation of Human Mammary Epithelial Cells. Mol. Cancer Res., February 1, 2004; 2(2): ...
... y1 sc v1 VALIUM22 Cyclin-dependent kinase 8 shRNA plasmid is an eagle-i resource of type shRNA plasmid at Harvard University. ... VALIUM22 Cyclin-dependent kinase 8 shRNA plasmid. eagle-i ID. http://harvard.eagle-i.net/i/0000012e-53ff-259e-550e-f59280000000 ...
Cyclin-dependent kinase 8,Mediator complex subunit CDK8,Mediator of RNA polymerase II transcription subunit CDK8,Mouse,Mus ... Cyclin-dependent kinase 8,Mediator complex subunit CDK8,Mediator of RNA polymerase II transcription subunit CDK8,Mouse,Mus ... Cyclin-dependent kinase 8,Mediator complex subunit CDK8,Mediator of RNA polymerase II transcription subunit CDK8,Mouse,Mus ... Cyclin-dependent kinase 8,Mediator complex subunit CDK8,Mediator of RNA polymerase II transcription subunit CDK8,Mouse,Mus ...
Cyclin Dependent Kinase 8, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human ... protein serine/threonine kinase activity. TAS. --. GO:0004693. cyclin-dependent protein serine/threonine kinase activity. IBA. ... This kinase regulates transcription by targeting the cyclin-dependent kinase 7 subunits of the general transcription initiation ... Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C. (PMID: 7568034) Tassan JP … ...
Here we report the identification of a human protein kinase, K35 [cyclin-dependent kinase 8 (CDK8)], that is likely to be a ... Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C. Proceedings of the National ... Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C ... The K35-cyclin C complex is structurally related to SRB10-SRB11, a CDK-cyclin pair recently shown to be part of the RNA ...
... of cyclin dependent kinase 8 (CDK8) revealed that miR-107 directly targets CDK8. The expression level of CDK8 mRNA and protein ... Feng L, Xie Y, Zhang H: Wu Y: miR-107 targets cyclin-dependent kinase 6 expression, induces cell cycle G1 arrest and inhibits ... Cyclin dependent kinase 8 (CDK8) locating on chromosome13q12 has five transcripts and only one transcript encodes protein ... Sharma PS, Sharma R, Tyagi R: Inhibitors of cyclin dependent kinases: useful targets for cancer treatment. Curr Cancer Drug ...
"CDK8 cyclin-dependent kinase 8 [Homo sapiens]".. *^ "CTDP1 CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) ... 2002). "A kinase-cyclin pair in the RNA polymerase II holoenzyme". Nature. 374 (6518): 193-6. doi:10.1038/374193a0. PMID ... TFIIH is a large protein complex that contains among others the CDK7/cyclin H kinase complex and a DNA helicase. TFIIH has ... Also involved in the phosphorylation and regulation of the RPB1 CTD is cyclin T1 (CCNT1).[19] Cyclin T1 tightly associates and ...
Cyclin-dependent kinase 8. A. 405. Homo sapiens. Mutation(s): 0 Gene Names: CDK8. EC: 2.7.11.22 (PDB Primary Data), 2.7.11.23 ( ... Here, we present a structure-kinetic relationship study of the cyclin-dependent kinase 8 (CDK8)/cyclin C (CycC) complex ... ... Here, we present a structure-kinetic relationship study of the cyclin-dependent kinase 8 (CDK8)/cyclin C (CycC) complex. The ... Cyclin-C. B. 287. Homo sapiens. Mutation(s): 0 Gene Names: CCNC. ... Hydrogen bonding with the kinase hinge region contributes to ...
Cyclin-Dependent Kinases / metabolism * DNA-Binding Proteins / metabolism * Gene Expression Regulation, Fungal / physiology* ... Cyclin-Dependent Kinase 8 * ...
To investigate the expression of cyclin-dependent kinase 8 (CDK8) and β-catenin in colon cancer and evaluate the role of CDK8 ... Cyclin-dependent kinase (CDK) 8 is located in chromosome 13q12.13 and is a member of the CDK family [5, 6]. CDK is classified ... Differential expression of G 1 cyclins and cyclin-dependent kinase inhibitors in normal and transformed melanocytes. Invest ... Effects of cyclin-dependent kinase 8 specific siRNA on the proliferation and apoptosis of colon cancer cells. ...
"Entrez Gene: CDK4 cyclin-dependent kinase 4". "CDK4 - Cyclin-dependent kinase 4 - Homo sapiens (Human) - CDK4 gene & protein". ... "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 ... Kato JY; Matsuoka M; Strom DK; Sherr CJ (1994). "Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase". ...
Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities Donald C. Porter, Elena Farmaki, ... Tumor suppressor Hippo/MST1 kinase mediates chemotaxis by regulating spreading and adhesion Yulia Artemenko, Petros Batsios, ... Identification of an N-terminal inhibitory extension as the primary mechanosensory regulator of twitchin kinase Eleonore von ... SAMBA, a plant-specific anaphase-promoting complex/cyclosome regulator is involved in early development and A-type cyclin ...
mTORC1 Down-Regulates Cyclin-Dependent Kinase 8 (CDK8) and Cyclin C (CycC). ... expression through activation of protein kinase B and mitogen-activated protein kinase kinase pathways. ... Insulin-Dependent Regulation of mTORC2-Akt-FoxO Suppresses TLR4 Signaling in Human Leukocytes: Relevance to Type 2 Diabetes. ... TLR4-mediated AKT activation is MyD88/TRIF dependent and critical for induction of oxidative phosphorylation and mitochondrial ...
