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.

Comparative molecular genetic profiles of anaplastic astrocytomas/glioblastomas multiforme and their subsequent recurrences. (1/1100)

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

Coupling of the cell cycle and myogenesis through the cyclin D1-dependent interaction of MyoD with cdk4. (2/1100)

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

Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. (3/1100)

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

Induced expression of p16(INK4a) inhibits both CDK4- and CDK2-associated kinase activity by reassortment of cyclin-CDK-inhibitor complexes. (4/1100)

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

Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (5/1100)

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

Progesterone inhibits estrogen-induced cyclin D1 and cdk4 nuclear translocation, cyclin E- and cyclin A-cdk2 kinase activation, and cell proliferation in uterine epithelial cells in mice. (6/1100)

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

Re-expression of endogenous p16ink4a in oral squamous cell carcinoma lines by 5-aza-2'-deoxycytidine treatment induces a senescence-like state. (7/1100)

We have previously reported that a set of oral squamous cell carcinoma lines express specifically elevated cdk6 activity. One of the cell lines, SCC4, contains a cdk6 amplification and expresses functional p16ink4a, the other cell lines express undetectable levels of p16ink4a, despite a lack of coding-region mutations. Two of the cell lines, SCC15 and SCC40 have a hypermethylated p16ink4A promoter and a third cell line, SCC9, has a mutation in the p16ink4a promoter. Using the demethylation agent 5-aza-2'-deoxycytidine, we showed that the p16ink4a protein was re-expressed after a 5-day treatment with this chemical. One cell line, SCC15 expressed high levels of p16ink4a. In this line, cdk6 activity was decreased after 5-aza-2'deoxycytidine treatment, and the hypophosphorylated, growth suppressive form of the retinoblastoma tumor suppressor protein pRB was detected. Expression of p16ink4a persisted, even after the drug was removed and the cells expressed senescence-associated beta-galactosidase activity. Ectopic expression of p16ink4a with a recombinant retrovirus in this cell line also induced a similar senescence-like phenotype. Hence, it was possible to restore a functional pRB pathway in an oral squamous cell carcinoma line by inducing re-expression of endogenous p16ink4a in response to treatment with a demethylating agent.  (+info)

Defining the substrate specificity of cdk4 kinase-cyclin D1 complex. (8/1100)

cdk4 kinase-cyclin D1 complex (cdk4/D1) does not phosphorylate all of the sites within retinoblastoma protein (Rb) equally. Comparison of five phosphorylation sites within the 15 kDa C domain of Rb indicates that Ser795 is the preferred site of phosphorylation by cdk4/D1. A series of experiments has been performed to determine the properties of this site that direct preferential phosphorylation. For cdk4/D1, the preferred amino acid at the third position C-terminal to the phosphorylated serine/threonine is arginine. Substitution of other amino acids, including a conservative change to lysine, has dramatic effects on the rates of phosphorylation. This information has been used to mutate less favorable sites in Rb, converting them to sites that are now preferentially phosphorylated by cdk4/D1. A conserved site at Ser842 in the related pocket protein p107 is also preferentially phosphorylated by cdk4/D1. Although Rb and p107 differ significantly in sequence, the Rb Ser795 site can replace the p107 Ser842 site without affecting the rate of phosphorylation. These results suggest that although a determinant of specificity resides in the sequences surrounding the phosphorylated site, the structural context of the site is also a critical parameter of specificity.  (+info)

