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

Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. (1/363)

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)

Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (2/363)

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

Progesterone inhibits estrogen-induced cyclin D1 and cdk4 nuclear translocation, cyclin E- and cyclin A-cdk2 kinase activation, and cell proliferation in uterine epithelial cells in mice. (3/363)

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. (4/363)

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)

NF-kappaB function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase transition. (5/363)

Nuclear factor kappa B (NF-kappaB) has been implicated in the regulation of cell proliferation, transformation, and tumor development. We provide evidence for a direct link between NF-kappaB activity and cell cycle regulation. NF-kappaB was found to stimulate transcription of cyclin D1, a key regulator of G1 checkpoint control. Two NF-kappaB binding sites in the human cyclin D1 promoter conferred activation by NF-kappaB as well as by growth factors. Both levels and kinetics of cyclin D1 expression during G1 phase were controlled by NF-kappaB. Moreover, inhibition of NF-kappaB caused a pronounced reduction of serum-induced cyclin D1-associated kinase activity and resulted in delayed phosphorylation of the retinoblastoma protein. Furthermore, NF-kappaB promotes G1-to-S-phase transition in mouse embryonal fibroblasts and in T47D mammary carcinoma cells. Impaired cell cycle progression of T47D cells expressing an NF-kappaB superrepressor (IkappaBalphaDeltaN) could be rescued by ectopic expression of cyclin D1. Thus, NF-kappaB contributes to cell cycle progression, and one of its targets might be cyclin D1.  (+info)

Activation of cyclin A gene expression by the cyclin encoded by human herpesvirus-8. (6/363)

Human herpesvirus-8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, encodes a protein, referred to as HHV8-Vcyc, with sequence similarity to human G1 cyclins, in particular of the D type. HHV8-Vcyc is expressed in Kaposi's sarcoma and functional analysis suggests that it can activate cyclin-dependent kinases (cdk) and thereby trigger inactivation of the retinoblastoma protein (pRb), indicating that HHV8-Vcyc may contribute to the oncogenic potential of HHV-8. We show here that HHV8-Vcyc can activate transcription of the human cyclin A gene in quiescent cells, a property shared with known transforming oncogenes. Transcriptional activation by HHV8-Vcyc depends on an E2F-binding site in the cyclin A promoter, and cdk6 kinase activity is required. The ability of HHV8-Vcyc to activate cyclin A gene expression is shared by D-type cyclins and cyclin E. Unlike D-type cyclins, HHV8-Vcyc is unable to trigger phosphorylation of the pRb-related protein p107 and fails to induce dissociation of p107 from E2F. Unlike cyclin E, HHV8-Vcyc fails to interact physically with E2F complexes on the cyclin A promoter. These results provide additional evidence for the notion that the HHV-8-encoded cyclin differs in several properties from cellular G1 cyclins.  (+info)

Anchorage dependence of mitogen-induced G1 to S transition in primary T lymphocytes. (7/363)

Anchorage dependence defines the cellular requirement for integrin-mediated adhesion to substrate to initiate DNA replication in response to growth factors. In this study we investigated whether normal T cells, which spend extended periods in a nonadherent state, show similar requirements for cell cycle progression in response to TCR stimulation. Resting primary T lymphocytes were induced to enter the cell cycle by TCR triggering, and leukocyte integrins were either engaged using purified ICAM-1 or inhibited with function-blocking mAbs. Our data indicate that leukocyte integrins complement TCR-driven mitogenic signals not as a result of their direct clustering but, rather, via integrin-dependent organization of the actin cytoskeleton. Leukocyte integrin-dependent reorganization of the actin cytoskeleton cooperates with the TCR to effect mitogen-activated protein kinase activation, but also represents a required late (4-8 h poststimulation) component in the mitogenic response of normal T cells. Prolonged leukocyte integrin-dependent spreading, in the context of intercellular contact, is a requisite for the production of the mitogenic cytokine IL-2, which, in turn, is involved in the induction of D3 cyclin and is primarily responsible for the decrease in the cyclin-dependent kinase inhibitor p27kip, resulting in retinoblastoma protein inactivation and S phase entry. Thus, T lymphocytes represent a peculiar case of anchorage dependence, in which signals conveyed by integrins act sequentially with the activating stimulus to effect a sustained production of the essential mitogenic cytokine.  (+info)

CTLA-4-Mediated inhibition of early events of T cell proliferation. (8/363)

CTLA-4 engagement by mAbs inhibits, while CD28 enhances, IL-2 production and proliferation upon T cell activation. Here, we have analyzed the mechanisms involved in CTLA-4-mediated inhibition of T cell activation of naive CD4+ T cells using Ab cross-linking. CTLA-4 ligation inhibited CD3/CD28-induced IL-2 mRNA accumulation by inhibiting IL-2 transcription, which appears to be mediated in part through decreasing NF-AT accumulation in the nuclei. However, CTLA-4 ligation did not appear to affect the CD28-mediated stabilization of IL-2 mRNA. Further, CTLA-4 engagement inhibited progression through the cell cycle by inhibiting the production of cyclin D3, cyclin-dependent kinase (cdk)4, and cdk6 when the T cells were stimulated with anti-CD3/CD28 and with anti-CD3 alone. These results indicate that CTLA-4 signaling inhibits events early in T cell activation both at IL-2 transcription and at the level of IL-2-independent events of the cell cycle, and does not simply oppose CD28-mediated costimulation.  (+info)