Cyclin Dependent Kinase 5, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human ... protein serine/threonine kinase activity. TAS. --. GO:0004693. cyclin-dependent protein serine/threonine kinase activity. TAS. ... Cdks (cyclin-dependent kinases) are heteromeric serine/threonine kinases that control progression through the cell cycle in ... This gene encodes a proline-directed serine/threonine kinase that is a member of the cyclin-dependent kinase family of proteins ...
Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities.. Porter DC, Farmaki E, Altilia S ... Mediator kinase CDK8/CDK19 drives YAP1-dependent BMP4-induced EMT in cancer. ... Inhibition of CDK8 mediator kinase suppresses estrogen dependent transcription and the growth of estrogen receptor positive ... CDK8/19 Mediator kinases potentiate induction of transcription by NFκB.. Chen M, Liang J, Ji H, Yang Z, Altilia S, Hu B, ...
In this study, we isolated the cyclin-dependent kinase 8 (TaCDK8) from wheat cultivar Jing411 and found that silencing of ... 0 (Aldehydes); 0 (Plant Proteins); EC 2.7.11.22 (Cyclin-Dependent Kinase 8). ... In addition, compound 17-28 blocked 4-HNE-induced apoptosis of ARPE-19 cells in a concentration-dependent manner. The results ... to stimulate the TaWIN1-dependent transcription. Bgt conidia on the leaves of TaWIN1-silenced plants also showed reduced ...
cyclin-dependent kinase 8 * Species. H. sapiens (human) * Insert Size (bp). 1395 ...
Cyclin-Dependent Kinase 8 (CDK8) Antikörper Synonyme für dieses Antigen anzeigen * K35 ... Cyclin-dependent kinase 8, RGD1560888, CDK8 protein kinase, K35, Mediator complex subunit CDK8, Protein kinase K35 ... Region between residue 420 and 470 of human cyclindependent kinase 8 using the numbering given in entry NP_001251.1 (GeneID ... Family: Protein Kinase. Synonyms: CDK8, Cell division protein kinase 8, ...
A good example of an oncogene is CDK8: Cyclin-dependent kinase 8. Misregulated CDK8 is an important factor in the development ... By way of explanation: CDK8 is a so-called kinase, i.e. it modifies various target molecules with phosphate groups that are ... "Conversely, this means that all future attempts to inhibit CDK8 must at least focus on triple complexes of CDK8, Cyclin C and ... If, as has happened in the past, inhibitors are developed only against CDK8 in complex with Cyclin C, the resulting compounds ...
... cyclin-dependent kinase 8) for ICC/IF, IP, WB. Anti-CDK8 pAb (GTX22955) is tested in Human, Mouse, Rat samples. 100% Ab- ... cyclin-dependent kinase 8. Background. A family of proteins designated as cdks are critical regulators of cell cycle ... Immunofluorescence: assay dependent. Immunoprecipitation (with protein A, native): use at a concentration of 10μg / mg of ... The p54 / Cdk 8 interacts exclusively with Cyclin C. The Cdk 8 Cyclin C complex activates the kinase. Because of analogy with ...
cyclin-dependent kinase 9 (cdc2-related kinase). Cdkn1a 12575. cyclin-dependent kinase inhibitor 1a (p21). ... cyclin-dependent kinase 8. Cdk9 107951. ... cyclin-dependent kinase inhibitor 2a. Cebpb 12608. ccaat/ ...
Correction for Szilagyi et al., "Cyclin-Dependent Kinase 8 Regulates Mitotic Commitment in Fission Yeast" Zsolt Szilagyi, Gabor ... Correction for Xu and Davis, "c-Jun NH2-Terminal Kinase Is Required for Lineage-Specific Differentiation but Not Stem Cell Self ...
Cyclin-Dependent Kinase 8/genetics*. *RNA Polymerase II/chemistry/genetics*. *RNA, Messenger/genetics* ... Focusing on CTD-length dependent genes, we observed Cdk8 occupancy at the promoters of genes with increased mRNA levels in the ... Focusing on CTD-length dependent genes, we observed Cdk8 occupancy at the promoters of genes with increased mRNA levels in the ...
Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors. Thomas A. Milne, Christina M. Hughes, ... Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors. Thomas A. Milne, Christina M. Hughes, ... Here, we show that menin directly regulates expression of the cyclin-dependent kinase inhibitors p27Kip1 and p18Ink4c . Menin ... Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors Message Subject (Your Name) has sent you ...
It works by inhibiting cyclin-dependent kinases, arresting cell division and causing apoptosis in non-small lung cancer cells. ... Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex ... Cyclin-dependent protein serine/threonine kinase regulator activity. Specific Function. Ser/Thr-kinase component of cyclin D- ... Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the .... Gene Name. CDK7. Uniprot ID. ...