AZD5438 is a potent inhibitor of CDK1/2/9 with IC50 of 16 nM/6 nM/20 nM. It is less potent to CDK5/6 and also inhibits GSK3β. Phase 1.Quality confirmed by NMR & HPLC. See customer reviews, validations & product citations.
Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) and adventitial fibroblasts play an important role in the pathobiology of vascular occlusive disease (eg, atherosclerosis, in-stent restenosis, transplant vasculopathy, and vessel bypass graft failure).1,2 Thus, understanding the molecular mechanisms that control hyperplastic growth and the locomotion of vascular cells should aid in the development of novel therapeutic strategies to reduce neointimal thickening.. Cell cycle progression is controlled by several cyclin-dependent kinases (CDKs) that associate with regulatory cyclins.3 Mitogenic stimuli activate CDK/cyclin holoenzymes, thus causing hyperphosphorylation of the retinoblastoma protein (pRb) and related pocket proteins from mid G1 to mitosis. CDK-dependent pRb hyperphosphorylation releases E2F transcription factors, thus contributing to the expression of several growth and cell cycle-regulatory genes with functional E2F-binding sites in their ...
The cyclin-dependent kinase (CDK) inhibitor p27Kip1 has been shown to regulate cellular proliferation via inhibition of CDK activities. routine and g27Kip1 (hereafter g27) can regulate CDK actions.1-3 The p27 protein was originally known as an inhibitor of CDK activities for things containing CDK2 and shown to inhibit cyclin E and cyclin A activities which regulate G1 and S phase traverse.4-6 In addition to CDK inhibition, g27 provides other multifarious connections with cyclin N/cdk4 processes putatively.7 Since cellular amounts of g27 are elevated in response to high cell thickness, serum deprival, and TGF, it was hypothesized g27 brought cells into quiescence and held them in G0 through the inhibition of CDK actions.8 Numerous reviews have got characterized the control of p27 including the control of its transcription,9,10 translation,11,12 post-translational adjustments.7,13,14 cellular localization15-19 and balance.20-23 The regulations of its stability has a main role in adjusting mobile ...
Phosphorylation of Sic1, a Cyclin-dependent Kinase (Cdk) Inhibitor, by Cdk Including Pho85 Kinase Is Required for Its Prompt Degradation: In the yeast Saccharom
Recombinant Cyclin-Dependent Kinase 10 (CDK10) Protein (His tag). Species: Cow (Bovine). Source: Yeast. Order product ABIN1616360.
Recombinant Cyclin-Dependent Kinase 10 (CDK10) Protein (His tag). Species: Human. Source: Insect Cells. Order product ABIN3091398.
View mouse Cdk11b Chr4:155624854-155649938 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
Lerociclib dihydrochloride (G1T38 dihydrochloride) is a potent and selective inhibitor of CDK4/CDK6, with IC50s of 1 nM and 2 nM for CDK4/CyclinD1 and CDK6/CyclinD3, respectively.
pep:known chromosome:VEGA66:5:146231288:146302874:1 gene:OTTMUSG00000025856 transcript:OTTMUST00000063710 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Cdk8 description:cyclin-dependent kinase 8 ...
Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
Gentaur molecular products has all kinds of products like :search , GenWay \ Cyclin-Dependent Kinase 4 - EC 2.7.11.22; Cyclin-dependent kinase 4; PSK-J3 \ 10-288-22309F for more molecular products just contact us
CDKs (Cyclin-dependent kinases) are serine-threonine kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. CDKs are relatively small proteins, with molecular weights ranging from 34 to 40 kDa, and contain little more than the kinase domain. In fact, yeast cells can proliferate normally when their CDK gene has been replaced with the homologous human gene. By definition, a CDK binds a regulatory protein called a cyclin. Without cyclin, CDK has little kinase activity; only the cyclin-CDK complex is an active kinase.. There are around 20 Cyclin-dependent kinases (CDK1-20) known till date. CDK1, 4 and 5 are involved in cell cycle, and CDK 7, 8, 9 and 11 are associated with transcription.. CDK levels remain relatively constant throughout the cell cycle and most regulation is post-translational. Most knowledge of CDK structure and function is based on CDKs of S. pombe (Cdc2), S. ...
Cyclin-dependent kinases (CDKs) are protein kinases characterized by needing a separate subunit - a cyclin - that provides domains essential for enzymatic activity. CDKs play important roles in the control of cell division and modulate transcription in response to several extra- and intracellular cues. The evolutionary expansion of the CDK family in mammals led to the division of CDKs into three cell-cycle-related subfamilies (Cdk1, Cdk4 and Cdk5) and five transcriptional subfamilies (Cdk7, Cdk8, Cdk9, Cdk11 and Cdk20). Unlike the prototypical Cdc28 kinase of budding yeast, most of these CDKs bind one or a few cyclins, consistent with functional specialization during evolution. This review summarizes how, although CDKs are traditionally separated into cell-cycle or transcriptional CDKs, these activities are frequently combined in many family members. Not surprisingly, deregulation of this family of proteins is a hallmark of several diseases, including cancer, and drug-targeted inhibition of specific
Coxon CR, Anscombe E, Harnor SJ, Martin MP, Carbain B, Golding BT, Hardcastle IR, Harlow LK, Korolchuk S, Matheson CJ, Newell DR, Noble ME, Sivaprakasam M, Tudhope SJ, Turner DM, Wang LZ, Wedge SR, Wong C, Griffin RJ, Endicott JA, Cano C. Cyclin-Dependent Kinase (CDK) Inhibitors: Structure-Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines. J Med Chem. 2017 03 09; 60(5):1746-1767 ...
https://astx.com/wp-content/uploads/2019/11/logo_white.png 0 0 webadmin https://astx.com/wp-content/uploads/2019/11/logo_white.png webadmin2010-11-29 12:06:482016-11-29 12:06:57Cho et al. 4-(Pyrazol-4-yl)-pyrimidines as Selective Inhibitors of Cyclin-Dependent Kinase 4/6. Journal of Medicinal Chemistry 53, no. 22 2010: 7938-7957. DOI: 10.1021/jm100571n. ...
Unicellular organisms such as yeasts require a single cyclin-dependent kinase, Cdk1, to drive cell division. In contrast, mammalian cells are thought to require the sequential activation of at least four different cyclin-dependent kinases, Cdk2, Cdk3, Cdk4 and Cdk6, to drive cells through interphase …
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
P 276 is a flavone that selectively inhibits the cyclin-dependent kinases Cdk4-D1, Cdk9-T and Cdk1-B, thus inhibiting the pathways necessary for cancer cell
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Alsterpaullone, cyclin-dependent kinase (CDK) and GSK-3beta inhibitor (CAS 237430-03-4), with |96% purity. Join researchers using our high quality biochemicals.
Complete information for CDK10 gene (Protein Coding), Cyclin Dependent Kinase 10, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for CDK4 gene (Protein Coding), Cyclin Dependent Kinase 4, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
NU2058 (O6-(Cyclohexylmethyl)guanine) is a potent, competitive and guanine-based CDK inhibitor with IC50s of 17 μM and 26 μM for CDK2 and CDK1. NU2058 has anti-cancer activity. - Mechanism of Action & Protocol.
1GIH: Crystallographic approach to identification of cyclin-dependent kinase 4 (CDK4)-specific inhibitors by using CDK4 mimic CDK2 protein.
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The randomised controlled trial (RCT) is the gold standard for evaluating the effects of health care interventions.1 Therefore, South African health policy and clinical guidelines should be based on well-conducted RCTs that ideally are conducted within the country to ensure local applicability. Conducting RCTs in South Africa faces numerous obstacles. Specialist training in the universities traditionally focuses on clinical experience and skills accrual, and lacks a research focus. Downscaled tertiary service units struggle to remain academically active,2 reducing the opportunities for local clinicians to acquire the epidemiological and statistical skills for conducting RCTs. Health professionals interested in clinical research may have to migrate to develop these skills. Opportunities to then practise those skills may only exist overseas, contributing to the professional brain drain.3 When research funding is not available from local sources, researchers become dependent on funds from donor ...
Progress through the G1phase of the mammalian cell cycle is regulated by the ordered synthesis, assembly, and activation of distinct cyclin-CDK holoenzymes (45, 46). Cyclins D1, D2, and D3 are up-regulated as cells exit from quiescence and associate with their major kinase partners CDK4 and CDK6 (3, 29, 32, 53). These two kinase molecules are highly homologous and associate exclusively with the D-type cyclins (3). Numerous studies have implicated cyclin D-CDK4-CDK6 complexes as key regulators of the cell cycle up to a hypothetical point during late G1 (24, 25), the restriction point, when hyperphosphorylation and inactivation of the retinoblastoma tumor suppressor gene product, pRB, occur (37, 44).. In contrast to mitotic cyclin-CDK complexes, the D-type cyclins do not automatically assemble into complexes with either CDK4 or CDK6. For example, when overexpressed in NIH 3T3 cells in the absence of serum, D-type cyclins and CDK4 do not interact efficiently (30). Hence, assembly of D-type cyclins ...
TY - JOUR. T1 - Molecular cloning of a cyclin-like protein associated with cyclin-dependent kinase 3 (cdk 3) in vivo. AU - Matsuoka, Masaaki. AU - Matsuura, Yoshiharu. AU - Semba, Kentaro. AU - Nishimoto, Ikuo. PY - 2000/7/5. Y1 - 2000/7/5. N2 - cdk3 has been considered to be rate-limiting for cell cycle progression of mammalian cells while its precise function remains to be elucidated, To assess cdk3 function, a cDNA coding for a cyclin-like protein (designated as ik3-1 from an interactor-1 with cdk3) was isolated with the yeast two-hybrid system using a cyclin-dependent kinase 3 (cdk3) cDNA as bait. p70(ik3-1) (a 70-kDa protein designated as p70(ik3-1)) seems to belong to the cyclin family as its C-terminal domain composed of 124 amino acids resembles the highly conserved cyclin box. Coimmunoprecipitation indicated that p70(ik3-1) binds to p35(cdk3) in vivo. The ik3-1 gene may belong to a multigene family and is highly conserved during evolution. mRNA expression of ik3-1 was low in the early ...
TY - JOUR. T1 - Systematic determination of human cyclin dependent kinase (CDK)-9 interactome identifies novel functions in RNA splicing mediated by the DEAD Box (DDX)-5/17 RNA helicases. AU - Yang, Jun. AU - Zhao, Yingxin. AU - Kalita, Mridul. AU - Li, Xueling. AU - Jamaluddin, Mohammad. AU - Tian, Bing. AU - Edeh, Chukwudi B.. AU - Wiktorowicz, John E.. AU - Kudlicki, Andrzej. AU - Brasier, Allan R.. PY - 2015/10/1. Y1 - 2015/10/1. N2 - Inducible transcriptional elongation is a rapid, stereotypic mechanism for activating immediate early immune defense genes by the epithelium in response to viral pathogens. Here, the recruitment of a multifunctional complex containing the cyclin dependent kinase 9 (CDK9) triggers the process of transcriptional elongation activating resting RNA polymerase engaged with innate immune response (IIR) genes. To identify additional functional activity of the CDK9 complex, we conducted immunoprecipitation (IP) enrichment-stable isotope labeling LC-MS/MS of the CDK9 ...
Cyclin-dependent kinase 4 inhibitor D (CDKN2D) is a specific inhibitor of cyclin-dependent kinases CDK4 and CDK6. CDK4 is a subunit of the protein kinase complex that is important for cell cycle G1 ph...
Dive into the research topics of An analysis of available biomarker data for targeting cyclin-dependent kinases 4 and 6 (CDK4/6) in breast cancer. Together they form a unique fingerprint. ...
Disruption of the cyclin-dependent kinase-inhibitory domain of p27 enhances growth of mice. Growth is attributed to an increase in cell number, due to increased cell proliferation, most obviously in tissues that ordinarily express p27 at the highest levels. Disruption of p27 function leads to nodula …