As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
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
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Recombinant Cyclin-Dependent Kinase 10 (CDK10) Protein (His tag). Species: Cow (Bovine). Source: Yeast. Order product ABIN1616360.
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View mouse Cdk11b Chr4:155624854-155649938 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
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Phosphorylation of Sic1, a Cyclin-dependent Kinase (Cdk) Inhibitor, by Cdk Including Pho85 Kinase Is Required for Its Prompt Degradation: In the yeast Saccharom
Cdk14 - Cdk14 (Myc-DDK-tagged) - Mouse cyclin-dependent kinase 14 (Cdk14) available for purchase from OriGene - Your Gene Company.
1GIH: Crystallographic approach to identification of cyclin-dependent kinase 4 (CDK4)-specific inhibitors by using CDK4 mimic CDK2 protein.
pep:known chromosome:VEGA66:5:146231288:146302874:1 gene:OTTMUSG00000025856 transcript:OTTMUST00000063710 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Cdk8 description:cyclin-dependent kinase 8 ...
AZD5438 is a potent inhibitor of CDK1/2/9 with IC50 of 16 nM/6 nM/20 nM. It is less potent to CDK5/6 and also inhibits GSK3β. Phase 1.Quality confirmed by NMR & HPLC. See customer reviews, validations & product citations.
Looking for online definition of cyclin-dependent kinase 15 in the Medical Dictionary? cyclin-dependent kinase 15 explanation free. What is cyclin-dependent kinase 15? Meaning of cyclin-dependent kinase 15 medical term. What does cyclin-dependent kinase 15 mean?
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 ...
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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 ...
Cyclin-Dependent Kinase 6: Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.
The retinoblastoma tumor suppressor (Rb) acts in a conserved pathway that is deregulated in most human cancers. Inactivation of the single Rb-related gene in Caenorhabditis elegans, lin-35, has only limited effects on viability and fertility, yet causes changes in cell-fate and cell-cycle regulation when combined with inactivation of specific other genes. For instance, lin-35 Rb is a synthetic multivulva (synMuv) class B gene, which causes a multivulva phenotype when inactivated simultaneously with a class A or C synMuv gene. We used the ORFeome RNAi library to identify genes that interact with C. elegans lin-35 Rb and identified 57 genes that showed synthetic or enhanced RNAi phenotypes in lin-35 mutants as compared to rrf-3 and eri-1 RNAi hypersensitive mutants. Based on characterizations of a deletion allele, the synthetic lin-35 interactor zfp-2 was found to suppress RNAi and to cooperate with lin-35 Rb in somatic gonad development. Interestingly, ten splicing-related genes were found to function
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
A stable environment minimizes evapora- tive heat loss. 10. Cyclin-dependent kinases participate recomendaad death of neurons evoked by DNA- damaging agents. Daleiden, A.
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"MicroRNA-495 inhibits proliferation of glioblastoma multiforme cells by downregulating cyclin-dependent kinase 6". World J Surg ...
November 1999). "Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q ... Mantle cell lymphoma is excluded due to the lack of CD5 and cyclin-D1 expression. Clonal rearrangements of the immunoglobulin ... July 1998). "Absence of cyclin D1 protein expression in splenic marginal zone lymphoma". Mod. Pathol. 11 (7): 601-6. PMID ... 40 (6): 642-51. doi:10.1136/jcp.40.6.642. PMC 1141055 . PMID 3497180. Berger F, Felman P, Thieblemont C, et al. (March 2000). " ...
... has been shown to interact with Cyclin-dependent kinase 4 and Cyclin-dependent kinase 6. GRCh38: Ensembl release 89: ... 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 ...
Malumbres M, Ortega S, Barbacid M. «Genetic analysis of mammalian cyclin-dependent kinases and their inhibitors.» Biol Chem ... Toll-like Receptor-4 (TLR4) Down-regulates MicroRNA-107, Increasing Macrophage Adhesion via Cyclin-dependent Kinase 6.» J Biol ... 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- ...
There is evidence to suggest that miR-129 directly targets Cdk6, cyclin dependant kinase 6- a cell proliferation regulator. ... 2004). "Cell cycle-dependent transcriptional regulation of calmodulin-binding transcription activator 1 in neuroblastoma cells ... 24 (6): 1407-12. doi:10.3892/ijo.24.6.1407. PMID 15138581. Liao R, Sun J, Zhang L, Lou G, Chen M, Zhou D, et al. (2008). " ... doi:10.1016/S0960-9822(02)00809-6. PMID 12007417. Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T (2003). "New ...
Ishimi Y, Komamura-Kohno Y (2001). "Phosphorylation of Mcm4 at specific sites by cyclin-dependent kinase leads to loss of Mcm4, ... This gene is mapped to a region on the chromosome 8 head-to-head next to the PRKDC/DNA-PK, a DNA-activated protein kinase ... The phosphorylation of this protein by CDC2 kinase reduces the DNA helicase activity and chromatin binding of the MCM complex. ... A role for cdc2 kinase". J. Biol. Chem. 273 (27): 17095-101. doi:10.1074/jbc.273.27.17095. PMID 9642275. You Z, Komamura Y, ...
... abemaciclib inhibits the enzymes cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6). These enzymes are ... a CDK4/6 inhibitor, or placebo in first-line treatment of women with HR+, HER2-locoregionally recurrent or metastatic breast ...
Increases Proliferation via Cyclin-dependent Kinases". Journal of Biological Chemistry. 284 (36): 24223-24232. doi:10.1074/jbc. ... and suppresses apoptosis by regulating cyclin-dependent kinase 1 (Cdk-1). PFKFB3's synthesis of F2,6BP in the nucleus was found ... Expression of the promoter is shown to be induce by phorbol esters and cyclic-AMP-dependent protein kinase signaling. The four ... due to phosphorylation of Ser-460 by PKA or AMP-dependent protein kinase. The high '2-Kase' activity of PFKFB3 is also due to ...
Clb5 and Clb6 bind and activate Cdk1, and high levels of these cyclins are required for entering S-phase. S-phase cyclin ... G1/S cyclin-Cdk complexes promote the destruction of Sic1 and allow activation of Clb5- and Clb6-Cdk1 complexes. As the yeast ... In this hypothesis, cyclin concentrations must rise and accumulate to proceed to the next stage of the cell cycle. In mitotic ... Clb5 and Clb6 levels rise during G1 (earlier than other B-type cyclins) and stay high throughout S and M phases. During S-phase ...
Cyclin-dependent kinases (CDKs) 4 and 6 are enzymes that have been shown to promote cell division and multiplication in both ... Ribociclib (trade name Kisqali) is an inhibitor of cyclin D1/CDK4 and CDK6, and is used for the treatment of certain kinds of ... Combination CDK4/6 and ALK inhibition demonstrates on-target synergy against neuroblastoma". Cancer Research. 74 (19 Supplement ... selective small molecule inhibitor of CDK4/6- Reactivating Rb in cancer". Molecular Cancer Therapeutics. 12 (11_Supplement): ...