  • Cell division protein kinase 8 is an enzyme that in humans is encoded by the CDK8 gene . (wikipedia.org)
  • CDK8 and cyclin C associate with the mediator complex and regulate transcription by several mechanisms. (wikipedia.org)
  • It binds to cyclin-dependent kinase 8 (CDK8) and enhances its kinase activity. (sigmaaldrich.com)
  • The RV-cyclin increases CDK8 occupancy at the EGR1 gene locus before and after serum stimulation. (sigmaaldrich.com)
  • The retroviral cyclin (RV-cyclin) represents a highly selected probe of CDK8 function. (sigmaaldrich.com)
  • RV-cyclin does not control CDK8 specificity but instead enhances CDK8's effects on regulated genes, an important distinction for its use to delineate natural CDK8 targets. (sigmaaldrich.com)
  • Cdk8,Cell division protein kinase 8,Cyclin-dependent kinase 8,Mediator complex subunit CDK8,Mediator of RNA polymerase II transcription subunit CDK8,Mouse,Mus musculus rna research rna is not so stable and very sticky. (antibody-antibodies.com)
  • CDK8 (Cyclin Dependent Kinase 8) is a Protein Coding gene. (genecards.org)
  • Here we report the identification of a human protein kinase, K35 [cyclin-dependent kinase 8 (CDK8)], that is likely to be a physiological partner of cyclin C. A specific interaction between K35 and cyclin C could be demonstrated after translation of CDKs and cyclins in vitro. (unibas.ch)
  • Hence, we propose that human K35(CDK8)-cyclin C might be functionally associated with the mammalian transcription apparatus, perhaps involved in relaying growth-regulatory signals. (unibas.ch)
  • Luciferase assays using a reporter carrying a putative miR-107 target site in the 3′untranslated region (3′-UTR) of cyclin dependent kinase 8 (CDK8) revealed that miR-107 directly targets CDK8. (biomedcentral.com)
  • Cyclin dependent kinase 8 (CDK8) locating on chromosome13q12 has five transcripts and only one transcript encodes protein product containing 464 amino acid residues (molecular weight 53.2 kD). (biomedcentral.com)
  • To investigate the expression of cyclin-dependent kinase 8 (CDK8) and β-catenin in colon cancer and evaluate the role of CDK8 in the proliferation, apoptosis and cell cycle progression of colon cancer cells, especially in HCT116 cell line. (biomedcentral.com)
  • Mediator kinase CDK8/CDK19 drives YAP1-dependent BMP4-induced EMT in cancer. (nih.gov)
  • CDK8/19 Mediator kinases potentiate induction of transcription by NFκB. (nih.gov)
  • Inhibition of CDK8 mediator kinase suppresses estrogen dependent transcription and the growth of estrogen receptor positive breast cancer. (nih.gov)
  • A good example of an oncogene is CDK8: Cyclin-dependent kinase 8. (uni-bayreuth.de)
  • Using structural biochemistry - coupled with systems biology - the research team deciphered how CDK8 is activated by two of the three partners, Cyclin C and MED12. (uni-bayreuth.de)
  • By way of explanation: CDK8 is a so-called kinase, i.e. it modifies various target molecules with phosphate groups that are important for the cell's gene reading machinery). (uni-bayreuth.de)
  • As Dr. Claus-D. Kuhn's research group was able to show, this structural change leads to a situation in which so-called type II kinase inhibitors no longer bind effectively to CDK8 and inhibit it. (uni-bayreuth.de)
  • Conversely, this means that all future attempts to inhibit CDK8 must at least focus on triple complexes of CDK8, Cyclin C and MED12. (uni-bayreuth.de)
  • If, as has happened in the past, inhibitors are developed only against CDK8 in complex with Cyclin C, the resulting compounds are very likely ineffective against CDK8 in human cells", concludes Dr. Claus-D. Kuhn. (uni-bayreuth.de)
  • Focusing on CTD-length dependent genes, we observed Cdk8 occupancy at the promoters of genes with increased mRNA levels in the rpb1-CTD11 mutant (Figure 8A), while very little Cdk8 was observed at the set of genes with decreased levels (data not shown). (nih.gov)
  • For instance, CDK7, CDK8, and CDK9 contribute to the regulation of RNA polymerase II and the control of cellular transcription ( 8 , 9 ). (aacrjournals.org)
  • CDK8 kinase activity was necessary for beta-catenin-driven transformation and for expression of several beta-catenin transcriptional targets. (nih.gov)
  • SEL120-34A is a novel inhibitor of Cyclin- dependent kinase 8 (CDK8), which regulates transcription by associating with the Mediator complex. (aacrjournals.org)
  • Further studies on a large panels of responder and non-responder cell lines identified robust biomarkers which could be used with high confidence for stratification and personalized approach in CDK8-dependent AML cases. (aacrjournals.org)
  • Selvita has discovered and is developing SEL120, a therapy that targets the cyclin-dependent kinase 8 (CDK8) protein, which plays a unique and critical role in gene regulation. (centerwatch.com)
  • SEL120 is an ATP-competitive and selective inhibitor of CDK8 and a closely related serine kinase, CDK19. (centerwatch.com)
  • Here, we show that Mediator's dissociable cyclin dependent kinase 8 (CDK8) module (CKM), consisting of cdk-8 , cic-1 /Cyclin C , mdt-12 / dpy-22 , and mdt-13 / let-19 , is required to inhibit ectopic vulval cell fates downstream of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. (genetics.org)
  • It is regulated by Cyclin D. Ribociclib are US FDA approved CDK4 and CDK6 inhibitors for the treatment of estrogen receptor positive/ HER2 negative advanced breast cancer. (wikipedia.org)
  • Here, we show that menin directly regulates expression of the cyclin-dependent kinase inhibitors p27 Kip1 and p18 Ink4c . (pnas.org)
  • However, due to the high degree of structural homology within the CDK protein family, putative small-molecule CDK inhibitors may exert their effects through combinatorial inhibition of multiple CDKs and other closely related serine/threonine kinases. (aacrjournals.org)
  • Synthesis and Evaluation of Indenopyrazoles as Cyclin-Dependent Kinase Inhibitors. (rcsb.org)
  • New indeno[1,2-c]pyrazol-4-one cyclin dependent kinase inhibitors have been disclosed. (rcsb.org)
  • 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)