Dinaciclib, also known as SCH727965, is a potent CDK inhibitor with potential antineoplastic activity. Dinaciclib selectively inhibits cyclin dependent kinases CDK1, CDK2, CDK5, and CDK9 activity in vitro with IC(50) values of 1, 1, 3, and 4 nmol/L, respectively. Compared with flavopiridol, Dinaciclib exhibits superior activity with an improved therapeutic index. Dinaciclib induced regression of established solid tumors in a range of mouse models following intermittent scheduling of doses below the maximally tolerated level..
1KE9: Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis.
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Cdk5r1 - Cdk5r1 (Myc-DDK-tagged ORF) - Rat cyclin-dependent kinase 5, regulatory subunit 1 (p35) (Cdk5r1), (10 ug) available for purchase from OriGene - Your Gene Company.
Cdk14 - Cdk14 (Myc-DDK-tagged) - Mouse cyclin-dependent kinase 14 (Cdk14) available for purchase from OriGene - Your Gene Company.
Looking for online definition of cyclin-dependent kinase 15 in the Medical Dictionary? cyclin-dependent kinase 15 explanation free. What is cyclin-dependent kinase 15? Meaning of cyclin-dependent kinase 15 medical term. What does cyclin-dependent kinase 15 mean?
TY - JOUR. T1 - SU9516, a cyclin-dependent kinase 2 inhibitor, promotes accumulation of high molecular weight E2F complexes in human colon carcinoma cells. AU - Yu, Bo. AU - Lane, Maureen E.. AU - Wadler, Scott. PY - 2002/10/1. Y1 - 2002/10/1. N2 - The E2F family plays a critical role in the expression of genes required for entry into and progression through S phase. E2F-mediated transcription is repressed by the tumor suppressor retinoblastoma protein (pRb), which results in sequestration of E2F in a multiprotein complex that includes pRb. Derepression of E2F results from a series of complex phosphorylation events mediated by cyclin D/cdk4 and cyclin E/cdk2. We have employed a novel 3-substituted indolinone compound, 3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516), which selectively inhibits cdk2 activity (Lane et al., Cancer Res 2001;61:6170-7) to investigate these events. Electrophoretic mobility gel shift assays were performed on SU9516-treated and ...
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If you have a question about this talk, please contact Caroline Newnham.. Host: Viji Draviam. Tissue homeostasis in metazoans is regulated by transitions of cells between quiescence and proliferation. The hallmark of proliferating populations is progression through the cell cycle, which is driven by Cyclin-dependent kinase (CDK) activity. I will discuss our recent development of a live-cell sensor for CDK2 activity and the finding that proliferating cells bifurcate into two populations as they exit mitosis. Some cells immediately commit to the next cell cycle by building up CDK2 activity from an intermediate level, while other cells lack CDK2 activity and enter a transient state of quiescence. This bifurcation is directly controlled by the CDK inhibitor p21 and is regulated by mitogens during a restriction window at the end of the previous cell cycle. We are currently exploring the role of cell stress in controlling this bifurcation in an attempt to uncover the root cause of this striking ...
Abstract. Dysregulation of cyclin-dependent kinase (CDK)4 or CDK6 activity by gain of function or loss of inhibition is one of the most frequent aberrations in
Cyclin-dependent kinases (CDKs) are core components of the cell cycle machinery that govern the transition between phases during cell cycle progression. Genes involved in cell cycle are frequently mutated in human cancer and deregulated CDK activity repr
The researchers examined a protein called cyclin-dependent kinase 2 (CDK2), which works as a quality control inspector. As normal cells divide, they pause in the replication process when they find inaccurate genetic code embedded in their DNA. The health and well-being of offspring cells depends on accurate genetic code transfer from one generation of cells to the next. The Mayo researchers showed that when errors in genes are irreparable, CDK2 modifies another cellular protein -- FOXO1 -- to send a signal that results in the death of the cell. This protein-to-protein relationship invites targeted drug intervention to control unregulated growth of cancer cells ...
HMN-214 inhibits polo-like and cyclin-dependent kinase activity, has potent antimicrotubular effects and results in profound apoptosis and antitumor activity in a broad spectrum of human xenografts.
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A stable environment minimizes evapora- tive heat loss. 10. Cyclin-dependent kinases participate recomendaad death of neurons evoked by DNA- damaging agents. Daleiden, A.
The i-CDK9-induced increase in CDK9s binding to the MYC locus is mostly BRD4-dependent.DOI:http://dx.doi.org/10.7554/eLife.06535.017
protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. Sci. U.S. ... cyclin binding. • cyclin-dependent protein serine/threonine kinase activity. • macromolecular complex binding. ... 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 (Apr 1994). "Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase ... Receptor tyrosine kinases (RTKs) play a key role in the communication of cells with their microenvironment. These molecules are ... Perez JL, Jing SQ, Wong TW (Apr 1996). "Identification of two isoforms of the Cak receptor kinase that are coexpressed in ... Weiner TM, Liu ET, Craven RJ, Cance WG (Jan 1994). "Expression of growth factor receptors, the focal adhesion kinase, and other ...
... has been shown to interact with Cyclin-dependent kinase 4, MAP4K1 and ZAP-70. GRCh38: Ensembl release 89: ... "The SH3 domain-containing adaptor HIP-55 mediates c-Jun N-terminal kinase activation in T cell receptor signaling". J. Biol. ... "The SH3 domain-containing adaptor HIP-55 mediates c-Jun N-terminal kinase activation in T cell receptor signaling". J. Biol. ... that interacts with hematopoietic progenitor kinase 1". J. Biol. Chem. 274 (48): 33945-50. doi:10.1074/jbc.274.48.33945. PMID ...
Cyclin-dependent kinase 4 inhibitor C is an enzyme that in humans is encoded by the CDKN2C gene. The protein encoded by this ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". Ewing RM, Chu P, Elisma F, Li H, Taylor P, ... Fåhraeus R, Laín S, Ball KL, Lane DP (1998). "Characterization of the cyclin-dependent kinase inhibitory domain of the INK4 ... CDKN2C has been shown to interact with Cyclin-dependent kinase 4 and Cyclin-dependent kinase 6. GRCh38: Ensembl release 89: ...
... has been shown to interact with: BEGAIN, BRCA1, BRF1, Cyclin A2, Cyclin-dependent kinase 2, E2F1 ... "Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4". Molecular and ... Joaquin M, Watson RJ (Nov 2003). "The cell cycle-regulated B-Myb transcription factor overcomes cyclin-dependent kinase ... "Regulation of the retinoblastoma protein-related protein p107 by G1 cyclin-associated kinases". Proceedings of the National ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... "Entrez Gene: CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)". Tu Q, Hao J, Zhou X, Yan L, Dai H, Sun B, et al ... Cyclin-dependent kinase 4 inhibitor B also known as multiple tumor suppressor 2 (MTS-2) or p15INK4b is a protein that is ... This gene encodes a cyclin-dependent kinase inhibitor, also known as p15Ink4b protein, which forms a complex with CDK4 or CDK6 ...
"The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner". ... "The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner". ... SERTAD1 has been shown to interact with: CREB-binding protein, Cyclin-dependent kinase 4, and P16. GRCh38: Ensembl release 89: ... 7 Suppl 2: 155-6. doi:10.1007/978-94-009-5612-4_52. ISBN 978-94-010-8975-3. PMID 6434876. Sugimoto M, Nakamura T, Ohtani N, ...
p16 inhibits cyclin dependent kinases 4 and 6 (CDK4 and CDK6) and thereby activates the retinoblastoma (Rb) family of proteins ... "CDKN2A cyclin dependent kinase inhibitor 2A [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-10-11. ... CDKN2A, also known as cyclin-dependent kinase inhibitor 2A, is a gene which in humans is located at chromosome 9, band p21.3. ... "CDKN2A - Cyclin-dependent kinase inhibitor 2A - Homo sapiens (Human) - CDKN2A gene & protein". www.uniprot.org. Retrieved 2016- ...
Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene. The protein encoded by this ... "Entrez Gene: CDKN2D cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4)". Hirai H, Roussel MF, Kato JY, et al. (1995). " ... 1998). "Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d". ... 2002). "Evidence of a role for the INK4 family of cyclin-dependent kinase inhibitors in ovarian granulosa cell tumors". Genes ...
"Calmodulin is essential for cyclin-dependent kinase 4 (Cdk4) activity and nuclear accumulation of cyclin D1-Cdk4 during G1". ...
Trilaciclib is an inhibitor of cyclin-dependent kinase 4/6 approved for the prevention of myelosuppression caused by ... For this reason the effect on the cell is dose dependent; the fraction of cells that die is directly proportional to the dose ... Unlike alkylating agents, anti-metabolites are cell cycle dependent. This means that they only work during a specific part of ... By contrast, other inhibitions of growth-signals like those associated with receptor tyrosine kinases are referred to as ...
The p16 protein is a cyclin dependent kinase inhibitor (CDK) inhibitor and it activates Rb tumor suppressor. p16 binds to CDK 4 ... p16Ink4a also activates pRB, but through inactivation of cyclin-dependent kinase 4 (Cdk 4) and cyclin-dependent kinase 6 (Cdk 6 ... p53 activates p21 which deactivates cyclin-dependent kinase 2(Cdk 2). Without Cdk 2, retinoblastoma protein (pRB) remains in ... The prolonged DDR activates both ATM and ATR DNA damage kinases. The phosphorylation cascade initiated by these two kinases ...
Mechanism of Action and Clinical Impact of This Selective Cyclin-Dependent Kinase 4/6 Inhibitor in Various Solid Tumors". ... 4 (4): 308-321. doi:10.1107/s2052252517009241. ISSN 2052-2525. PMC 5571795. PMID 28875019. Tripathy, Debu; Bardia, Aditya; ... doi:10.1016/0022-0248(91)90859-4. ISSN 0022-0248. Giegé, Richard (December 2013). "A historical perspective on protein ...
This result suggest that there may be a mechanism of action other than inhibition of a cyclin-dependent kinase. After oral ... Like the related drugs palbociclib and ribociclib, abemaciclib inhibits the enzymes cyclin-dependent kinase 4 (CDK4) and cyclin ... dependent kinase 6 (CDK6). These enzymes are responsible for phosphorylating and thus deactivating the retinoblastoma protein, ... 17 (1): 80-4. doi:10.1016/j.cllc.2015.08.003. PMID 26432508. Llombart A, Toi M, Klise SR, Frenzel M, Chan EM, Sledge GW (30 ...
... cyclin dependent kinase 4) and Cdk6. Hop (HSP organizing protein) mediates the interaction between different HSPs, forming ... extracellular regulated kinase 5), or the checkpoint kinase Wee1. Cystic fibrosis (CF, mucoviscidosis) is a genetic disease ... "Canonical and kinase activity-independent mechanisms for extracellular signal-regulated kinase 5 (ERK5) nuclear translocation ... Yano M, Naito Z, Yokoyama M, Shiraki Y, Ishiwata T, Inokuchi M, Asano G (Mar 1999). "Expression of hsp90 and cyclin D1 in human ...
... may help protect bone marrow cells from damage caused by chemotherapy by inhibiting cyclin-dependent kinase 4/6, a ... Clinical trial number NCT03041311 for "Carboplatin, Etoposide, and Atezolizumab With or Without Trilaciclib (G1T28), a CDK 4/6 ... a CDK 4/6 Inhibitor, in Combination With Etoposide and Carboplatin in Extensive Stage Small Cell Lung Cancer (SCLC)" at ... ClinicalTrials.gov Clinical trial number NCT02514447 for "Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Patients With Previously ...
Malumbres M, Ortega S, Barbacid M. «Genetic analysis of mammalian cyclin-dependent kinases and their inhibitors.» Biol Chem ... Increasing Macrophage Adhesion via Cyclin-dependent Kinase 6." (2011) His scientific career has been awarded with prizes such ... "Genetic analysis of mammalian cyclin-dependent kinases and their inhibitors." (2000). "Toll-like Receptor-4 (TLR4) Down- ... Increasing Macrophage Adhesion via Cyclin-dependent Kinase 6.» J Biol Chem 2011 Jul 22; 286 (29): 25531-9.. ...