To this end, ViroStatics has focused on selectively targeting the Cyclin Dependent Kinases (CDKs) involved in these ... ViroStatics has discovered and is developing novel, highly potent inhibitors, which selectively target CDK4/6/9 in a single ... perturbations (CDK9 and CDK4/6). ViroStatics was formed In 2007 as a for-profit spin-off from the Research Institute for Human ...
... has also been shown to directly inhibits CDK6 (Cyclin-dependent kinase 6) expression and decreases the level of ... Voltage-dependent L-type calcium channel subunit beta-2), TSSK6 (Testis-Specific Serine Kinase 6), NT5DC2 (Cytosolic 5'- ... It was observed that miR-137 expression is lost in Ras-dependent pancreatic cancer, and that restoration of its expression ... Serine/threonine-protein kinase D3). Neault et al. recently identified miR-137 as a senescence effector miRNA induced by ...
... 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 ... "Mechanism of inhibition of proliferating cell nuclear antigen-dependent DNA synthesis by the cyclin-dependent kinase inhibitor ... "Entrez Gene: CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1)". Gartel AL, Radhakrishnan SK (May 2005). "Lost in ...
Cyclin D1, Cyclin-dependent kinase 7, DACH1, Death associated protein 6, L-DOPA, EFCAB6, Epidermal growth factor receptor, ... The AR acetylation site is a key target of NAD-dependent and TSA-dependent histone deacetylases and long non coding RNA. More ... "Cyclin D1 binds the androgen receptor and regulates hormone-dependent signaling in a p300/CBP-associated factor (P/CAF)- ... Kim J, Jia L, Stallcup MR, Coetzee GA (February 2005). "The role of protein kinase A pathway and cAMP responsive element- ...
Cyclin-dependent kinase 2, Cyclin-dependent kinase 6, FAM40A, IGBP1, MOBKL3, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R3B, PPP2R5A, ... Cheng A, Kaldis P, Solomon MJ (Nov 2000). "Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type 2C ... "Phosphorylation and activation of hamster carbamyl phosphate synthetase II by cAMP-dependent protein kinase. A novel mechanism ... Bennin DA, Don AS, Brake T, McKenzie JL, Rosenbaum H, Ortiz L, DePaoli-Roach AA, Horne MC (Jul 2002). "Cyclin G2 associates ...
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- ...
... is a gene that provides instructions for making a protein called cyclin-dependent kinase-like 5 also known as serine/ ... "Preclinical Program for Cyclin-Dependent Kinase-Like 5 (CDKL5) Deficiency". Amicus Therapeutics Press Release. 6 July 2016. ... Cyclin-dependent kinase Rett syndrome West syndrome GRCh38: Ensembl release 89: ENSG00000008086 - Ensembl, May 2017 GRCm38: ... The CDKL5 protein acts as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of ...
Jain SK, Bharate SB, Vishwakarma RA (2012). "Cyclin-dependent kinase inhibition by flavoalkaloids". Mini Rev Med Chem. 12 (7): ... Bose P, Simmons GL, Grant S (2013). "Cyclin-dependent kinase inhibitor therapy for hematologic malignancies". Expert Opin ... One example is alvocidib, a potent CDK9 kinase inhibitor that is being developed for the treatment of chronic lymphocytic ... 26 (6): 1844-1845. doi:10.1016/S0031-9422(00)82304-3. Zhen, J., Dai, Y., Villani, T., Giurleo, D., Simon, J. and Wu, Q., 2017. ...
... a cyclin-dependent kinase inhibitor, is dependent on p53 signaling". PLOS ONE. 8 (3): e59588. doi:10.1371/journal.pone.0059588 ... Fu W, Ma L, Chu B, Wang X, Bui MM, Gemmer J, Altiok S, Pledger WJ (Jun 2011). "The cyclin-dependent kinase inhibitor SCH 727965 ... Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. Dinaciclib ( ... Apoptosis of osteosarcoma cultures can be induced by the combination of the cyclin-dependent kinase inhibitor SCH727965 and a ...
... has been shown to interact with: AKAP8, CDC2L1, CDKN1B, CRABP2, Cyclin-dependent kinase 4, Cyclin-dependent kinase 6 ... Fink JR, LeBien TW (2001). "Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors". Exp. Hematol. ... Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which ... "Cyclin D- and E-dependent kinases and the p57(KIP2) inhibitor: cooperative interactions in vivo". Mol. Cell. Biol. 19 (1): 353- ...
... endothelin receptor A and cyclin dependent kinase inhibitor. Mutations in interleukin 6 may be protective.[citation needed]. ... 34 (6): 1398-1403. doi:10.1161/01.STR.0000073841.88563.E9. PMID 12775880. Campi, A; Ramzi N, Molyneaux AJ, Summers, PE, Kerr, ... 62 (6): 1187-202; discussion 1202-3. doi:10.1227/01.neu.0000333291.67362.0b. PMID 18824986. Mitchell P, Kerr R, Mendelow AD, ... The inflammatory mediators are: Interleukin 1 beta, Interleukin 6, Tumor necrosis factor alpha (TNF alpha), MMP1, MMP2, MMP9, ...
... by cyclin-dependent kinase 2-cyclin E and its role in centrosome duplication". The Journal of Biological Chemistry. 276 (24): ... This link between the cell cycle and the centrosome cycle is mediated by cyclin-dependent kinase 2 (Cdk2). There has been ample ... Matsumoto, Y; Hayashi, K; Nishida, E (Apr 22, 1999). "Cyclin-dependent kinase 2 (Cdk2) is required for centrosome duplication ... Lacey, KR; Jackson, PK; Stearns, T (Mar 16, 1999). "Cyclin-dependent kinase control of centrosome duplication". Proceedings of ...
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 ...
... like other cyclin-dependent kinases, contains a T-loop, which, in the absence of an interacting cyclin, prevents substrate ... E2F#E2F.2FpRb complexes Hyperphosphorylation cdc25 Maturation promoting factor CDK cyclin A cyclin B cyclin D cyclin E Wee ( ... Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that ... De Bondt HL, Rosenblatt J, Jancarik J, Jones HD, Morgan DO, Kim SH (June 1993). "Crystal structure of cyclin-dependent kinase 2 ...
"Entrez Gene: CDK10 cyclin-dependent kinase (CDC2-like) 10". Kasten M, Giordano A (Apr 2001). "Cdk10, a Cdc2-related kinase, ... Cyclin-dependent kinase 10 has been shown to interact with ETS2. GRCh38: Ensembl release 89: ENSG00000185324 - Ensembl, May ... This kinase has been shown to play a role in cellular proliferation. Its function is limited to cell cycle G2-M phase. At least ... Cell division protein kinase 10 is an enzyme that in humans is encoded by the CDK10 gene. The protein encoded by this gene ...
"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein ... Liu, Ji; Kipreos, Edward T. (2000). "Evolution of Cyclin-Dependent Kinases (CDKs) and CDK-Activating Kinases (CAKs): ... "Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK " ...
"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... Cyclin-dependent kinase 7 has been shown to interact with: Androgen receptor, Cyclin H, GTF2H1, MNAT1, P53, SUPT5H, and XPB. ... "Entrez Gene: CDK7 cyclin-dependent kinase 7 (MO15 homolog, Xenopus laevis, cdk-activating kinase)". Lee DK, Duan HO, Chang C ( ... Drapkin R, Le Roy G, Cho H, Akoulitchev S, Reinberg D (Jun 1996). "Human cyclin-dependent kinase-activating kinase exists in ...