  • Conversely, the structures of the inactive states of kinase-family members can vary widely from each other, a principle that can be exploited to improve the specificity of kinase inhibitors. (springer.com)
  • Targeting the cell division cycle in cancer: CDK and cell cycle checkpoint kinase inhibitors. (springer.com)
  • At the molecular level, production and association of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CKIs) regulate cycle progression. (jneurosci.org)
  • Cycle progression is controlled by pro-mitogenic cyclin-dependent kinases (CDKs) complexed with regulatory cyclins, and anti-mitogenic CDK inhibitors (CKIs). (jneurosci.org)
  • The activity of CDK6 is very tightly controlled by association with D-cyclins ( 7 ) and two families of CDK inhibitors, including the CIP/KIP family and the inhibitors of CDK4 (INK4) family proteins ( 9 ). (aacrjournals.org)
  • Inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinases, such as erlotinib and gefitinib, have not been very effective in the treatment of breast cancer although many breast cancer cells express EGFR. (aacrjournals.org)
  • Background -The cyclin-dependent kinase inhibitors (CKIs) have different patterns of expression in vascular diseases. (ahajournals.org)
  • Conclusions -p27 Kip1 and p21 Cip1 are potent inhibitors of VSMC growth compared with p16 Ink4 because of their different molecular mechanisms of cyclin-dependent kinase inhibition in the G 1 phase of the cell cycle. (ahajournals.org)
  • 2 Cyclin-dependent kinase inhibitors (CKIs) are naturally occurring gene products that inhibit the cyclin-CDK activity leading to G 1 arrest. (ahajournals.org)
  • Cyclin-dependent kinases (CDKs) have been considered promising drug targets for a number of years, but most CDK inhibitors have failed rigorous clinical testing. (aspetjournals.org)
  • Indeed, the only nuclear G1/S molecules are the cell cycle inhibitors, pRb, p57, and variably, p21: none of the cyclins or cdks necessary to drive human β-cell proliferation are present in the nuclear compartment. (diabetesjournals.org)
  • Cooperativity between orthosteric inhibitors and allosteric inhibitor 8-anilino-1-naphthalene sulfonic acid (ANS) in cyclin-dependent kinase 2 (Cdk2). (umn.edu)
  • This includes members of the pRb family of pocket proteins, as well as cyclins and cyclin-dependent kinase inhibitors, among many others ( 8 ). (asm.org)
  • Resistance to BRAFV600E inhibitors is associated with reactivation of mitogen-activated protein kinase (MAPK) signaling at different levels in melanoma. (harvard.edu)
  • 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)
  • Furthermore, a nuclear Smad complex that includes Smad3 and the transcription factor Sp1 is thought to mediate transcription of the cyclin-dependent kinase (CDK) inhibitors p15 and p21, whose promoters contain an Sp1-binding site ( 8 , 9 ). (aacrjournals.org)
  • Palbociclib is an investigational oral targeted agent that selectively inhibits cyclin-dependent kinases (CDKs) 4 and 6 to regain cell cycle control and block tumor cell proliferation. (thestreet.com)
  • 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)
  • 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)
  • CDK is classified as a serine-threonine protein kinase, and ten of its members have been identified in the CDK family so far, where these members have some homology to a certain extent. (biomedcentral.com)
  • This gene encodes a proline-directed serine/threonine kinase that is a member of the cyclin-dependent kinase family of proteins. (genecards.org)
  • Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. (genecards.org)
  • Serine/threonine-protein kinase involved in the control of the eukaryotic cell cycle, whose activity is controlled by an associated cyclin. (uniprot.org)
  • The transforming growth factor β (TGFβ) superfamily consists of a large group of secreted polypeptide growth factors that bind transmembrane serine-threonine kinase receptor complexes ( 1 , 2 ). (aacrjournals.org)
  • Cyclin-dependent kinases (CDK) are serine/threonine kinases that are activated upon association with cyclin proteins to form CDK complexes. (aacrjournals.org)
  • Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase structurally homologous to the Cdk family members which modulate the cell cycle. (frontiersin.org)
  • RV-cyclin does not increase activating phosphorylation events in the mitogen-activated protein kinase pathway and does not inhibit decay of IEG mRNAs. (sigmaaldrich.com)
  • As one example, we have only recently learned that loss of the platelet-derived growth factor (PDGF) receptor-α in adult human β-cells, with the resultant loss of ability to activate mitogen-activated protein kinase and methylation (Ezh2) and downstream cell cycle (p16) machinery, may underlie the refractoriness of human β-cells to proliferation ( 16 ). (diabetesjournals.org)
  • This kinase and its regulatory subunit, cyclin C, are components of the Mediator transcriptional regulatory complex, involved in both transcriptional activation and repression by phosphorylation of the carboxy-terminal domain of the largest subunit of RNA polymerase II. (genecards.org)
  • CDK has a catalytic subunit that is activated in the presence of a regulatory subunit provided by cyclin [ 7 ], which leads to the formation of a mediator complex together with MDE12 and MED13. (biomedcentral.com)
  • It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (wikipedia.org)
  • CDK2 kinase activity was inhibited 75% by PACAP, whereas kinase protein and its regulatory cyclin E subunit were unaffected. (jneurosci.org)
  • CDK2 and CDK1 are two closely related kinases that play overlapping roles during cell division, contributing to the phosphorylation and inactivation of the retinoblastoma (Rb) tumor suppressor gene product throughout late G 1 , S, and G 2 -M phases ( 5 - 7 ). (aacrjournals.org)
  • We now report that the endogenous peptide, pituitary adenylate cyclase activating polypeptide (PACAP), negatively regulates the cell cycle by inhibiting p57 Kip2 -dependent CDK2 activity in embryonic cortex. (jneurosci.org)