... 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 ...
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, is an inhibitor of cyclin D1/CDK4 and CDK6, and is used for the treatment of ...
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 ...
It plays a key role in regulating the cell cycle via protein-protein interactions with the cyclin-dependent kinase CDK4. It ... an oncoprotein found in complexes with cyclin-dependent kinase 4, a 19 S proteasomal ATPase regulator, and the tumor ... Karin M, Delhase M (Feb 2000). "The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling". ... "Gankyrin is an ankyrin-repeat oncoprotein that interacts with CDK4 kinase and the S6 ATPase of the 26 S proteasome". J. Biol. ...
CDKN2C, INK4C, p18, p18-INK4C, cyclin-dependent kinase inhibitor 2C, cyclin dependent kinase inhibitor 2C. ... CDKN2C‏ (Cyclin dependent kinase inhibitor 2C) هوَ بروتين يُشَفر بواسطة جين CDKN2C في الإنسان.[1][2][3] ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". مؤرشف من الأصل في 05 ديسمبر 2010.. الوسيط , ... negative regulation of cyclin-dependent protein serine/threonine kinase activity. • G1/S transition of mitotic cell cycle. • ...
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 ...
... a cyclin-dependent kinase inhibitor, exerts its effects by transcriptional inhibition in leukemia cell lines and patient ... an inhibitor of the cyclin dependent kinase CDK9, and 3) Study how the DNA intercalating agent psoralen interacts with genomic ... be attributed to the weaker signal obtained for bio-AT7519 or because AT7519 can bind and inhibit other cyclin-dependent kinase ... 9 (4): 920-8. doi:10.1158/1535-7163.MCT-09-1071. PMID 20354122. Tung, SY; Hong, JY; Walz, T; Moazed, D; Liou, GG (Feb 2012). " ...
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 ...
... cyclin-dependent kinase 4 inhibitor B and cyclin-dependent kinase inhibitor 2A, respectively. Both products act indirectly to ... The product of this protooncogene, proto-oncogene serine/threonine-protein kinase Pim-1, is indirectly involved in, and can ... 23 (3-4): 235-45. doi:10.3109/10428199609054826. PMID 9031104. Abbas O, Mahalingam M (February 2013). "The grenz zone". The ...
Inamoto S, Segil N, Pan ZQ, Kimura M, Roeder RG (November 1997). "The cyclin-dependent kinase-activating kinase (CAK) assembly ... specifically through transcriptional inhibition of cyclin-dependent kinase inhibitors such as p21. CRISPR-Cas9 knockout of the ... Gonzalez MI, Robins DM (March 2001). "Oct-1 preferentially interacts with androgen receptor in a DNA-dependent manner that ... Schoorlemmer J, Kruijer W (December 1991). "Octamer-dependent regulation of the kFGF gene in embryonal carcinoma and embryonic ...
de 2002). «Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4». Mol. Cell ... cyclins and cyclin dependent kinases». Oncogene (ENGLAND) 15 (2): 143-57. ISSN 0950-9232. PMID 9244350. doi:10.1038/sj.onc. ... a b «Entrez Gene: CDK2 cyclin-dependent kinase 2». *↑ Berthet C, Aleem E, Coppola V, Tessarollo L, Kaldis P (octubre de 2003). ... de 1994). «KAP: a dual specificity phosphatase that interacts with cyclin-dependent kinases». Proc. Natl. Acad. Sci. U.S.A. ( ...
"Cyclin Dependent Kinases and Cell Cycle Control" (PDF). nobelprize.org. Retrieved 4 June 2015. "Robert G. Edwards - ... Retrieved 4 June 2015. "Sir Edward Appleton (1892 - 1965)". BBC. Retrieved 4 June 2015. "Sir Edward Victor Appleton". Edinburgh ... Retrieved 4 June 2015. "Sir Alexander Fleming - Biographical". Nobel Foundation. Retrieved 1 June 2015. McGrath, Alister E. (1 ... Retrieved 4 June 2015. "Lord Todd - Biographical". Nobel Foundation. Retrieved 2 June 2015. "Peter Mitchell - Biographical". ...
SKP2 targets p27Kip-1, an inhibitor of cyclin-dependent kinases (CDKs). CDKs2/4 partner with the cyclinsE/D, respectively, ... This is achieved by continuous control of cyclins/CDKs levels through ubiquitination and degradation. When cyclin E is ... The level of cyclins, as the name suggests, are high only at certain time point during cell cycle. ... Moreover, ubiquitination can also act to turn on/off the kinase activity of a protein. The critical role of phosphorylation is ...
SLBP are marked for degradation by phosphorylation at two threonine residues by cyclin dependent kinases, possibly cyclin A/ ... 85 (4): 435-43. doi:10.1139/o07-057. PMID 17713579.. *^ a b c d e f g h Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z ... "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 ...
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 ... Section 4. Intrinsic X-Ray Fluorescence". In Bani, Lucia (Ed.). Metallomics and the Cell. Metal Ions in Life Sciences. 12. ... ISBN 978-94-007-5560-4.. CS1 maint: Extra text: editors list (link) electronic-book ISBN 978-94-007-5561-1 ISSN 1559-0836 ... 4] 19 years later, Rudolf Virchow contributed to the cell theory, arguing that all cells come from the division of preexisting ...
... , 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 ... 14 (4): e1006101. doi:10.1371/journal.pcbi.1006101. PMID 29659563.. *^ Woese CR, Olsen GJ, Ibba M, Söll D (March 2000). " ... 280 (4): 2405-8. doi:10.1074/jbc.C400431200. PMID 15579907.. *^ Kawahara A, Stainier DY (August 2009). "Noncanonical activity ... 108 (4): 1415-20. doi:10.1073/pnas.1011275108. PMID 21220307.. *^ Guo M, Schimmel P (March 2013). "Essential nontranslational ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ...
... preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase ... Produkowany jest przez różne rodziny, m.in.: jasnotowate (bazylia[4], mięta[5]), wawrzynowate[6] (wawrzyn, cynamon) i rutowate ... DOI: 10.1007/s10886-010-9857-4. PMID: 20838885. *↑ M. Govindarajan, R. Sivakumar, M. Rajeswary, K. Yogalakshmi. Chemical ... Meat Sci". 92 (4), s. 667-674, 2012. DOI: 10.1016/j.meatsci.2012.06.019. PMID: 22789458. ...
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 ... 4 (6213): 6213. doi:10.1038/srep06213. PMC 4148660. PMID 25169063.. *^ a b c d Ramanathan SP, Helenius J, Stewart MP, Cattin CJ ...
"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]. ... 4][12] Intracranial aneurysms occur more in women, by a ratio of 3 to 2, and are rarely seen in pediatric populations.[4][9] ...
"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 ... "DNA Gyrase: Structure and Function"। Critical Reviews in Biochemistry and Molecular Biology। 26 (3-4): 335-375। আইএসএসএন 1040- ...
... 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 ... 23 (4): 313-20. doi:10.1006/cbir.1998.0247. PMID 10600240.. *^ Gao T, Newton AC (August 2002). " ... HSPH2-4 are proposed names and the current name is linked:[22] ... 4][5] This was later described as the "Heat Shock Response" and ...
Jiang MC, Liao CF, Tai CC (June 2002). "CAS/CSE 1 stimulates E-cadhrin-dependent cell polarity in HT-29 human colon epithelial ... "Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes". The Journal of Cell Biology. 128 (5): ... Laoukili J, Alvarez-Fernandez M, Stahl M, Medema RH (September 2008). "FoxM1 is degraded at mitotic exit in a Cdh1-dependent ... The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein composed of five extracellular cadherin repeats, a ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... 1omw: Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and ... Buhl AM, Osawa S, Johnson GL (1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human ... 2bcj: Crystal Structure of G Protein-Coupled Receptor Kinase 2 in Complex with Galpha-q and Gbetagamma Subunits ...
Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bad (a Bcl-2 ... Caspases are proteins that are highly conserved, cysteine-dependent aspartate-specific proteases. There are two types of ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... 4 (1). doi:10.15347/wjm/2017.008.. *^ a b Tixeira R, Caruso S, ... In order to be released, the protein is cleaved by a calcium-dependent calpain protease. ...
A prominent kinase is cyclin-dependent kinase (or CDK), which comprises a sub-family of protein kinases. As their name implies ... "Biochemical characterization of the human cyclin-dependent protein kinase activating kinase. Identification of p35 as a novel ... CDKs are heavily dependent on specific cyclin molecules for activation. Once combined, the CDK-cyclin complex is capable of ... Herbst EA, MacPherson RE, LeBlanc PJ, Roy BD, Jeoung NH, Harris RA, Peters SJ (Jan 2014). "Pyruvate dehydrogenase kinase-4 ...
GTP-dependent protein binding. • GTPase activity. • mitogen-activated protein kinase kinase kinase binding. • protein binding. ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... "The MAP kinase kinase kinase MLK2 co-localizes with activated ... protein kinase binding. • nucleotide binding. • GTP binding. • identical protein binding. Cellular component. • cytoplasm. • ... regulation of protein kinase activity. • regulation of attachment of spindle microtubules to kinetochore. • regulation of small ...
... 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 ... 4]​ Posteriormente, fue caracterizado como un precursor proteico de gran tamaño (de unos 390 aminoácidos) que era procesado por ...
... 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 ... 4 *^ a b c d e f g Andreas Holzenburg, Elke Bogner. 2002. Structure-function relationships of human pathogenic viruses. New ... AIDS 17 Suppl 4, S25-S34 PMID 15080177. *Thomson, M. M., Perez-Alvarez, L. and Najera, R. (2002) Molecular epidemiology of HIV- ... Hanya saja prevalensi di Indonesia hanya 0,43 persen atau masih di bawah tingkat epidemi sebesar satu persen.[4] ...
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 ( ... 38 (4): 621-33. doi:10.1093/icb/38.4.621. JSTOR 4620189.. *^ a b c d e f g h Freeman, Gary; Lundelius, Judith W. (1992). " ... cdk). The complex Cyclin B/CDK1 a.k.a. MPF (maturation promoting factor) promotes entry into mitosis. ...
protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. Sci. U.S. ... cyclin binding. • cyclin-dependent protein serine/threonine kinase activity. • macromolecular complex binding. ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ...
1995). "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. ... "Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... "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 ...
Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product.. Soni R1, Muller L, Furet P, Schoepfer ... cyclin dependent kinase 4 - data and references - Guide to Pharmacology. Miscellaneous. *NCI CPTC Antibody Characterization ... Cyclin-Dependent Kinases/antagonists & inhibitors*. *Cyclin-Dependent Kinases/chemistry. *Cyclin-Dependent Kinases/metabolism ... based on the crystal structure of Cdk2 suggests that fascaplysin inhibits Cdk4 by binding to the ATP pocket of the kinase. ...
Cyclin dependent kinase 4Imported. ,p>Information which has been imported from another database using automatic procedures.,/p ... tr,Q9JKW8,Q9JKW8_MOUSE Cyclin dependent kinase 4 (Fragment) OS=Mus musculus GN=CDK4 PE=4 SV=1 ... IPR011009. Kinase-like_dom_sf. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. ... IPR011009. Kinase-like_dom_sf. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. ...
A dominant-negative cyclin D1 mutant prevents nuclear import of cyclin-dependent kinase 4 (CDK4) and its phosphorylation by CDK ... Concurrent overexpression of cyclin D1 and cyclin-dependent kinase 4 (Cdk4) in intestinal adenomas from multiple intestinal ... mice is associated with increased cyclin D1 and cyclin-dependent kinase 4 expression. Zhang, T., Nanney, L.B., Peeler, M.O., ... Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. ...
Compounds targeting complexes between cyclin-dependent kinases (CDKs) and cyclins (Cy) and inhibiting their activity are ... quinazoline-3-carboxamides as multi-cyclin-dependent kinase inhibitors.. Traquandi G1, Ciomei M, Ballinari D, Casale E, Colombo ... An expansion of pyrazolo[4,3-h]quinazoline chemical class oriented to the development of three points of variability was ...
It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE ... Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. ... Cyclin D-Dependent Kinase CDK4; PSK-J3 Kinase; p34PSK-J3 Kinase; Cdk4 Cyclin Dependent Kinase; Cyclin D Dependent Kinase CDK4; ... Protein Kinases: 9706*Protein-Serine-Threonine Kinases: 1353*Cyclin-Dependent Kinases: 639*Cyclin-Dependent Kinase 4: 285* ...