"Entrez Gene: CDK3 cyclin-dependent kinase 3". Bullrich F, MacLachlan TK, Sang N, et al. (1995). "Chromosomal mapping of members ... 2002). "ik3-1/Cables is a substrate for cyclin-dependent kinase 3 (cdk 3)". Eur. J. Biochem. 268 (23): 6076-82. doi:10.1046/j. ... Meikrantz W, Schlegel R (1996). "Suppression of apoptosis by dominant negative mutants of cyclin-dependent protein kinases". J ... Ren S, Rollins BJ (2004). "Cyclin C/cdk3 promotes Rb-dependent G0 exit". Cell. 117 (2): 239-51. doi:10.1016/S0092-8674(04)00300 ...
"Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proceedings of the National ... The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate ... "Entrez Gene: CDK8 cyclin-dependent kinase 8". Nemet J, Jelicic B, Rubelj I, Sopta M (Feb 2014). "The two faces of Cdk8, a ... Cyclin-dependent kinase 8 has been shown to interact with: CCNC, CREB binding protein, CRSP3, MED1, MED12, MED14, MED16, MED17 ...
Two key classes of regulatory molecules, cyclins and cyclin-dependent kinases (CDKs), determine a cell's progress through the ... cyclin A, DNA polymerase, thymidine kinase, etc. Cyclin E thus produced binds to CDK2, forming the cyclin E-CDK2 complex, which ... Nigg EA (June 1995). "Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle". BioEssays. 17 (6): 471-80 ... Cyclin D is the first cyclin produced in the cell cycle, in response to extracellular signals (e.g. growth factors). Cyclin D ...
SLBP are marked for degradation by phosphorylation at two threonine residues by cyclin dependent kinases, possibly cyclin A/ ... "NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription". Genes & Development. 14 (18): ... The mitotic kinase aurora B phosphorylates histone H3 at serine 10, triggering a cascade of changes that mediate mitotic ... NPAT activates histone gene expression only after it has been phosphorylated by the G1/S-Cdk cyclin E-Cdk2 in early S phase.[ ...
The cell cycle is regulated by a series of signalling factors and complexes such as cyclin-dependent kinases and p53, to name a ... 6] Viruses range from 0.005 to .03 microns in size whereas Bacteria range from 1-5 microns.[7] Modern day cell biology research ...
... , 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. • ...
Li Y, Jenkins CW, Nichols MA, Xiong Y. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. „ ... The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. „Cell". 75 (4), s. 805-816, 1993. ... a b Entrez Gene: CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1). ... Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell ...
Cell cycle progression is controlled by ordered action of cyclin-dependent kinases (CDKs), activated by specific cyclins that ... is one of the 19S subcomponents that also tightly binds the cyclin-dependent kinase CDK4 and plays a key role in recognizing ... In particular, exit from mitosis requires the proteasome-dependent dissociation of the regulatory component cyclin B from the ... the ATP-dependent proteolytic complex that was responsible for ubiquitin-dependent protein degradation was discovered and was ...
CDK4, CMM3, PSK-J3, cyclin-dependent kinase 4, cyclin dependent kinase 4. ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. Sci. U.S. ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ...
"Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational ... 347 (6289): 203-6. doi:10.1038/347203a0. PMID 2203971.. *^ Cusack S (December 1997). "Aminoacyl-tRNA synthetases". Current ...
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 ... Linalol (3,7-dimetylooktadi-1,6-en-3-ol) - organiczny związek chemiczny, nienasycony alkohol alifatyczny, należący do grupy ... InChI=1S/C10H18O/c1-5-10(4,11)8-6-7-9(2)3/h5,7,11H,1,6,8H2,2-4H3 ...
All these phases in the cell cycle are highly regulated by cyclins, cyclin-dependent kinases, and other cell cycle proteins. ... Generation of pressure is dependent on formin-mediated F-actin nucleation[71] and Rho kinase (ROCK)-mediated myosin II ... This can occur when cells become overcrowded (density-dependent inhibition) or when they differentiate to carry out specific ... Ramanathan SP, Helenius J, Stewart MP, Cattin CJ, Hyman AA, Muller DJ (February 2015). "Cdk1-dependent mitotic enrichment of ...
... endothelin receptor A and cyclin dependent kinase inhibitor. Mutations in interleukin 6 may be protective.[citation needed]. ... The inflammatory mediators are: Interleukin 1 beta, Interleukin 6, Tumor necrosis factor alpha (TNF alpha), MMP1, MMP2, MMP9, ... A ruptured microaneurysm may cause an intracerebral hemorrhage, presenting as a focal neurological deficit.[6] ... 6] Symptoms of a subarachnoid hemorrhage differ depending on the site and size of the aneurysm.[6] Symptoms of a ruptured ...
cyclin-dependent protein serine/threonine kinase inhibitor activity. • protein binding. • cyclin-dependent protein kinase ... cyclin-dependent protein kinase holoenzyme complex. • nucleus. • nucleoplasm. • cytosol. • intracellular membrane-bounded ... Cyclin-dependent kinase inhibitor 1A (p21, Cip1). Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human ... regulation of cyclin-dependent protein serine/threonine kinase activity. • G1/S transition of mitotic cell cycle. • G2/M ...
... phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase" ... "Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV transcription by a Tat-dependent mechanism". J. Immunol. 169 ... A dose-dependent response was not observed, raising questions about the robustness of the findings.[21] ... of cellular CDK9 and cyclin T1, and hence increases the production of full-length viral RNA.[8] ...
"CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle progression". Cell. 151 (6): 1308-18. doi: ... "The turn motif is a phosphorylation switch that regulates the binding of Hsp70 to protein kinase C". The Journal of Biological ... When Hsp70 proteins are ADP bound, the lid is closed, and peptides are tightly bound to the substrate binding domain.[6] ...
Jiang MC, Liao CF, Tai CC (June 2002). "CAS/CSE 1 stimulates E-cadhrin-dependent cell polarity in HT-29 human colon epithelial ... "Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes". The Journal of Cell Biology. 128 (5): ... Laoukili J, Alvarez-Fernandez M, Stahl M, Medema RH (September 2008). "FoxM1 is degraded at mitotic exit in a Cdh1-dependent ... The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein composed of five extracellular cadherin repeats, a ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... 1omw: Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and ... Buhl AM, Osawa S, Johnson GL (1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human ... 2bcj: Crystal Structure of G Protein-Coupled Receptor Kinase 2 in Complex with Galpha-q and Gbetagamma Subunits ...
Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bad (a Bcl-2 ... Caspases are proteins that are highly conserved, cysteine-dependent aspartate-specific proteases. There are two types of ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... the protein is cleaved by a calcium-dependent calpain protease ... "Apoptosis induced by Oropouche virus infection in HeLa cells is dependent on virus protein expression". Virus Research. 149 (1 ...
A prominent kinase is cyclin-dependent kinase (or CDK), which comprises a sub-family of protein kinases. As their name implies ... "Biochemical characterization of the human cyclin-dependent protein kinase activating kinase. Identification of p35 as a novel ... CDKs are heavily dependent on specific cyclin molecules for activation. Once combined, the CDK-cyclin complex is capable of ... Herbst EA, MacPherson RE, LeBlanc PJ, Roy BD, Jeoung NH, Harris RA, Peters SJ (Jan 2014). "Pyruvate dehydrogenase kinase-4 ...
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 ... La mayoría de las células inmunes (o leucocitos) secretan TGFB1.[6]​ TGF-β1 y células TEditar. Algunos tipos de células T, como ...
... 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". ... 31 (6): 961-7. doi:10.1093/carcin/bgq069. PMID 20400477.. *^ a b c d e f g Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J ...
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 ... Int Rev Immunol. 6,163-75 PMID 2152500. *Learmont JC, Geczy AF, Mills J, Ashton LJ, Raynes-Greenow CH, Garsia RJ, Dyer WB, ... 6] Pada awal tahun 1984, Robert Gallo dari Amerika Serikat juga meneliti tentang virus penyebab AIDS yang disebut HTLV-III.[5][ ... 6] Bersama dengan Luc Montagnier, mereka membuktikan bahwa virus tersebut merupakan penyebab AIDS.[ ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... Gαs activates the cAMP-dependent pathway by stimulating the production of cyclic AMP (cAMP) from ATP. This is accomplished by ... The cAMP-dependent pathway is used as a signal transduction pathway for many hormones including:. *ADH - Promotes water ... cAMP can then act as a second messenger that goes on to interact with and activate protein kinase A (PKA). PKA can ...
These transitions are controlled by the cyclin-dependent kinase Cdk1.[6] Though the proteins that control Cdk1 are well ... a cyclin-dependent kinase, on a tyrosine residue. Cdc2 drives entry into mitosis by phosphorylating a wide range of targets. ... The protein kinase Cdr2 (which negatively regulates Wee1) and the Cdr2-related kinase Cdr1 (which directly phosphorylates and ... Wu L, Russell P (June 1993). "Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase". Nature. 363 (6431): 738-41. ...
The process follows fertilization, with the transfer being triggered by the activation of a cyclin-dependent kinase complex.[1] ... high levels of proteins that control cell cycle progression such as the cyclins and their associated cyclin-dependent kinases ( ... cdk). The complex Cyclin B/CDK1 a.k.a. MPF (maturation promoting factor) promotes entry into mitosis. ... 6] This group includes annelids, molluscs, and sipuncula. Spiral cleavage can vary between species, but generally the first two ...
CDK抑制因子(英语:Cyclin-dependent kinase inhibitor protein). *INK4a/ARF(p14arf/p16、p15、p18、p19) ... Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle. BioEssays. June 1995, 17 (6): 471-80. PMID ... 細胞週期的進行是由不同的週期素(Cyclin)所調控。週期素意味著這些蛋白質的表現量會隨著細胞週期的進行而有所變化,進而確認週期素原來是扮演細胞
Liu H, Di Cunto F, Imarisio S, Reid LM (Jan 2003). "Citron kinase is a cell cycle-dependent, nuclear protein required for G2/M ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... protein kinase activity. • PDZ domain binding. • SH3 domain binding. • scaffold protein binding. • metal ion binding. • kinase ...
Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle ... Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR017441, Protein_kinase_ATP_BS. IPR008271, Ser/Thr_kinase_AS. ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR017441, Protein_kinase_ATP_BS. IPR008271, Ser/Thr_kinase_AS. ...
cyclin-dependent kinase 6Imported. Automatic assertion inferred from database entriesi ... tr,A0A384BPK8,A0A384BPK8_URSMA cyclin-dependent kinase 6 OS=Ursus maritimus OX=29073 GN=CDK6 PE=4 SV=1 ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR008271, Ser/Thr_kinase_AS. ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR008271, Ser/Thr_kinase_AS. ...
It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18. ... Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE ... Protein Kinases: 9706*Protein-Serine-Threonine Kinases: 1353*Cyclin-Dependent Kinases: 639*Cyclin-Dependent Kinase 6: 44*human ... Proline-Directed Protein Kinases: 26*Cyclin-Dependent Kinases: 639*Cyclin-Dependent Kinase 6: 44*human CDK6 protein ...
Cyclin-dependent kinase 6 (CDK6) binds to and is activated by cyclin D1 and thereby enhances the transition of cells through ... Cyclin-dependent kinase 6 associates with the androgen receptor and enhances its transcriptional activity in prostate cancer ... Cyclin-dependent kinase 6 associates with the androgen receptor and enhances its transcriptional activity in prostate cancer ... Cyclin-dependent kinase 6 associates with the androgen receptor and enhances its transcriptional activity in prostate cancer ...
Crystal Structure of a Human Cyclin-Dependent Kinase 6 Complex with a Flavonol Inhibitor, Fisetin.. Lu, H.S., Chang, D.J., ... Cyclin-dependent kinases (CDKs) play a central role in cell cycle control, apoptosis, transcription, and neuronal functions. ... Cyclin-dependent kinases (CDKs) play a central role in cell cycle control, apoptosis, transcription, and neuronal functions. ... Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin. *DOI: 10.2210/pdb1XO2/pdb ...
A Requirement for Cyclin-Dependent Kinase 6 in Thymocyte Development and Tumorigenesis. Miaofen G. Hu, Amit Deshpande, Miriam ... A Requirement for Cyclin-Dependent Kinase 6 in Thymocyte Development and Tumorigenesis ... A Requirement for Cyclin-Dependent Kinase 6 in Thymocyte Development and Tumorigenesis ... A Requirement for Cyclin-Dependent Kinase 6 in Thymocyte Development and Tumorigenesis ...
Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors. J ... A Requirement for Cyclin-Dependent Kinase 6 in Thymocyte Development and Tumorigenesis. Miaofen G. Hu, Amit Deshpande, Miriam ... Cyclin-dependent kinase 6 (CDK6), a cyclin D-responsive regulator of the retinoblastoma protein (pRB) pathway, seems to be of ... Expression of cyclin-dependent kinase 6 (cdk6) and frequent loss of CD44 in nasal-nasopharyngeal NK/T-cell lymphomas: ...
Cyclin-Dependent Kinase Inhibitor p21. *Cyclin-Dependent Kinase Inhibitor p27. *Cyclin-Dependent Kinases/antagonists & ... a cyclin-dependent kinase inhibitor, and neuron-like morphology in LNCaP prostate tumor cells.. Mori S1, Murakami-Mori K, ... Western blot analysis showed that the protein levels of cyclin-dependent kinase-2 (CDK2), CDK4, and CDK6 were decreased, while ... In vitro kinase assays revealed that the CDK-associated histone H1 and CDK4- and CDK6-associated pRb kinase activities were ...