  • Indeed, immunoprecipitation of CDK2 complex revealed increased p57 Kip2 association with the kinase and concomitant reduction in free inhibitor after PACAP exposure, suggesting that p57 Kip2 interactions directly regulate CDK2 activity. (jneurosci.org)
  • Although early G 1 depends on cyclin D-dependent kinases, the late G 1 /S transition critically depends on cyclin E/CDK2 complexes, which phosphorylate retinoblastoma protein, allowing S-phase gene activation ( Sherr and Roberts, 1999 ). (jneurosci.org)
  • Consistent with a key role for CDK6 as a D-cyclin partner in thymocytes, knockout (KO) of CDK4 or CDK2 was shown to have no significant effect on T-cell development ( 11 , 12 ), but significantly decreased thymic cellularity was observed in a CDK6 KO animal ( 13 ). (aacrjournals.org)
  • To address this apparent paradox, we examined possible predictors of the sensitivity of 10 breast cancer cell lines to erlotinib in light of cyclin-dependent kinase 2 (CDK2), considered the farthest downstream kinase that controls cell cycling in the EGFR signaling pathway. (aacrjournals.org)
  • Reports that cell lines showing sensitivity to EGFR-TKIs showed G 1 arrest after treatment with EGFR-TKIs ( 11 - 13 ) led us to study the potential relationship between cyclin-dependent kinases (CDK), particularly CDK2 ( 12 , 13 ) and erlotinib sensitivity. (aacrjournals.org)
  • CDK2 regulates the G 1 -S phase transition and, within the EGFR signaling pathway, is the farthest downstream molecule with known kinase activity ( 13 - 15 ). (aacrjournals.org)
  • p16 Ink4 inhibited cdk4, but not cdk2, kinase activity, producing partial inhibition of VSMC growth in vitro. (ahajournals.org)
  • Progression through G 1 and entry into the S phase is regulated by the formation and activation of cyclin/cyclin-dependent kinase (CDK) complexes, predominantly cyclin D-cdk4/6 and cyclin E-cdk2. (ahajournals.org)
  • 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)
  • This protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. (creativebiomart.net)
  • Furthermore, cyclin C could be detected in K35 immunoprecipitates prepared from HeLa cells, indicating that the two proteins form a complex also in vivo. (unibas.ch)
  • Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a), CDKN2A and Rb were all found to be associated with tumorigenesis of a variety of cancers. (wikipedia.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)
  • CDK proteins remain constant throughout the cycle, whereas their activity is modulated by cyclin and CKI association. (jneurosci.org)
  • Here we demonstrate that the budding yeast cyclin-dependent kinase Cdc28 directly regulates the formation of the DNA double-strand breaks that initiate recombination by phosphorylating the Mer2/Rec107 protein and thereby modulating interactions of Mer2 with other proteins required for break formation. (pubmedcentralcanada.ca)
  • The cyclin-dependent kinase inhibitor flavopiridol has antitumor activity against hematopoietic malignancies, including CLL, in which induction of apoptosis was associated with reduced expression of antiapoptotic proteins. (aacrjournals.org)
  • Furthermore, E6-mediated regulation of the subcellular distribution of phospho-E6AP appears to be dependent, in part, upon the 14-3-3 family of proteins. (asm.org)
  • CDKN1B, also known as cyclin-dependent kinase inhibitor 1B, belongs to the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitor proteins. (creativebiomart.net)
  • This kinase regulates transcription by targeting the cyclin-dependent kinase 7 subunits of the general transcription initiation factor IIH, thus providing a link between the Mediator complex and the basal transcription machinery. (genecards.org)
  • Sirtuin 1 regulates SREBP-1c expression in a LXR-dependent manner in skeletal muscle. (wikipathways.org)
  • CDK6 is a multifunctional protein that negatively regulates both pRB and p27 KIP1 (p27) activity ( 7 ) and modulates differentiation of certain cells ( 8 ). (aacrjournals.org)
  • Thus, as cyclin D regulates one of the key initiating factors for cell cycle progression, the overexpression of this protein may render cells vulnerable to malignant transformation. (aacrjournals.org)
  • Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. (uniprot.org)
  • It is normally activated by cyclin C and is required for transcription elongation of the serum response genes (immediate early genes [IEGs]) FOS, EGR1, and cJUN. (sigmaaldrich.com)
  • [8] Most genes lack a TATA box and use an initiator element (Inr) or downstream core promoter instead. (wikipedia.org)
  • Cxs affect cell growth by affecting the expression of cell cycle regulatory genes, such as cyclin A, D1 and D2, and cyclin-dependent kinases ( 8 ). (spandidos-publications.com)
  • Transcriptome analysis of BCR-engaged B cells from Bach2 −/− mice revealed reduced expression of the antiapoptotic gene Bcl2l1 encoding Bcl-x L and elevated expression of cyclin-dependent kinase inhibitor (CKI) family genes, including Cdkn1a , Cdkn2a , and Cdkn2b . (jimmunol.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 G1/S transition. (wikipedia.org)
  • 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)
  • OSI Pharmaceuticals, Inc., and Genentech, Inc.) is an orally available quinazolinamine that competes with ATP for binding with the intracellular catalytic domain of EGFR tyrosine kinase (EGFR-TK) to inhibit the phosphorylation of EGFR-TK. (aacrjournals.org)
  • Indeed, this phosphorylation was observed 6 hours after p25 induction and was abolished in the presence of a Cdk5 inhibitor, roscovitine, which does not inhibit the usual Rb cyclin-D kinases Cdk4 and Cdk6. (biologists.org)
  • Conversely, c-myc overexpression can inhibit the Smad-dependent transcription of p15 and p21 ( 11 ). (aacrjournals.org)
  • Furthermore, MCF-7 cells treated with IV-2 showed increased Cdk1 kinase activity and a decrease in Cdk1 tyrosine phosphorylation, indicating that IV-2 did not directly inhibit Cdk1 or Cdc25 activities. (aspetjournals.org)
  • 2017 Feb 21;8(8):12558-12575. (nih.gov)