Data mining in the public domain demonstrates that cyclin-dependent kinase 4 ( CDK4) is highly expressed in nasopharyngeal ... carcinomas (NPC). Associated with cyclin-D, CDK4 phosphorylates and... ... Overexpression of G1-S cyclins and cyclin-dependent kinases during multistage human pancreatic duct cell carcinogenesis. Clin ... Molven A. CDK4 (cyclin-dependent kinase 4). Atlas Genet Cytogenet Oncol Haematol. 2007;11:117-8.Google Scholar ...
HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR N-[4-(2,4-Dimethyl-thiazol-5-yl)pyrimidin-2-yl]-N- ... Chain A: Cell division protein kinase 2. Chain Downloadable Files. Download FASTA File. View Sequence & DSSP Image. Download ...
HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR 4-[4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-ylamino]- ... pyrimidin-2-ylamines as moderately potent inhibitors of cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analogue program was ... pyrimidin-2-ylamines as moderately potent inhibitors of cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analogue program was ... Cell division protein kinase 2. A. 298. Homo sapiens. Mutation(s): 0 Gene Names: CDK2, CDKN2. EC: 2.7.1 (PDB Primary Data), 2.7 ...
A Open Label Study of the Efficacy and Safety of PD0332991 a Selective Inhibitor of the Cyclin Dependent Kinases 4 and 6 in ... A Open Label Phase II Study of the Efficacy and Safety of PD0332991 a Selective Inhibitor of the Cyclin Dependent Kinases 4 and ... Time Frame: 4 weeks ]. CA125 response is defined as ≥ 50% decrease from the baseline CA125 level and confirmed ≥ 21 days after ... Time Frame: 4 weeks ]. Toxicity of PD0332991 will be graded using the NCI Common Toxicity Criteria, version 3.0 ...
Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) ... Produktinformationen "Anti-cdk4, p34 (Cyclin-dependent Kinase 4)" Protein function: Ser/Thr-kinase component of cyclin D-CDK4 ( ... Anti-CDK4, Anti-PSK-J3, EC=2.7.11.22, Anti-Cyclin-dependent kinase 4, Anti-Cell division protein kinase 4. ... Protein function: Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and... mehr ...
The cyclin-dependent kinase 6/cyclin D2 partnership preferentially promotes multiple myeloma progression. cdk6 and cyclin D2 ... cyclins and cyclin-dependent kinases (cdk)] on one hand and cdk inhibitors (CKI) on the other (ref. 2; Fig. 1A). D cyclins are ... p18INK4C is not increased, and p27Kip1 is sequestered by cyclin D2 and cyclin-dependent kinase 6 in myeloma cells. cdk4 and ... Phosphorylation of retinoblastoma protein by cyclin-dependent kinase 6/cyclin D2 in discrete bone marrow foci. Sequential ...
Cyclin D1/Cyclin-Dependent Kinase 4 Interacts with Filamin A and Affects the Migration and Invasion Potential of Breast Cancer ... Cyclin D1/Cyclin-Dependent Kinase 4 Interacts with Filamin A and Affects the Migration and Invasion Potential of Breast Cancer ... Cyclin D1/Cyclin-Dependent Kinase 4 Interacts with Filamin A and Affects the Migration and Invasion Potential of Breast Cancer ... Cyclin D1/Cyclin-Dependent Kinase 4 Interacts with Filamin A and Affects the Migration and Invasion Potential of Breast Cancer ...
Hall M, Peters G. Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Adv Cancer Res ... reduction of cyclin D expression through antisense technology causes a concomitant decline in cyclin D-dependent kinase ... Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice. Nat Genet 2003;35:25-31. ... Cyclin-dependent kinase modulators studied at the NCI: pre-clinical and clinical studies. Curr Med Chem Anti-Canc Agents 2003;3 ...
Mitogen-activated protein kinase-activated protein kinase 1a. 8.0. Mitogen-activated protein kinase-activated protein kinase 2 ... Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. ... Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts ... Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts ...
Inhibitory activity against Cyclin D1-cyclin-dependent kinase 4 by measuring the phosphorylation of RbING. ...
Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inh Articles of Interest ... Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inh ... Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inh ... Re: Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 ...
A dominant-negative cyclin D1 mutant prevents nuclear import of cyclin-dependent kinase 4 (CDK4) and its phosphorylation by CDK ... A dominant-negative cyclin D1 mutant prevents nuclear import of cyclin-dependent kinase 4 (CDK4) and its phosphorylation by CDK ... A dominant-negative cyclin D1 mutant prevents nuclear import of cyclin-dependent kinase 4 (CDK4) and its phosphorylation by CDK ... A dominant-negative cyclin D1 mutant prevents nuclear import of cyclin-dependent kinase 4 (CDK4) and its phosphorylation by CDK ...
Cyclin Dependent Kinase 4 (Cell Division Protein Kinase 4 or... ... Cell Division Protein Kinase 4 or PSK J3 or CDK4 or EC 2.7. ... 112 Pages Report] Check for Discount on Cyclin Dependent Kinase 4 ( ... Cyclin Dependent Kinase 4 (Cell Division Protein Kinase 4 or PSK J3 or CDK4 or EC 2.7.11.22) - Pipeline Review, H2 2017. ... Cyclin Dependent Kinase 4 (Cell Division Protein Kinase 4 or PSK J3 or CDK4 or EC 2.7.11.22) - Cyclin-dependent kinase 4 is an ...
Cyclin D1/cyclin-dependent kinase 4 (CDK4) promotes G1-S-phase transition, and CDK phosphorylation of Smad3 has been associated ... Cyclin-Dependent Kinase 4-Mediated Phosphorylation Inhibits Smad3 Activity in Cyclin D-Overexpressing Breast Cancer Cells. ... Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature 2004;430:226-31. ... Smad3 phosphorylation by cyclin-dependent kinases. Cytokine Growth Factor Rev 2006;17:9-17. ...
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): ...
Cell Division Protein Kinase 4 or PSK J3 or CDK4 or EC 2.7.11.22) pipeline Target constitutes close to 42 molecules. Out of ... Enquire before buying Cyclin Dependent Kinase 4 (Cell Division Protein Kinase 4 or PSK J3 or CDK4 or EC 2.7.11.22) - Drugs in ... Enquire before buying for Cyclin Dependent Kinase 4 (Cell Division Protein Kinase 4 or PSK J3 or CDK4 or EC 2.7.11.22) - Drugs ... Cyclin Dependent Kinase 4 (Cell Division Protein Kinase 4 or PSK J3 or CDK4 or EC 2.7.11.22) - Drugs in Development, 2021 * ...
You are here: Home Products by Molecule of Interest p16-INK4a (Cyclin-dependent kinase inhibitor 2A, Cyclin-dependent kinase 4 ... p16-INK4a (Cyclin-dependent kinase inhibitor 2A, Cyclin-dependent kinase 4 inhibitor A, CDK4I, p16INK4A, p16-INK4, Multiple ...
Rat Cyclin Dependent Kinase 4 ELISA Kit-NP_000066.1 (MBS2533543) product datasheet at MyBioSource, ELISA Kits ... Molecular Function: ATP binding; cyclin binding; cyclin-dependent protein kinase activity; cyclin-dependent protein kinase ... CDK4 elisa kit :: Rat Cyclin Dependent Kinase 4 ELISA Kit. Catalog #. MBS2533543 .mycenter { display: block; margin-left: auto ... Cellular Component: chromatin; cyclin-dependent protein kinase holoenzyme complex; cytosol; nuclear membrane; nucleolus; ...
We have found that the putative miR-107 target cyclin-dependent-kinase 6 (CDK6) expression is increased by TLR4 as a result of ... down-regulates microRNA-107 increasing macrophage adhesion via cyclin-dependent kinase 6, Journal of Biological Chemistry, 286 ... down-regulates microRNA-107 increasing macrophage adhesion via cyclin-dependent kinase 6. ... down-regulates microRNA-107 increasing macrophage adhesion via cyclin-dependent kinase 6.pdf (Published (publishers copy) - ...
cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) (abemaciclib , palbociclib , ribociclib) and interstitial lung ... Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) (abemaciclib , palbociclib , ribociclib) and interstitial lung ... cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) (abemaciclib , palbociclib , ribociclib) and interstitial lung ... cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) (abemaciclib , palbociclib , ribociclib) and interstitial lung ...
Because cyclin-dependent kinase 4/6 (CDK4/6) inhibitors prevent G1/S transition, we hypothesized that serum TK1 could be a ... Thymidine kinase 1 (TK1) is a cell cycle-regulated enzyme with peak expression in the S phase during DNA synthesis, and it is ... HER2-negative breast cancer enrolled in the NeoPalAna trial received an initial 4 weeks of anastrozole, followed by palbociclib ... Serum thymidine kinase 1 activity as a pharmacodynamic marker of cyclin-dependent kinase 4/6 inhibition in patients with early- ...
Immobilised cyclin-dependent kinase 4 fusion proteins and uses thereof. par Raspé, Eric ;Roger, Pierre P. ;Coulonval, Katia ; ... JNKs function as CDK4-activating kinases by phosphorylating CDK4 and p21 par Colleoni, Bianca , Paternot, Sabine , Pita, Jaime ... CDK4 T172 phosphorylation is central in a CDK7-dependent bidirectional CDK4/CDK2 interplay mediated by p21 phosphorylation at ... the puzzle of highly regulated activating phosphorylation of CDK4 versus constitutively active CDK-activating kinase. par ...
... is a specific inhibitor of cyclin-dependent kinases CDK4 and CDK6. CDK4 is a subunit of the protein kinase complex that is ... is a specific inhibitor of cyclin-dependent kinases CDK4 and CDK6. CDK4 is a subunit of the protein kinase complex that is ... Mouse monoclonal antibody to Cyclin-dependent kinase 4 inhibitor D [IMD-19]: IgG. ... Cyclin-dependent kinase 4 inhibitor D (CDKN2D) ... Recombinant human Cyclin-dependent kinase 4 inhibitor D. Clone ...
  • Compounds targeting complexes between cyclin-dependent kinases (CDKs) and cyclins (Cy) and inhibiting their activity are regarded as promising antitumor agents to complement the existing therapies. (nih.gov)
  • An expansion of pyrazolo[4,3-h]quinazoline chemical class oriented to the development of three points of variability was undertaken leading to a series of compounds able to inhibit CDKs both in vitro and in vivo. (nih.gov)
  • Cdks (cyclin-dependent kinases) are heteromeric serine/threonine kinases that control progression through the cell cycle in concert with their regulatory subunits, the cyclins. (genecards.org)
  • The division cycle of eukaryotic cells is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs). (nih.gov)
  • Compared with normal human fibroblasts, cells transformed with a variety of viral oncoproteins show striking changes in the subunit composition of the cyclin-dependent kinases (CDKs). (nih.gov)
  • In normal cells, CDKs exist predominantly in multiple quaternary complexes, each containing a CDK, cyclin, proliferating cell nuclear antigen and the p21 protein. (nih.gov)
  • The process of eukaryotic cell division may be broadly divided into a series of sequential phases termed Gl, S, G2 and M. Correct progression through the various phases of the cell cycle has been shown to be critically dependent upon the spatial and temporal regulation of a family of proteins known as cyclin dependent kinases (CDKs) and a diverse set of their cognate protein partners termed cyclins. (allindianpatents.com)
  • CDKs are cdc2 (also known as CDKl) homologous serine-threonine kinase proteins that are able to utilise ATP as a substrate in the phosphorylation of diverse polypeptides in a sequence dependent context. (allindianpatents.com)
  • Modulation of the expression levels, degradation rates, and activation levels of various CDKs and cyclins throughout the cell cycle leads to the cyclical formation of a series of CDK/cyclin complexes, in which the CDKs are enzymatically active. (allindianpatents.com)
  • Cyclin-dependent kinases (CDKs) and Cyclin D have been known to increase in aggressive thyroid cancer. (yonsei.ac.kr)
  • During cell-cycle progression, D-cyclins activate cyclin-dependent kinases (CDKs) 4/6 to inactivate Rb, permitting E2F1-mediated S-phase gene transcription. (aacrjournals.org)
  • p21CIP1 is a potent, tight-binding inhibitor of Cdks and can inhibit the phosphorylation of Rb by cyclin A-Cdk2, cyclin E-Cdk2, cyclin D1-Cdk4, and cyclin D2-Cdk4 complexes. (yeastgenome.org)