CYCLIN-DEPENDENT KINASE 2 (CDK2) COMPLEXED WITH N-METHYL-{4-[2-(7-OXO-6,7-DIHYDRO-8H-[1,3]THIAZOLO[5,4-E]INDOL-8-YLIDENE) ... Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray ... were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepared as a homologue of the 3 ... were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepa ... ...
One such target is cyclin-dependent kinase 6 (CDK6), a serine/threonine kina … ... One such target is cyclin-dependent kinase 6 (CDK6), a serine/threonine kinase that plays a vital role in cell cycle ... Inhibition of cyclin-dependent kinase 6 suppresses cell proliferation and enhances radiation sensitivity in medulloblastoma ... or by inhibiting kinase function with a small molecule inhibitor, PD0332991. Cell proliferation was assessed by colony focus ...
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 ...
IL-6). This response is lost in cell lines derived from advanced lesions, a phenomenon which may contribute to tumor ... cell lines derived from early stage primary tumors are particularly sensitive to growth arrest induced by interleukin-6 ( ... which could not be explained by changes in levels of G1 cyclins (D1, E), cdks (cdk4, cdk2) or by loss of cyclin/cdk complex ... In contrast, IL-6 failed to induce p21WAF1/CIP1 transcript and did not increase p21WAF1/CIP1 or p27kip1 proteins in any of the ...
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 ...
Correction to "Fisetin, an Inhibitor of Cyclin-Dependent Kinase 6, Down-Regulates Nuclear Factor-κB-Regulated Cell ... Correction to "Fisetin, an Inhibitor of Cyclin-Dependent Kinase 6, Down-Regulates Nuclear Factor-κB-Regulated Cell ... Correction to "Fisetin, an Inhibitor of Cyclin-Dependent Kinase 6, Down-Regulates Nuclear Factor-κB-Regulated Cell ... Correction to "Fisetin, an Inhibitor of Cyclin-Dependent Kinase 6, Down-Regulates Nuclear Factor-κB-Regulated Cell ...
Cyclin Dependent Kinase 6 (Cell Division Protein Kinase 6 or... ... Cell Division Protein Kinase 6 or Serine/Threonine Protein ... Kinase PLSTIRE or CDK6 or EC 2.7.11.22) - Pipeline Review, H2 2017 report by Global Markets Direct. ... 103 Pages Report] Check for Discount on Cyclin Dependent Kinase 6 ( ... Cyclin Dependent Kinase 6 (Cell Division Protein Kinase 6 or Serine/Threonine Protein Kinase PLSTIRE or CDK6 or EC 2.7.11.22) ...
We have found that the putative miR-107 target cyclin-dependent-kinase 6 (CDK6) expression is increased by TLR4 as a result of ... Toll-like receptor 4 (TLR4) down-regulates microRNA-107 increasing macrophage adhesion via cyclin-dependent kinase 6. ... Toll-like receptor-4 (TLR4) down-regulates microRNA-107 increasing macrophage adhesion via cyclin-dependent kinase 6.pdf ( ... down-regulates microRNA-107 increasing macrophage adhesion via cyclin-dependent kinase 6, Journal of Biological Chemistry, 286 ...
Cyclin-dependent kinases (CDKs) play a central role in cell cycle control, apoptosis, transcription and neuronal functions. ... We describe here the crystal structure of human CDK6 in complex with a viral cyclin and a flavonol inhibitor, fisetin. Fisetin ... This complex structure is the first description of an inhibitor complex with a kinase from the CDK4/6 subfamily and can provide ... However, CDK2 and HCK kinase in complex with other flavone inhibitors such as quercetine and flavopiridol showed a different ...
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 ... and its value in predicting response to CDK4/6 inhibitors warrants further investigation. ClinicalTrials.gov, NCT01723774. ... biomarker for CDK4/6 inhibitors. We examined the drug-induced change in serum TK1 as well as its correlation with change in ...
Cyclin-dependent kinase synonyms, Cyclin-dependent kinase pronunciation, Cyclin-dependent kinase translation, English ... dictionary definition of Cyclin-dependent kinase. n. Any of various enzymes that catalyze the transfer of a phosphate group ... Cyclin-dependent kinase - definition of Cyclin-dependent kinase by The Free Dictionary https://www.thefreedictionary.com/Cyclin ... kinase. (redirected from Cyclin-dependent kinase). Also found in: Thesaurus, Medical, Acronyms, Encyclopedia, Wikipedia. ki· ...
CDK11B cyclin dependent kinase 11B [Homo sapiens] CDK11B cyclin dependent kinase 11B [Homo sapiens]. Gene ID:984 ... cyclin-dependent kinase 11B. Names. CDC-related protein kinase p58. PITSLRE serine/threonine-protein kinase CDC2L1. cell ... Title: Preclinical evaluation of cyclin dependent kinase 11 and casein kinase 2 survival kinases as RNA interference targets ... cyclin dependent kinase 11Bprovided by HGNC. Primary source. HGNC:HGNC:1729 See related. Ensembl:ENSG00000248333 MIM:176873 ...
We therefore investigated the therapeutic potential of specific cyclin-dependent kinase (CDK) inhibition in MYC-driven breast ... MYC-dependent and MYC-independent cell lines were classified based on their sensitivity to siRNA-mediated MYC knockdown. We ... An alternative approach is to identify genes that are synthetically lethal in MYC-dependent cancer. Recent studies have ... Overall, these results suggest that further investigation of CDK1 inhibition as a potential therapy for MYC-dependent breast ...
Cyclin-dependent kinases are a type of serine/threonine kinase which are activated by cyclins to drive the progress of the cell ... Cyclin-dependent kinases are a type of serine/threonine kinase which are activated by cyclins to drive the progress of the cell ... Cyclin Dependent Kinases in the Cell Cycle. Initially, a mitogenic stimulus leads to the upregulation of cyclin D gene ... Control of Cyclin Dependent Kinases. Upon external signals, CDK inhibitors can be used to block the CDK kinase activity, ...
Table 2: Cyclin-Dependent Kinase 9 (CDK9) Inhibitor Therapeutic Products in Clinical Stages. Table 3: Cyclin-Dependent Kinase 9 ... Figure 2: Cyclin-Dependent Kinase 9 (CDK9) Inhibitor Therapeutic Products in Clinical Stages. Figure 3: Cyclin-Dependent Kinase ... 2. Cyclin-Dependent Kinase 9 (CDK9) Inhibitor - Overview. 3. Pipeline Therapeutics*An Overview of Pipeline Products for Cyclin- ... Dependent Kinase 9 (CDK9) Inhibitor 4. Comparative Analysis. 5. Cyclin-Dependent Kinase 9 (CDK9) Inhibitor Pipeline Products in ...
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 ...
1996) Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27Kip1. Cell 85:721-732. ... Two families of cyclin-dependent kinase (CDK) inhibitors, totaling seven genes, have been identified in mammalian cells. Their ... 1999) The p21Cip1 and p27Kip1 CDK inhibitors are essential activators of cyclin D-dependent kinases in murine fibroblasts. ... 1994) Deletion of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 368:753-756. ...