  • In this chapter, we discuss the activation mechanism of the CDK5 kinase within the general frame of reference of kinase activation mechanisms, and in comparison to other members of the CDK family. (springer.com)
  • We explain how CDK5, not unlike other kinases, has made its own capricious decisions to design an original activation mechanism and distinguish itself from CDK-family relatives. (springer.com)
  • Cyclin-dependent kinase 5 (cdk5) activation requires interaction with three domains of p35. (springer.com)
  • A model of the complex between cyclin-dependent kinase 5 and the activation domain of neuronal Cdk5 activator. (springer.com)
  • A Jekyll and Hyde kinase: roles for Cdk5 in brain development and disease. (springer.com)
  • The cerebral cortex of mice with a targeted disruption in the gene for cyclin-dependent kinase 5 ( cdk5 ) is abnormal in its structure. (jneurosci.org)
  • Cyclin-dependent kinase 5 (CDK5) is one of the major kinases involved in Tau phosphorylation, directly phosphorylating various residues and simultaneously regulating various substrates such as kinases and phosphatases that influence Tau phosphorylation in a synergistic and antagonistic way. (frontiersin.org)
  • The relationship among these theoretical and computational models shows that the regulation of Tau phosphorylation by PP2A and glycogen synthase kinase 3β (GSK3β) is essential under basal conditions and also describes the leading role of CDK5 under excitotoxic conditions, where silencing of CDK5 can generate changes in these enzymes to reverse a pathological condition that simulates AD. (frontiersin.org)
  • Furthermore, analyses of levels and subcellular localization of Cdk-related cyclins did not reveal any change following Cdk5 activation, arguing for a direct effect of Cdk5 activity on Rb protein. (biologists.org)
  • This latter result was clearly demonstrated by in vitro kinase assays showing that the p25-Cdk5 complex in our cell system phosphorylates Rb directly without the need for any intermediary kinase activity. (biologists.org)
  • Cdk5 is a pro-directed phosphorylation kinase that belongs to the cyclin-dependent-protein-kinase family. (biologists.org)
  • p35 is an activating co-factor of Cyclin-dependent kinase 5 (Cdk5), a protein whose dysfunction has been implicated in a wide-range of neurological disorders including cognitive impairment and disease. (frontiersin.org)
  • Retroviral cyclin controls cyclin-dependent kinase 8-mediated transcription elongation and reinitiation. (sigmaaldrich.com)
  • Previous work showed that the retroviral cyclin (RV-cyclin), encoded by WDSV, has separable cyclin box and transcription activation domains. (sigmaaldrich.com)
  • Quantitative reverse transcription-PCR (RT-PCR) and nuclear run-on assays provide evidence that RV-cyclin does not alter the initiation of IEG transcription but does enhance the overall rate of transcription elongation and maintains transcription reinitiation. (sigmaaldrich.com)
  • Because of analogy with yeast Cdk 8, it has been proposed that the human Cdk 8 Cyclin C may interact with RNA polymerase, thus influencing the transcription mechanism(s) that lead to cell division. (genetex.com)
  • 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)
  • The crucial role of DNA-dependent protein kinase and myelin transcription factor 1-like protein in the miR-141 tumor suppressor network. (harvard.edu)
  • The tail module (numbered subunits) interacts with DNA-bound transcription factors (TF and the dissociable kinase module. (g3journal.org)
  • Additional analysis demonstrated that flavopiridol treatment resulted in a dose-dependent inhibition of phosphorylation of the RNA polymerase II COOH-terminal domain, thus blocking transcription elongation. (aacrjournals.org)
  • We also provide evidence that the CKM acts as a corepressor for the Ets-family transcription factor LIN-1 , as cdk-8 promotes transcriptional repression by LIN-1 . (genetics.org)
  • GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity . (genecards.org)
  • Targeting tyrosine kinases in cancer: the second wave. (springer.com)
  • Global analysis of human nonreceptor tyrosine kinase specificity using high-density peptide microarrays. (uta.fi)
  • Expression of phosphorylated (p-)tyrosine, p-Akt, phosphorylated extracellular signal-regulated kinase (p-ERK) 1/ERK2 (p42/p44), and p27 after treatment of erlotinib was not associated with erlotinib sensitivity. (aacrjournals.org)
  • Cyclin D-CDK4 complexes are major integrators of various mitogenic and antimitogenic signals. (wikipedia.org)
  • Cyclin/CDK complexes were typically diluted to a final concentration of 50 μg/mL in a kinase reaction buffer containing 50 mmol/L Tris-HCl (pH 8.0), 10 mmol/L MgCl 2 , 1 mmol/L DTT, and 0.1 mmol/L sodium orthovanadate. (aacrjournals.org)
  • The CKIs p27 Kip1 and p21 Cip1 inactivate the cyclin-CDK complexes in the G 1 phase leading to cell cycle arrest, and thus function in growth regulation and wound repair. (ahajournals.org)
  • 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)
  • Drosophila RSK influences the pace of the circadian clock by negative regulation of protein kinase Shaggy activity. (sdbonline.org)
  • The CK2 Kinase Stabilizes CLOCK and Represses Its Activity in the Drosophila Circadian Oscillator. (sdbonline.org)
  • Protein kinase CK2 links polyamine metabolism to MAPK signalling in Drosophila. (sdbonline.org)
  • Sxl-dependent, tra/tra2 -independent alternative splicing of the Drosophila melanogaster X-Linked gene found in neurons. (sdbonline.org)
  • Negative regulation of MAP kinase signaling in Drosophila by Ptp61F/PTP1B. (sdbonline.org)
  • Drosophila larval salivary glands of varying Drosophila phosphatidylinositol 5 phosphate 4-kinase (dPIP 4 K) activity, stained with fluorescent dyes to outline individual cells and their membranes. (portlandpress.com)
  • Rogulja D, Young M. Control of sleep by cyclin A and its regulator. (labome.org)
  • Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. (curehunter.com)
  • Cyclin-dependent kinase 6 (CDK6), a cyclin D-responsive regulator of the retinoblastoma protein (pRB) pathway, seems to be of central importance in T-cell development. (aacrjournals.org)