  • During this interval, growth stimulatory and growth inhibitory signals transduced from the extracellular environment converge on the cell cycle control machinery, the engine of which is driven by cyclins and cyclin-dependent kinases (CDKs) and opposed by CDK inhibitors ( 1 ). (pnas.org)
  • Cyclin-dependent kinases (cdks) are critical regulators of cell cycle progression and RNA transcription. (dana-farber.org)
  • The recent generation of mice wherein individual cyclins or their cognate CDKs have been eliminated from the mouse germline has revealed the potential for significant redundancy with regard to CDK function and substrate regulation. (pubmedcentralcanada.ca)
  • This is particularly evident when one considers the potential contribution of G1 cyclins and CDKs to neoplastic transformation and growth. (pubmedcentralcanada.ca)
  • Cyclins function as allosteric regulatory subunits for the cyclin-dependent kinases (CDKs). (pubmedcentralcanada.ca)
  • 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)
  • 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)
  • Identification of potent pyrazolo[4,3-h]quinazoline-3-carboxamides as multi-cyclin-dependent kinase inhibitors. (nih.gov)
  • Following the identification through virtual screening of 4-(2,4-dimethyl-thiazol-5-yl)pyrimidin-2-ylamines as moderately potent inhibitors of cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analogue program was initiated. (rcsb.org)
  • Here the synthetic chemistry, the structure-guided design approach, and the structure-activity relationships (SARs) that led to the discovery of 2-anilino-4-(thiazol-5-yl)pyrimidine ATP-antagonistic CDK2 inhibitors, many with very low nM K(i)s against CDK2, are reported. (rcsb.org)
  • By contrast, cyclin D2 and cdk6 are coordinately increased, thereby overriding the inhibition by cdk inhibitors p18 INK4c and p27 Kip1 and phosphorylating Rb in conjunction with the existing cdk4. (aacrjournals.org)
  • With the combo of Palbociclib plus the estrogen inhibitor it 20 months time to progression.This seems pretty dramatic evidence pointing to the fact that CyclinD 4/6 inhibitors are extremely effective drugs. (her2support.org)
  • Of the 3 commonly used CDK-4,6 inhibitors, Abemicliclib or versenio seems to have less severe neutropenia. (her2support.org)
  • 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)
  • PI3 kinase inhibitors are a class of drugs designed to interrupt PI3 kinase signals and stop the growth of cancer cells. (komen.org)
  • the cyclin D. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. (wikipedia.org)
  • 4-(Pyrazol-4-yl)-pyrimidines as Selective Inhibitors of Cyclin-Dependent Kinase 4/6. (astx.com)
  • 4-(Pyrazol-4-yl)-pyrimidines as Selective Inhibitors. (astx.com)
  • G 1 CDK2 and CDK4 kinase activities were increased in both normal and neoplastic tissues derived from mice lacking individual CDK inhibitors and were synergistically stimulated by the simultaneous loss of two CDK inhibitors. (asm.org)
  • Two families of cyclin-dependent kinase (CDK) inhibitors, totaling seven genes, have been identified in mammalian cells. (asm.org)
  • In addition, they "titrate" CDK inhibitors, such as kinase inhibitory protein-1 (p27 Kip1 ), into ternary complexes, thereby freeing cyclin E-CDK2 complexes from such constraint ( 1 , 11 - 16 ). (pnas.org)
  • We have also investigated the geldanamaycins, small-molecule inhibitors of hsp90, a cellular chaperone required for the proper folding of multiple kinases, including cdk4. (dana-farber.org)
  • Hsp90 inhibition may represent a promising strategy for EGFR mutant lung cancers that have acquired resistance to standard tyrosine kinase inhibitors.Another active area of investigation is in regulation of Aurora kinases, mitotic kinases that are frequently dysregulated in cancer. (dana-farber.org)
  • Cyclin D1 or D3 expression does not vary in the clinical course, but that alone is insufficient to promote cell cycle progression unless cyclin-dependent kinase 4 (cdk4) is also elevated, in the absence of cdk6, to phosphorylate the retinoblastoma protein (Rb). (aacrjournals.org)
  • Thus, cyclin D1 pairs exclusively with cdk4 and cdk6 pairs only with cyclin D2, although cyclin D2 can also pair with cdk4 in multiple myeloma cells. (aacrjournals.org)
  • In addition, cyclin D1- or cyclin D3-expressing multiple myeloma cells are uniformly distributed in the bone marrow, whereas cdk6-specific phosphorylation of Rb occurs in discrete foci of bone marrow multiple myeloma cells before proliferation early in the clinical course and is then heightened with proliferation and disease progression. (aacrjournals.org)
  • Mutually exclusive cdk4/cyclin D1 and cdk6/cyclin D2 pairing, therefore, is likely to be a critical determinant for cell cycle reentry and progression and may play a pivotal role in the expansion of self-renewing multiple myeloma cells. (aacrjournals.org)
  • It is required for cell cycle activation in response to physiologic signals, such as antigen ( 4 , 5 ), that lead to coordinated elevation of cyclin D2 and cdk4, and then cdk6 ( 6 ). (aacrjournals.org)
  • Thus, although neither cdk4 nor cdk6 is required for cell cycle progression or viability in mice ( 11 ), specific D cyclins, cdk4/6, and CKIs are required for B-cell physiologic functions, implying that perturbation of this balance is likely to underlie oncogenesis in the B lineage. (aacrjournals.org)
  • PD 0332991 is a highly specific inhibitor of cyclin-dependent kinase 4 (Cdk4) (IC 50 , 0.011 μmol/L) and Cdk6 (IC 50 , 0.016 μmol/L), having no activity against a panel of 36 additional protein kinases. (aacrjournals.org)
  • Progression through the G 1 -S phase requires phosphorylation of the retinoblastoma (Rb) protein by Cdk4 ( 7 , 8 ) or the highly homologous enzyme Cdk6 ( 9 , 10 ) in complex with their activating subunits, the D-type cyclins, D1, D2, or D3 ( 11 ). (aacrjournals.org)
  • Elevated activity of cyclin-dependent kinase 6 (cdk6), a pRB kinase, was detected in all five squamous cell carcinoma lines. (aacrjournals.org)
  • We have found that the putative miR-107 target cyclin-dependent-kinase 6 (CDK6) expression is increased by TLR4 as a result of the decrease in miR-107. (tcd.ie)
  • Cyclin-dependent kinase 4 inhibitor D (CDKN2D) is a specific inhibitor of cyclin-dependent kinases CDK4 and CDK6. (biosensis.com)
  • Cell division protein kinase 6 (CDK6) is an enzyme encoded by the CDK6 gene. (wikipedia.org)
  • This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor Retinoblastoma protein making CDK6 an important protein in cancer development. (wikipedia.org)
  • In mammalian cells, cell cycle is activated by CDK6 in the early G1 phase through interactions with cyclins D1, D2 and D3. (wikipedia.org)
  • However, in recent years, new evidence proved that the presence of CDK6 is not essential for proliferation in every cell type, the cell cycle has a complex circuitry of regulation and the role of CDK6 might be more important in certain cell types than in others, where CDK4 or CDK2 can act as protein kinases compensating its role. (wikipedia.org)
  • There are additional functions of CDK6 not associated with its kinase activity. (wikipedia.org)
  • The protein encoded by the p16INK4a inhibits formation of CDK-cyclin-D complexes by competitive binding of CDK4 and CDK6. (genome.jp)
  • Enzymes that regulate G 1 phase progression include CDK4 and CDK6, which can be activated through their association with any one of three D-type cyclins, and CDK2, which forms active holoenzyme complexes with cyclins E and A ( 2 , 3 ). (pnas.org)
  • Mitogens stimulate synthesis of D-type cyclins and their assembly with CDK4 or CDK6 ( 4 - 6 ). (pnas.org)
  • Abemaciclib is an antitumor agent and dual inhibitor of cyclin-dependent kinases 4 (CDK4) and 6 (CDK6) that are involved in the cell cycle and promotion of cancer cell growth in case of unregulated activity. (drugbank.ca)
  • D-type cyclins (D1, D2, and D3) are G1-specific cyclins that associate with CDK4 or CDK6, and promote restriction point progression during G1 phase ( Sherr, 1993 ). (pubmedcentralcanada.ca)
  • Molecular modelling based on the crystal structure of Cdk2 suggests that fascaplysin inhibits Cdk4 by binding to the ATP pocket of the kinase. (nih.gov)
  • A, phosphorylation of Rb by cyclin D and cdk4/6 in early G 1 and cyclin E/cdk2 in late G 1 leads to the release of E2F and S-phase entry. (aacrjournals.org)
  • CDK4 T172 phosphorylation is central in a CDK7-dependent bidirectional CDK4/CDK2 interplay mediated by p21 phosphorylation at the restriction point. (ac.be)
  • This G1 arrest is associated with a dramatic decrease in the protein levels of Cdk2 and cyclin E correlated with an inhibition of the Cdk2 kinase activity. (biomedsearch.com)
  • The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. (springer.com)
  • The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has been implicated in the control of the G1 to S phase transition in mammals. (yeastgenome.org)
  • CIP1 encodes a novel 21 kd protein that is found in cyclin A, cyclin D1, cyclin E, and Cdk2 immunoprecipitates. (yeastgenome.org)
  • Activation of the MEK1/ERK pathway neither triggered degradation of the CDK inhibitor kinase inhibitory protein-1 (p27 Kip1 ) nor led to activation of cyclin E- and A-dependent CDK2, and such cells did not enter the DNA synthetic (S) phase of the cell division cycle. (pnas.org)
  • The cyclin E-CDK2 holoenzyme contributes to RB phosphorylation ( 17 - 19 ), phosphorylates p27 Kip1 to trigger its ubiquitin-mediated degradation ( 20 - 22 ), and likely modifies components of preinitiation complexes to trigger DNA replication per se ( 23 , 24 ). (pnas.org)
  • The irreversible decision to enter S phase, which is made at the so-called restriction point late in G 1 ( 28 ), therefore is marked by several molecular events, including ( i ) RB phosphorylation, ( ii ) p27 Kip1 degradation, ( iii ) initiation of cyclin A synthesis, and ( iv ) CDK2 activation ( 1 , 10 , 29 ). (pnas.org)
  • Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene . (wikipedia.org)
  • The protein encoded by this gene is a member of the Ser/Thr protein kinase family . (wikipedia.org)
  • This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product ( Rb ). (wikipedia.org)
  • Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. (wikipedia.org)
  • However, the correlation of cyclin D1 overexpression with E2F target gene regulation or of cdk-dependent cyclin D1 activity with tumor development has not been identified. (aacrjournals.org)
  • The miR-107 sequence occurs in an intron within the sequence encoding the gene for Pantothenate kinase-1? (tcd.ie)
  • Efficient sequence specific gene silencing for cyclin-dependent kinase 4 is possible through the use of siRNA technology. (patentsencyclopedia.com)
  • CDK4 (Cyclin Dependent Kinase 4) is a Protein Coding gene. (genecards.org)
  • GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity . (genecards.org)
  • The PIK3CA gene helps control PI3 kinase enzyme activity. (komen.org)
  • The PI3 kinase inhibitor alpelisib (Piqray) is FDA-approved for the treatment of some metastatic breast cancers that have a PIK3CA gene mutation. (komen.org)
  • We have previously demonstrated that loss of one candidate gene at this locus, cyclin-dependent kinase inhibitor 2B (Cdkn2b), in mice promotes vascular SMC apoptosis and aneurysm progression. (jci.org)
  • The protein encoded by this gene is a member of the cyclin-dependent kinase, (CDK) family, which includes CDK4. (wikipedia.org)
  • The gene spans 231,706 base pairs and encodes a 326 amino acid protein with a kinase function. (wikipedia.org)
  • All 27 exons, intron-exon boundaries, and essential promoter region of RB1 gene were then sequenced in genomic DNA from 4 pituitary adenomas with allelic imbalance on 13q14 including one adenoma without pRb expression and 3 adenomas with pRb expression. (tokushima-u.ac.jp)
  • Any somatic mutations, insertions, or microdeletions in the RB1 gene were not detected in 4 pituitary adenomas. (tokushima-u.ac.jp)
  • Therefore, the MEK/ERK pathway not only acts transcriptionally to induce the cyclin D1 gene but functions posttranslationally to regulate cyclin D1 assembly with CDK4 and to thereby help cancel p27 Kip1 -mediated inhibition. (pnas.org)