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. CDK4 and CDK6 are enzymes important in cell division. CDK4/6 inhibitors ... PI3 kinase inhibitors. PI3 kinase is an enzyme important in cell growth. The PIK3CA gene helps control PI3 kinase enzyme ... PI3 kinase inhibitors are a class of drugs designed to interrupt PI3 kinase signals and stop the growth of cancer cells. ... Tyrosine-kinase inhibitors. Tyrosine-kinase inhibitors are a class of drugs that target enzymes important for cell functions ( ...
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 ... A woman with child bearing potential is defined as not surgically sterile or being post-menopausal for less than 6 months. ... Patients with platinum-sensitive or platinum-resistant disease defined by recurrence or progression of disease , 6 months or ≤ ...
Cyclin-dependent kinase 6. CDKN:. Cyclin-dependent kinase inhibitor. c-Kit:. v-kit Hardy-Zuckerman 4 feline sarcoma viral ... phosphatidylinositol-3-kinase regulatory subunit beta, PI3K. ) mRNA and modulates its expression. PI3K. is a regulatory subunit ... H. Sakai, A. Sato, Y. Aihara et al., "MKK7 mediates miR-493-dependent suppression of liver metastasis of colon cancer cells," ... 16], both of them were able to directly modulate the expression of DAPK1 (death-associated protein kinase 1) and KLF4 (Krüppel- ...
... cyclin-dependent kinase 6 (CDK6), calmodulin 1 (CALM1), transcription factor binding to IGHM enhancer 3 (TFE3), EWS RNA-binding ... calcium/calmodulin-dependent protein kinase 1 (Camk1), and glutamate-ammonia ligase (Glul) [68], and both Bach1 and Bach2 ... H. Suzuki, S. Tashiro, S. Hira et al., "Heme regulates gene expression by triggering Crm1‐dependent nuclear export of Bach1," ... D. Meng, X. Wang, Q. Chang et al., "Arsenic promotes angiogenesis in vitro via a heme oxygenase-1-dependent mechanism," ...
  • Cyclin-dependent kinase 6 (CDK6) binds to and is activated by cyclin D1 and thereby enhances the transition of cells through the G 1 phase of the cell cycle. (pnas.org)
  • This effect of CDK6 does not require its kinase activity and is inhibited by cyclin D1 and p16 INK4a . (pnas.org)
  • We also show that this effect is independent of cyclin D1 and CDK6 kinase activity. (pnas.org)
  • We describe here the crystal structure of human CDK6 in complex with a viral cyclin and a flavonol inhibitor, fisetin. (rcsb.org)
  • Fisetin binds to the active form of CDK6, forming hydrogen bonds with the side chains of residues in the binding pocket that undergo large conformational changes during CDK activation by cyclin binding. (rcsb.org)
  • Cyclin-dependent kinase 6 (CDK6) promotes cell cycle progression and is overexpressed in human lymphoid malignancies. (aacrjournals.org)
  • Using the OP9-DL1 system to deliver temporally controlled Notch receptor-dependent signaling, we show that CDK6 is required for Notch-dependent survival, proliferation, and differentiation. (aacrjournals.org)
  • These results show a critical requirement for CDK6 in Notch/Akt-dependent T-cell development and tumorigenesis and strongly support CDK6 as a specific therapeutic target in human lymphoid malignancies. (aacrjournals.org)
  • Cyclin-dependent kinase 6 (CDK6), a cyclin D-responsive regulator of the retinoblastoma protein (pRB) pathway, seems to be of central importance in T-cell development. (aacrjournals.org)
  • The activity of CDK6 is very tightly controlled by association with D-cyclins ( 7 ) and two families of CDK inhibitors, including the CIP/KIP family and the inhibitors of CDK4 (INK4) family proteins ( 9 ). (aacrjournals.org)
  • In contrast, cyclin D2 expression is high in the DN1-DN3 stages before pre-TCR assembly and barely detectable after pre-TCR assembly ( 10 ), suggesting that CDK6 may use different cyclin partners in the thymocyte developmental stages. (aacrjournals.org)
  • Consistent with a key role for CDK6 as a D-cyclin partner in thymocytes, knockout (KO) of CDK4 or CDK2 was shown to have no significant effect on T-cell development ( 11 , 12 ), but significantly decreased thymic cellularity was observed in a CDK6 KO animal ( 13 ). (aacrjournals.org)
  • Following IL-6 treatment of LNCaP, Western blot analysis showed that the protein levels of cyclin-dependent kinase-2 (CDK2), CDK4, and CDK6 were decreased, while accumulation of CDK inhibitor p27(Kip1) was rapidly and markedly induced. (nih.gov)
  • In vitro kinase assays revealed that the CDK-associated histone H1 and CDK4- and CDK6-associated pRb kinase activities were significantly inhibited in IL-6-treated LNCaP. (nih.gov)
  • One such target is cyclin-dependent kinase 6 (CDK6), a serine/threonine kinase that plays a vital role in cell cycle progression and differentiation. (nih.gov)
  • To investigate the role of CDK6 in medulloblastoma, we assayed the effect of CDK6 inhibition on proliferation by depleting expression with RNA interference (RNAi) or by inhibiting kinase function with a small molecule inhibitor, PD0332991. (nih.gov)
  • 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)
  • The latest report Cyclin Dependent Kinase 6 - Pipeline Review, H2 2017, outlays comprehensive information on the Cyclin Dependent Kinase 6 (Cell Division Protein Kinase 6 or Serine/Threonine Protein Kinase PLSTIRE or CDK6 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 6 (Cell Division Protein Kinase 6 or Serine/Threonine Protein Kinase PLSTIRE or CDK6 or EC 2.7.11.22) targeted therapeutics development with respective active and dormant or discontinued projects. (reportsnreports.com)
  • 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 6 (CDK6) bound to the inhibitor ribociclib (detail view). (news-medical.net)
  • Levels of cyclin-dependent kinase 1 (CDK1) and CDK6, Bcl2 and BAX and cytochrome c were quantified by specific ELISA. (who.int)
  • 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)
  • These characteristics of DPSCs are mainly due to the fact that they exhibit elevated amounts of cell cycling molecules, one being cyclin-dependent kinase 6 (CDK6), present in the dental pulp tissue. (wikipedia.org)
  • RT "Identification of G1 kinase activity for cdk6, a novel cyclin D RT partner. (genome.jp)
  • RT "Transforming activity of Fbxo7 is mediated specifically through RT regulation of cyclin D/cdk6. (genome.jp)
  • RT "Preferences for phosphorylation sites in the retinoblastoma protein RT of D-type cyclin-dependent kinases, Cdk4 and Cdk6, in vitro. (genome.jp)
  • The present study indicated that cyclin‑dependent kinase 6 (CDK6) was the direct target gene of miR‑25 using mRNA and protein expression analysis, and luciferase assays. (spandidos-publications.com)
  • In the current study, it was hypothesized that the expression of miR-25 was inhibited in TNF-α-stimulated VSMCs and that overexpression of miR-25 in the VSMCs inhibited cell proliferation by targeting cyclin-dependent kinase 6 (CDK6). (spandidos-publications.com)
  • This gene encodes a cyclin-dependent kinase inhibitor, which forms a complex with CDK4 or CDK6, and prevents the activation of the CDK kinases, thus the encoded protein functions as a cell growth regulator that controls cell cycle G1 progression. (genecards.org)