  • 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 p16INK4a. (wikipedia.org)
  • The complex is structurally divided into four modules known as the head, middle, tail and kinase modules, and in Arabidopsis thaliana , comprises 28-34 subunits. (g3journal.org)
  • The individual subunits of the complex have been assigned to four modules, known as the head, middle, tail, and kinase modules, based on their positions within the complex ( Figure 1 ). (g3journal.org)
  • Menin plays a role in regulating cellular proliferation because Men1 knockout mice show increased proliferation in neuroendocrine tissues ( 7 ), down-modulation of menin in epithelial cells stimulates proliferation ( 8 ), and menin knockout fibroblasts proliferate more rapidly than wild-type cells as assayed by tritiated thymidine incorporation ( 9 ). (pnas.org)
  • Extracellular-Regulated Protein Kinase 5-Mediated Control of p21 Expression Promotes Macrophage Proliferation Associated with Tumor Growth and Metastasis. (harvard.edu)
  • Using the OP9-DL1 system to deliver temporally controlled Notch receptor-dependent signaling, we show that CDK6 is required for Notch-dependent survival, proliferation, and differentiation. (aacrjournals.org)
  • it was first described as a potent inhibitor of cell proliferation and DNA replication, both in physiological conditions and after DNA damage [ 7 , 8 ]. (intechopen.com)
  • Using a dominant negative approach, in vitro cell proliferation assays, western blots, and flow cytometry showed that MAPK signaling via BRAFV600E promotes melanoma cell proliferation at G1 through AP-1-mediated negative regulation of the INK4 family member, cyclin-dependent kinase inhibitor 2C (CDKN2C), and the CIP/KIP family member, cyclin-dependent kinase inhibitor 1A (CDKN1A). (harvard.edu)
  • Melzer, J., Kraft, K. F., Urbach, R., Raabe, T. (2013) The p21-activated kinase Mbt is a component of the apical protein complex in central brain neuroblasts and controls cell proliferation. (sdbonline.org)
  • MG132 dose-dependently inhibited vascular smooth muscle cell proliferation with 50% inhibition at 10 μmol/L. TNFα-induced degradation of IκBα and β was blocked, and activation of nuclear factor kappa B was suppressed in a concentration-dependent manner in bandshift assays. (ahajournals.org)
  • We show that UP blocks the proliferation of purified peripheral human T and B lymphocytes with an IC50 of 3 to 8 ng/ml and following stimulation by all mitogens used, with no effect on cell death. (jimmunol.org)
  • Accelerated turnover of taste bud cells in mice deficient for the cyclin-dependent kinase inhibitor p27Kip1. (biomedsearch.com)
  • The cyclin-dependent kinase inhibitor p27Kip1 has been shown to influence cell number in several developing tissues, by coordinating cell cycle exit during cell differentiation. (biomedsearch.com)
  • Elevated activity of cyclin-dependent kinase 6 in human squamous cell carcinoma lines -- Timmermann et al. (aacrjournals.org)
  • Elevated activity of cyclin-dependent kinase 6 (cdk6), a pRB kinase, was detected in all five squamous cell carcinoma lines. (aacrjournals.org)
  • TFIIH has three functions: It binds specifically to the template strand to ensure that the correct strand of DNA is transcribed and melts or unwinds the DNA ( ATP -dependent) to separate the two strands using its helicase activity. (wikipedia.org)
  • Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. (wikipedia.org)
  • Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (wikipedia.org)
  • Effects of phosphorylation of threonine 160 on cyclin-dependent kinase 2 structure and activity. (springer.com)
  • It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18. (curehunter.com)
  • Moreover, decreased kinase activity was accompanied by a twofold increase in levels of p57 Kip2 protein, but not p21 Cip1 or p27 Kip1 , suggesting that p57 Kip2 mediates PACAP anti-mitogenic effects. (jneurosci.org)
  • Shortly after its purification, P-TEFb was found to have protein kinase activity ( 50 ). (asm.org)
  • Recent studies identified an autism-linked mutation within E6AP at T485, which was identified as a protein kinase A phosphoacceptor site and which could directly regulate E6AP ubiquitin ligase activity. (asm.org)
  • Cyclin D exerts its action via CDK4, and in Mv1Lu mink lung epithelial cells, cyclin D overexpression was found to induce Smad3 linker phosphorylation via CDK4, which led to inhibition of wild-type (WT) Smad3 activity ( 18 , 19 ). (aacrjournals.org)
  • 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)
  • This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). (wikipedia.org)
  • Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. (curehunter.com)
  • Associated with cyclin-D, CDK4 phosphorylates and inactivates retinoblastoma (Rb) protein family members and mediates progression through the G1- to the S-phase of the cell cycle. (springer.com)
  • Characterization of the new immunosuppressive drug undecylprodigiosin in human lymphocytes: retinoblastoma protein, cyclin-dependent kinase-2, and cyclin-dependent kinase-4 as molecular targets. (jimmunol.org)
  • The induction of cyclin D2 and the decrease in p27 were not inhibited by UP, whereas the induction of cyclin E, cyclin A, cyclin-dependent kinase-2, and cyclin-dependent kinase-4 was strongly inhibited, potentially explaining the inhibition of retinoblastoma protein phosphorylation. (jimmunol.org)
  • 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)
  • 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)
  • Here, we summarize our current understanding of the RNAPII-directed protein kinases in cardiac hypertrophy. (ahajournals.org)
  • In the last 15 years, a wealth of structural investigations on protein kinases has been reported. (springer.com)
  • These studies have revealed that the active states of protein kinases are usually structurally alike, a requirement imposed by the necessity to maintain the basic geometry of a highly conserved machinery required for good catalytic output. (springer.com)