  • Gene products that coordinate S phase entry include cyclin A, which is induced in late G 1 and is essential for DNA synthesis ( 25 - 27 ). (pnas.org)
  • Cell division protein kinase 8 is an enzyme that in humans is encoded by the CDK8 gene . (wikipedia.org)
  • The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. (wikipedia.org)
  • Overexpression of cyclin D1 reduced STAT3-dependent gene expression in a dose-dependent manner. (sciencemag.org)
  • Cyclin D1 belongs to a family of proteins that regulate progression through the G 1 -S phase of the cell cycle by binding to cyclin-dependent kinase (cdk)-4 to phosphorylate the retinoblastoma protein and release E2F transcription factors for progression through cell cycle. (aacrjournals.org)
  • CDK4 in complexes with mutant cyclin D1 (T156A or T156E but not T156S) is not phosphorylated by recombinant CDK-activating kinase (CAK) in vitro, fails to undergo activating T-loop phosphorylation in vivo, and remains catalytically inactive and unable to phosphorylate the retinoblastoma protein. (asm.org)
  • p16 seems to act in a regulatory feedback circuit with CDK4, D-type cyclins and retinoblastoma protein. (nih.gov)
  • Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. (curehunter.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)
  • Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation. (springer.com)
  • Newly synthesized cyclin D1 assembled with cyclin-dependent kinase-4 (CDK4) to form holoenzyme complexes that phosphorylated the retinoblastoma protein inefficiently. (pnas.org)
  • In contrast, zinc induction of active MEK1 in cells also engineered to ectopically overexpress cyclin D1 and CDK4 subunits generated levels of cyclin D-dependent retinoblastoma protein kinase activity approximating those achieved in cells stimulated by serum. (pnas.org)
  • Cyclin D-CDK complexes phosphorylate the retinoblastoma protein (RB) ( 4 , 5 , 7 - 9 ), helping to cancel its growth suppressive function by eliminating its ability to function as a transcriptional corepressor ( 10 ). (pnas.org)
  • [5] Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. (wikipedia.org)
  • Cyclin D-CDK4 complexes are major integrators of various mitogenic and antimitogenic signals. (wikipedia.org)
  • Protein function: Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and. (biomol.com)
  • Protein function: Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. (biomol.com)
  • The first repeat makes direct contact with cyclin-dependent kinase (CDK) subunits in assembled holoenzyme complexes, whereas the second does not contribute directly to the CDK interface. (asm.org)
  • Although threonine 156 in mouse cyclin D1 is predicted to lie at the carboxyl terminus of the linker peptide that separates the two cyclin folds and is buried within the cyclin subunit, mutation of this residue to alanine has profound effects on the behavior of the derived cyclin D1-CDK4 complexes. (asm.org)
  • CAK phosphorylation is not required for nuclear transport of cyclin D1-CDK4 complexes, because complexes containing wild-type cyclin D1 and a CDK4 (T172A) mutant lacking the CAK phosphorylation site are efficiently imported. (asm.org)
  • In contrast, enforced overexpression of the CDK inhibitor p21Cip1 together with mutant cyclin D1 (T156A)-CDK4 complexes enhanced their nuclear localization. (asm.org)
  • These results suggest that cyclin D1 (T156A or T156E) forms abortive complexes with CDK4 that prevent recognition by CAK and by other cellular factors that are required for their nuclear localization. (asm.org)
  • These properties enable ectopically overexpressed cyclin D1 (T156A), or a more stable T156A/T286A double mutant that is resistant to ubiquitination, to compete with endogenous cyclin D1 in mammalian cells, thereby mobilizing CDK4 into cytoplasmic, catalytically inactive complexes and dominantly inhibiting the ability of transfected NIH 3T3 fibroblasts to enter S phase. (asm.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)
  • Additionally, Smad3/4 complexes, along with the forkhead box O protein, bind promoters responsible for transcription of p15 and p21 ( 10 ). (aacrjournals.org)
  • The complexes formed by CDK4 and the D-type cyclins have been strongly implicated in the control of cell proliferation during the G1 phase. (nih.gov)
  • Here we have investigated the significance of this phenomenon by molecular cloning of p21 and in vitro reconstitution of the quaternary cell-cycle kinase complexes. (nih.gov)
  • Importantly, these C-CDK complexes act as a kinase, phosphorylating and inactivating the protein of Rb and p-Rb related "pocket proteins" p107 and p130. (wikipedia.org)
  • Thus, although the activity of p27 Kip1 normally is canceled through a serum-dependent degradative process, overexpressed cyclin D1-CDK complexes sequestered p27 Kip1 and reduced the effective inhibitory threshold through a stoichiometric mechanism. (pnas.org)
  • Involvement of p38 mitogen-activated protein kinase in basic fibroblast growth factor-induced interl. (biomedsearch.com)
  • 13 Moreover, mitogen-activated protein kinase (MAPK) signal transduction pathways are evolutionarily conserved among eukaryotes and have been implicated as having key roles in a number of biological processes, including cell growth, differentiation, apoptosis, inflammation and responses to environmental stresses. (nature.com)
  • A constitutively active form of mitogen-activated protein kinase kinase (MEK1) was synthesized under control of a zinc-inducible promoter in NIH 3T3 fibroblasts. (pnas.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 p16 INK4a . (wikipedia.org)
  • Moreover, the expression of p21 and MMP1 genes were reduced by embelin in H 2 O 2 -treated HDFs in a dose-dependent manner. (springer.com)
  • However, COL1A1 genes were increased by embelin in H 2 O 2 -treated HDFs in a dose-dependent manner. (springer.com)
  • Methylation sensitive (MS)-polymerase chain reaction (PCR) and bisulfite sequencing analysis revealed hypomethylated status of CpG islands in the promoter region of the RB1 genes of 4 pituitary adenomas. (tokushima-u.ac.jp)
  • Studies of variations of the cyclin-dependent kinase inhibitor 1C and the cyclin-dependent kinase 4 genes in relation to type 2 diabetes mellitus a. (cdc.gov)
  • LEE011 dose-dependently inhibited RB phosphorylation and also decreased the expressions of its target genes such as FOXM1, Cyclin A1, and Myc in ATC. (yonsei.ac.kr)
  • The presence of two families of seven distinct mammalian cyclin-dependent kinase (CDK) inhibitor genes is thought to mediate the complexity of connecting a variety of cellular processes to the cell cycle control pathway. (asm.org)
  • Conceptually, genes that negatively regulate the growth-suppressing activity of either p53 or pRb may be proto-oncogenes, as exemplified by the observation that MDM2 ( 26 ) and cyclin D1 ( 20 ), negative regulators of p53 and pRb, respectively, are frequently activated in human cancers and promote tumor growth when targeted for transgenic expression in mouse mammary tissues ( 22 , 35 ). (asm.org)
  • Expression and amplification of cyclin genes in human breast cancer. (springer.com)
  • The INK4 family of CKIs (p16, p15, p18, and p19) inhibits cdk4/6 and the Cip/Kip family of CKIs (p21, p27, and p57) inhibits cyclin E/cdk 2. (aacrjournals.org)
  • Here we report the isolation of a human p16 complementary DNA and demonstrate that p16 binds to CDK4 and inhibits the catalytic activity of the CDK4/cyclin D enzymes. (nih.gov)
  • We find that p21 inhibits the activity of each member of the cyclin/CDK family. (nih.gov)
  • Lactoferrin inhibits G1 cyclin-dependent kinases during growth arrest of human breast carcinoma cells. (biomedsearch.com)
  • it inhibits the cyclin-dependent kinase (CDK) 4 and 6. (medindia.net)
  • The latest report Cyclin Dependent Kinase 4 - Pipeline Review, H2 2017, outlays comprehensive information on the Cyclin Dependent Kinase 4 (Cell Division Protein Kinase 4 or PSK J3 or CDK4 or EC 2.7.11.22) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (reportsnreports.com)
  • Furthermore, this report also reviews key players involved in Cyclin Dependent Kinase 4 (Cell Division Protein Kinase 4 or PSK J3 or CDK4 or EC 2.7.11.22) targeted therapeutics development with respective active and dormant or discontinued projects. (reportsnreports.com)
  • The frequency of these alterations alone clearly implies that abrogation of the G 1 checkpoint or acceleration of the Cdk4/cyclin D pathway provides a distinct advantage to cancer cells in terms of proliferation and perhaps survival. (aacrjournals.org)
  • Inhibition of linc-UFC1 resulted in cell proliferation inhibition and G1 cell cycle arrest, which was mediated by cyclin D1, CDK4, Rb and phosphorylated Rb. (nature.com)
  • Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor-positive (ER + ) breast cancer. (elsevier.com)
  • Silencing of APE1 attenuated cyclin D1/cyclin-dependent kinase 4 expression and phosphorylation of ERK1/2 and Akt, thereby affecting keratinocyte proliferation. (jimmunol.org)
  • Modern molecular methods, including genetic markers, cytokines, proliferation indexes, and cyclins, are all undergoing study to help determine which atypical moles may progress to melanoma, although no single marker has been determined. (medscape.com)
  • p19ARF counters uncontrolled proliferation and oncogenic signals in p53 dependent pathways. (novusbio.com)
  • It follows that overexpression of cyclin D has been found in aggressive breast cancers, and this overexpression is associated with a poor prognosis. (aacrjournals.org)
  • Although cyclin D1 overexpression is clearly implicated in the affected cancers, overexpression of cyclin D1 is not sufficient to drive oncogenic transformation. (pubmedcentralcanada.ca)
  • We also identify many proteins related to cytoskeletal function, biomolecular synthesis, organelle biogenesis, and calcium regulation whose levels of expression change concomitant with decreased cell motility induced by decreased cyclin D1 and cyclin D1-cdk4/6 activities. (aacrjournals.org)
  • DI-fusion Immobilised cyclin-dependent kinase 4 fusion proteins and. (ac.be)
  • It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. (wikipedia.org)
  • Cyclins are a family of proteins characterised by a homology region, containing approximately 100 amino acids, termed the "cyclin box" which is used in binding to, and defining selectivity for, specific CDK partner proteins. (allindianpatents.com)
  • Cyclin-dependent kinase 4 (CDK4) is known to be a 33 kD protein that drives G1 phase progression of the cell cycle by binding to a CCND protein to phosphorylate RB proteins. (umn.edu)
  • ZO proteins belong to the large family of membrane-associated guanylate kinase (MAGUK)-like proteins comprising a number of subfamilies based on domain content and sequence similarity. (hindawi.com)
  • Moreover, ZO proteins also associate with gap junctions (GJs) by directly interacting with connexins [ 4 - 6 ], which points towards a general role of ZO proteins in intercellular adhesion and communication. (hindawi.com)
  • It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (wikipedia.org)
  • Associated with cyclin-D, CDK4 phosphorylates and inactivates retinoblastoma (Rb) protein family members and mediates progression through the G1- to the S-phase of the cell cycle. (springer.com)
  • The cyclin D-CDK4/6 complex is critical to cell cycle progression, as it induces phosphorylation inhibition of the Rb protein. (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)
  • This leads to increased expression of downstream signalling molecules and activity of protein kinases that promote the cell cycle progression and initiation of DNA replication. (drugbank.ca)
  • Unlike other cyclins that are periodically synthesized during cell cycle progression, expression and accumulation of D-cyclins are strongly dependent on extracellular mitogenic cues. (pubmedcentralcanada.ca)
  • Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. (wikipedia.org)
  • Raf-1 phosphorylates MAPK/ERK kinases (MEKs), which in turn activate ERKs and facilitate their nuclear translocation ( 37 ). (pnas.org)
  • Protein kinases may be characterized by their regulation mechanisms. (allindianpatents.com)
  • The redox-dependent action of APE1 may be involved in the regulation of gastric inflammation ( 5 ), LPS-mediated inducible NO synthase ( 6 ), and high-mobility group box (HMGB) 1-induced inflammatory responses ( 7 ). (jimmunol.org)
  • Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase. (springer.com)
  • Several observations implicate the Ras/ERK signaling pathway in cyclin D1 regulation. (pnas.org)
  • Alterations in RD(INK4/ARF) -mediated en bloc regulation of the INK4-ARF locus in human squamous cell carcinoma of the head and neck. (osu.edu)
  • This review provides a brief overview of current data documenting various mechanisms underlying aberrant cyclin D1 regulation in human cancers and their impact on neoplastic transformation. (pubmedcentralcanada.ca)
  • Our understanding of mitogen-dependent cyclin D1 regulation is more advanced than that for cyclin D2 and D3. (pubmedcentralcanada.ca)
  • Human Cdk subunit 1 ( Cks1 ), as well as S-phase kinase-associated protein 2 ( Skp2 ), is an essential and specific factor in the p27 proteolysis by SCF Skp2 ubiquitin ligase. (aacrjournals.org)
  • This protein also contains an ATP-binding pocket, inhibitory and activating phosphorylation sites, a PSTAIRE-like cyclin-binding domain and an activating T-loop motif. (wikipedia.org)
  • This invention relates to pyrazole compounds that inhibit or modulate the activity of cyclin dependent kinases (CDK) and glycogen synthase kinase-3 (GSK-3), to the use of the compounds in the treatment or prophylaxis of disease states or conditions mediated by cyclin dependent kinases and glycogen synthase kinase-3, and to novel compounds having cyclin dependent kinase or glycogen synthase kinase-3 inhibitory or modulating activity. (allindianpatents.com)
  • Experimental evidence suggests that inhibition of cyclin D-dependent kinase activity may prevent tumor growth and/or at least partially revert the transformed phenotype. (aacrjournals.org)
  • For example, reduction of cyclin D expression through antisense technology causes a concomitant decline in cyclin D-dependent kinase activity and results in inhibition of tumor growth, abolition of tumorigenicity, or, in some instances, tumor cell death ( 24 -27 ). (aacrjournals.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)
  • This mutation can affect PI3 kinase and cause the tumor to grow. (komen.org)
  • Components of cyclinD1/cyclin-dependent kinase 4 (CDK4)/p16INK4a/pRb pathway are the frequent target of many tumor types. (tokushima-u.ac.jp)
  • This indicates that an increase in G 1 CDK kinase activity is a critical step during but is not sufficient for tumor growth. (asm.org)
  • 5 . A method according to claim 4 wherein the antigen is selected from the group consisting of tumor antigens, autoimmune antigens and an antigen isolated from a pathogenic organism. (google.com)
  • The cyclin D/Rb/E2F1 pathway was investigated in vitro using MCL cell lines and primary tumor cells. (aacrjournals.org)
  • Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (wikipedia.org)
  • We show that MDA-MB-231 motility is affected by disturbing cyclin D1 levels or cyclin D1-cdk4/6 kinase activity. (aacrjournals.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)
  • Elevated activity of cyclin-dependent kinase 6 in human squamous cell carcinoma lines -- Timmermann et al. (aacrjournals.org)
  • The activity of this kinase is restricted to the G1-S phase, which is controlled by the regu. (genecards.org)
  • Embelin decreased the SA-β-galactosidase activity in a dose-dependent manner in H 2 O 2 -treated HDFs. (springer.com)
  • It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18. (curehunter.com)
  • J:131845 Ciemerych MA, Yu Q, Szczepanska K, Sicinski P, CDK4 activity in mouse embryos expressing a single D-type cyclin. (jax.org)
  • Switching cyclin D-Cdk4 kinase activity on and off. (springer.com)
  • The protein synthesis inhibitor silvestrol has potent activity in B-cell leukemias via the mitochondrial pathway of apoptosis, and also reduces cyclin D1 expression in breast cancer and lymphoma cell lines. (aacrjournals.org)
  • We hypothesized that this dual activity of silvestrol would make it especially effective in malignancies driven by aberrant cyclin D1 expression. (aacrjournals.org)
  • In the cyclin D-CDK4-CDKN1B complex, this phosphorylation and consequent CDK4 enzyme activity, is dependent on the tyrosine phosphorylation state of CDKN1B. (abcam.com)
  • RAR-beta is a nuclear receptor that bears vitamin-A-dependent transcriptional activity. (genome.jp)
  • have found that cyclin D1, independent of cyclin-dependent kinase 4 (Cdk4) activity, can inhibit STAT3-mediated signaling. (sciencemag.org)
  • Ukoniq (umbralisib) is a dual inhibitor of phosphoinositide 3 kinase (PI3K). (drugs.com)
  • CDK4 exists, in part, as a multi-protein complex with a D-type cyclin, proliferating cell nuclear antigen and a protein, p21 (refs 7-9). (nih.gov)
  • 4 . A method according to any one of claims 1 to 3 wherein the antigen is a protein. (google.com)
  • 9 . A method according to claim 7 wherein the antigen is carcinoembryonic antigen (CEA) or modified CEA having the sequence shown in FIG. 3 (SEQ.ID.NO.:4). (google.com)
  • Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product. (nih.gov)
  • Moreover, when it is ectopically overexpressed in mammalian cells, cyclin D1 (T156A) assembles with CDK4 in the cytoplasm but is not imported into the cell nucleus. (asm.org)
  • Although cyclin D1 had no effect on STAT3 DNA binding, cyclin D1 did bind to the transcriptional activation domain of STAT3, suggesting a mechanism whereby STAT3-dependent transcription could be immediately attenuated. (sciencemag.org)
  • APC/C then drives the process forward as it subsequently targets Ase1 and cyclin B for destruction ( Peters 1999 ). (rupress.org)
  • Due to this property of D-cyclins, they are regarded as mitogenic sensors that relay signals from the extracellular environment to the core cell cycle machinery ( Sherr and Roberts, 1999 ). (pubmedcentralcanada.ca)
  • As a redox activator, APE1 regulates the activation of multiple cellular transcription factors, including NF-κB and hypoxia-inducible factor (HIF)-1α ( 1 , 3 , 4 ). (jimmunol.org)
  • Growth factor receptor tyrosine kinases activate a class of intracellular serine/threonine protein kinases termed mitogen-activated protein kinases (MAPKs) or extracellular signal-regulated kinases (ERKs) ( 30 , 31 ). (pnas.org)
  • Performing Western blotting, we found that RB phosphorylation and the expression of Cyclin D are significantly higher in papillary thyroid cancer (PTC) cell lines as well as anaplastic thyroid cancer (ATC) cell lines, compared with normal thyroid cell line and follicular thyroid cancer cell line. (yonsei.ac.kr)
  • Zinc treatment of serum-starved cells activated extracellular signal-regulated protein kinases (ERKs) and induced expression of cyclin D1. (pnas.org)
  • Coordinated expression of cyclin-dependent kinase-4 and its regulators in human oral tumors. (nih.gov)
  • The basis for this novel and specific cdk/D cyclin pairing lies in differential transcriptional activation. (aacrjournals.org)
  • CMGC Ser/Thr protein kinase family. (abcam.com)
  • A to D, designated tumors were implanted into nude mice as described in Fig. 4 and allowed to grow to ∼200 mg. (aacrjournals.org)
  • Ibrance capsules for oral administration contain 125 mg, 100 mg, or 75 mg of palbociclib, a kinase inhibitor. (rxlist.com)
  • At or below pH 4, palbociclib behaves as a high-solubility compound. (rxlist.com)
  • Sequence motifs have been identified that generally correspond to each of these kinase families (e.g. (allindianpatents.com)
  • Early work resulted in the identification of the individual cyclin-dependent kinases that are activated during distinct cell cycle phases and contributed to our understanding of how phosphorylation of downstream targets in turn contributes to regulated cell cycle transitions. (pubmedcentralcanada.ca)
  • Cyclin D1 which functions as a mitogenic sensor and allosteric activator of CDK4/6, is one of the more frequently altered cell cycle regulators in cancers. (pubmedcentralcanada.ca)
  • Conversely, c-myc overexpression can inhibit the Smad-dependent transcription of p15 and p21 ( 11 ). (aacrjournals.org)
  • The appropriate protein kinase functions in signalling pathways to activate or inactivate (either directly or indirectly), for example, a metabolic enzyme, regulatory protein, receptor, cytoskeletal protein, ion channel or pump, or transcription factor. (allindianpatents.com)
  • CDK8 and cyclin C associate with the mediator complex and regulate transcription by several mechanisms. (wikipedia.org)
  • Cyclin D1 is frequently overexpressed in cancers and its overexpression can be attributed to many factors including increased transcription, translation, and protein stability. (pubmedcentralcanada.ca)
  • Cyclin D1 expression and accumulation are induced by growth factors and occur at multiple levels including increased transcription, translation, and protein stability. (pubmedcentralcanada.ca)
  • A pathway from receptor kinases to ERKs sequentially involves the small GTP-binding protein Ras and the Raf-1 protein kinase ( 32 - 36 ). (pnas.org)
  • Potentially, the mutation of BRCA2 found in some tumors overexpressing cyclin D contributes to the inhibition of Smad3 cell cycle control in these cancers ( 25 ). (aacrjournals.org)
  • MBS2533543 is a ready-to-use microwell, strip plate Sandwich ELISA (enzyme-linked immunosorbent assay) Kit for analyzing the presence of the Cyclin Dependent Kinase 4 (CDK4) ELISA Kit target analytes in biological samples. (mybiosource.com)
  • PI3 kinase is an enzyme important in cell growth. (komen.org)
  • Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2. (expasy.org)
  • This work represents a first step toward defining tumors that are more likely to respond to Aurora kinase inhibition. (dana-farber.org)
  • We hypothesized that elevated cyclin D1 facilitates motility in the invasive MDA-MB-231 breast cancer cell line. (aacrjournals.org)
  • Based on these observations, cyclin D-dependent kinases have been considered for many years a prime target for cancer chemotherapy ( 22 , 23 ). (aacrjournals.org)
  • Rb inactivation in cell cycle and cancer: the puzzle of highly regulated activating phosphorylation of CDK4 versus constitutively active CDK-activating kinase. (ac.be)
  • Thus far, clearly identified types or causes of CRC are hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, inflammatory bowel diseases, human papillomavirus, and acquired immunodeficiency syndrome [ 4 ]. (hindawi.com)
  • However, there has been no study to investigate effects of a selective CDK 4/6 inhibitor, Ribociclib (LEE011), in thyroid cancer. (yonsei.ac.kr)
  • We will finally discuss how studies on phosphatidylinositol-3-kinase (PI3K) signalling, as the paradigmatic pro-tumoural signal downstream of oncogenic Kras in pancreatic cancer, would benefit from exploratory proteomics to increase the efficiency of targeted therapies. (mdpi.com)
  • Molecular Pathways: targeting the cyclin D-CDK4/6 axis for cancer treatment. (springer.com)
  • Stage 1 is almost normal, Stage 2 is larger and has more tissue, Stage 3 is darker and some cells are leaving to invade other areas, Stage 4 is where few glands are recognizable, and Stage 5 is unrecognizable glands (Prostate Cancer Stages). (smore.com)
  • We have demonstrated the depletion of cdk4 in lung cancer cell lines treated with geldanamycins, an effect that induces retinoblastoma-dependent G1 arrest. (dana-farber.org)
  • During the course of this work, we discovered that lung cancer cell lines harboring kinase domain mutations of epidermal growth factor receptor (EGFR) were the most sensitive to hsp90 inhibition, and we have defined mutant EGFR as a novel hsp90 client protein that is rapidly depleted following geldanamycin treatment. (dana-farber.org)
  • We have shown that the Aurora kinase inhibitor VX-680 induces endoreduplication and eventual cell death in cancer cells. (dana-farber.org)