  • Signalling specificity of Ser/Thr protein kinases through docking-site-mediated interactions. (springer.com)
  • We are investigating the signalling pathways that regulate cell division, with a view to identifying the component enzymes and investigating their roles in cell division, and have previously validated a number of cell division protein kinases as drug targets (4-6). (gla.ac.uk)
  • More recently, we performed an RNA interference screen of the trypanosome kinome, and linked a number of protein kinases to cell cycle roles in bloodstream form T. brucei for the first time (7). (gla.ac.uk)
  • Cyclin-dependent kinase 6 (CDK6) promotes cell cycle progression and is overexpressed in human lymphoid malignancies. (aacrjournals.org)
  • These results show a critical requirement for CDK6 in Notch/Akt-dependent T-cell development and tumorigenesis and strongly support CDK6 as a specific therapeutic target in human lymphoid malignancies. (aacrjournals.org)
  • In contrast, cyclin D2 expression is high in the DN1-DN3 stages before pre-TCR assembly and barely detectable after pre-TCR assembly ( 10 ), suggesting that CDK6 may use different cyclin partners in the thymocyte developmental stages. (aacrjournals.org)
  • The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases. (springer.com)
  • Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition. (springer.com)
  • TFIIH is a large protein complex that contains among others the CDK7 / cyclin H kinase complex and a DNA helicase. (wikipedia.org)
  • Cell division protein kinase 7 is an enzyme that in humans is encoded by the CDK7 gene . (wikidoc.org)
  • Trypanosome cell division, especially its final stage (cytokinesis) is very divergent from mammalian cell division (1-3) , suggesting that a better understanding of the protein kinase (PK) signalling pathways regulating it would reveal novel drug targets. (gla.ac.uk)
  • Activation of each phase is dependent on the proper progression and completion of the previous one. (wikibooks.org)
  • Depending on tumour progression, GJIC has different functions ( 8 ). (spandidos-publications.com)
  • The cyclin D-CDK4/6 complex is critical to cell cycle progression, as it induces phosphorylation inhibition of the Rb protein. (aacrjournals.org)
  • A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. (harvard.edu)
  • Kinase requirements in human cells: II. (aacrjournals.org)
  • Metazoan cyclin C was originally isolated by virtue of its ability to rescue Saccharomyces cerevisiae cells deficient in G1 cyclin function. (unibas.ch)
  • It works by inhibiting cyclin-dependent kinases, arresting cell division and causing apoptosis in non-small lung cancer cells. (drugbank.ca)
  • Recombinant cyclin/CDK holoenzymes were purified from Sf9 cells engineered to produce baculoviruses that express a specific cyclin or CDK. (aacrjournals.org)
  • An indolocarbazole that is a potent protein kinase C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (drugbank.ca)
  • Morphological plasticity is a key requirement for biofilm formation [8] , as this process involves initial attachment to a surface by yeast cells which germinate to form a matrix-encased hyphal network [9] . (prolekare.cz)
  • It has been shown that Notch-promoted survival and trophic effects in pre-T cells are mediated by the phosphatidylinositol 3-kinase (PI3K)-Akt pathway ( 6 ). (aacrjournals.org)
  • cdk-8 inhibits ectopic vulva formation by acting downstream of mpk-1 /ERK , cell autonomously in vulval cells, and in a kinase-dependent manner. (genetics.org)
  • Cx subtypes increase the attachment of tumour cells to the stroma ( 8 ) and the endothelial barrier ( 16 ), thereby promoting invasion and metastatic spread. (spandidos-publications.com)
  • While these animals were found to have deficiencies in hippocampal-dependent spatial learning and alterations in in vitro synaptic plasticity, interpretation of these phenotypes is complicated as a result of the changes in the gross anatomy. (frontiersin.org)
  • Subsequent work examining a panel of MCF-10A premalignant and transformed malignant mammary cell lines showed that Smad2/3 signaling conferred both tumor-suppressant and oncogenic effects, dependent on the primary or metastatic environment ( 16 ). (aacrjournals.org)
  • Flavopiridol has been tested at various dosing levels and schedules in both hematologic ( 7, 8 ) and solid tumor malignancies ( 3 , 9 , 10 ). (aacrjournals.org)
  • By Western blot, this antibody detects a band of 54 kDa, which corresponds to the predicted molecular weight of Cdk 8. (genetex.com)
  • Molecular motions of human cyclin-dependent kinase 2. (springer.com)
  • "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C" . Proceedings of the National Academy of Sciences of the United States of America . (wikipedia.org)
  • Region between residue 420 and 470 of human cyclindependent kinase 8 using the numbering given in entry NP_001251.1 (GeneID 1024). (antikoerper-online.de)
  • Cyclin D overexpression is pervasive in human breast cancers, including heritable breast cancers with BRCA2 mutations ( 22 - 24 ). (aacrjournals.org)
  • All the patients completed an 8-week trial of twice-daily application of human growth factor and hyaluronic acid serum on the entire face. (jove.com)
  • This action blocks downstream signal transduction and inhibits the tumorigenic effects associated with ligand-dependent and ligand-independent EGFR activation ( 1 , 2 ). (aacrjournals.org)
  • At the EGR1 gene locus, RV-cyclin increases and maintains RNA polymerase II (Pol II) occupancy after serum stimulation, in conjunction with increased and extended EGR1 gene expression. (sigmaaldrich.com)
  • The K35-cyclin C complex is structurally related to SRB10-SRB11, a CDK-cyclin pair recently shown to be part of the RNA polymerase II holoenzyme of S. cerevisiae. (unibas.ch)
  • Cardiac differentiation in Xenopus requires the cyclin-dependent kinase inhibitor, p27Xic1. (biomedsearch.com)
  • Here we show that constitutive expression of RV-cyclin in the HCT116 colon cancer cell line significantly increases the level of IEG expression in response to serum stimulation. (sigmaaldrich.com)