  • The transition through G1 to S phase is regulated by cyclins, cyclin-dependent kinases (CDK)-CDK4 and CDK6 and their inhibitors. (thefreedictionary.com)
  • Some CDKs, such as CDK1-CDK4, CDK6 and perhaps CDK11, are involved in progression through the cell cycle, whereas CDK7 has dual roles as a CDK-activating kinase (CAK) and a regulator of the transcriptional machinery. (thefreedictionary.com)
  • Indianapolis, Indiana-based global pharmaceuticals specialist Eli Lilly and Company's (NYSE: LLY) Phase 3 JUNIPER study evaluating Verzenio (abemaciclib), a cyclin-dependent kinase 4 and CDK6 inhibitor, as monotherapy in KRAS-mutated, advanced non-small lung cancer (NSCLC) did not meet its primary endpoint of overall survival (OS), the company said. (thefreedictionary.com)
  • The two cell-cycle kinases CDK4 and CDK6 normally facilitate cell-cycle progression but are abnormally activated in certain cancers. (thefreedictionary.com)
  • The 4-keto group and the 3-hydroxyl group of fisetin are hydrogen bonded with the backbone in the hinge region between the N-terminal and C-terminal kinase domain, as has been observed for many CDK inhibitors. (rcsb.org)
  • However, CDK2 and HCK kinase in complex with other flavone inhibitors such as quercetin and flavopiridol showed a different binding mode with the inhibitor rotated by about 180 degrees. (rcsb.org)
  • and expression, degradation, and availability of naturally occurring protein inhibitors and subcellular localization of these various regulatory components ( 2 , 5 , 6 ). (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)
  • Western blotting was used to measure cyclin-dependent kinase (CDK) inhibitors p21 and p27 that arrest cell cycle. (thefreedictionary.com)
  • p27(KIP1) is a member of the CIP1/KIP1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. (thefreedictionary.com)
  • Some of the non-biological drugs, known as Cyclin-dependent kinase (CDK) inhibitors, are currently being tested for use in cancer treatment. (thefreedictionary.com)
  • Altered prostatic epithelial proliferation and apoptosis, prostatic development and serum testosterone in mice lacking cyclin-dependent kinase inhibitors," Biology of Reproduction 73(5): 951-958. (thefreedictionary.com)
  • We then inhibited CDKs including CDK4/6, CDK2 and CDK1 individually using either RNAi or small molecule inhibitors, and compared sensitivity to CDK inhibition with MYC dependence in breast cancer cells. (biomedcentral.com)
  • Upon external signals, CDK inhibitors can be used to block the CDK kinase activity, thereby preventing the cell cycle from being driven forward. (news-medical.net)
  • 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)
  • PI3 kinase inhibitors are a class of drugs designed to interrupt PI3 kinase signals and stop the growth of cancer cells. (komen.org)
  • CDK4/6 inhibitors are a class of drugs designed to interrupt the growth of cancer cells. (komen.org)
  • Abemaciclib (Verzenio) , palbociclib (Ibrance) and ribociclib (Kisqali) are CDK4/6 inhibitors FDA-approved for metastatic breast cancer treatment. (komen.org)
  • ViroStatics has discovered and is developing novel, highly potent inhibitors, which selectively target CDK4/6/9 in a single molecule for a multifaceted approach for the durable treatment of cancers and viral diseases. (wikipedia.org)
  • The Kinase Enzyme Systems allow you to easily screen and profile kinase inhibitors. (promega.com)
  • In addition, tamoxifen, which is commonly used in premenopausal patients, has not been tested in combination with any of the CDK4/6 inhibitors like Kisqali or Ibrance. (breastcancer.org)
  • Indeed, the only nuclear G1/S molecules are the cell cycle inhibitors, pRb, p57, and variably, p21: none of the cyclins or cdks necessary to drive human β-cell proliferation are present in the nuclear compartment. (diabetesjournals.org)
  • 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)
  • For comparison, in quiescent cells, all four of the inhibitors of cell cycle progression tested (anti-Ras, anti-cyclin D1, serum removal, and cycloheximide) became ineffective at essentially the same point in G 1 phase, approximately 4 h prior to the beginning of DNA synthesis. (asm.org)
  • Cyclin-dependent kinase (CDK) 4/6 inhibitors have become standard of care in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer. (medworm.com)
  • The aim of this article is to give a short overview of the existing efficacy data, to summarize the recommended clinical monitoring procedures for patients under CDK4/6 inhibitors, and to shed light on the clinical management of the most common treatment-emergent adverse even. (medworm.com)
  • Cyclin-dependent kinases (CDKs) play a central role in cell cycle control, apoptosis, transcription, and neuronal functions. (rcsb.org)
  • Our results show that IL-6 treatment of early stage melanoma cell lines caused G1 arrest, which could not be explained by changes in levels of G1 cyclins (D1, E), cdks (cdk4, cdk2) or by loss of cyclin/cdk complex formation. (nih.gov)
  • These cyclins oscillate, increasing and decreasing at different stages, binding to CDKs and driving the cell cycle forward. (news-medical.net)
  • In addition to cyclin levels, this provides and additional way to control the activity of CDKs. (news-medical.net)
  • Cyclin-dependent kinases (CDKs) and Cyclin D have been known to increase in aggressive thyroid cancer. (yonsei.ac.kr)
  • To this end, ViroStatics has focused on selectively targeting the Cyclin Dependent Kinases (CDKs) involved in these perturbations (CDK9 and CDK4/6). (wikipedia.org)
  • Cyclin-dependent kinases (cdks) are critical regulators of cell cycle progression and RNA transcription. (dana-farber.org)
  • 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)
  • The results indicate that inhibition of Cdk4/6 alone is sufficient to cause tumor regression and a net reduction in tumor burden in some tumors. (aacrjournals.org)
  • 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)
  • Therapeutically active doses of PD 0332991 in vivo cause down-regulation of proteins and genes in tumor tissue that are consistent with inhibition of Cdk4/6. (aacrjournals.org)
  • We sought to determine whether resistance to growth inhibition by IL-6 can be explained by oncogenic alterations in cell cycle regulators or relevant components of intracellular signaling. (nih.gov)
  • Thus, our results suggest that in early stage human melanoma cells, IL-6 induced growth inhibition involves induction of p21WAF1/CIP1 which is lost in the course of tumor progression presumably as a result of a dominant oncogenic event. (nih.gov)
  • Cyclin-Dependent Kinase 11 (CDK11) Is Required for Ovarian Cancer Cell Growth In Vitro and In Vivo, and Its Inhibition Causes Apoptosis and Sensitizes Cells to Paclitaxel. (nih.gov)
  • We therefore investigated the therapeutic potential of specific cyclin-dependent kinase (CDK) inhibition in MYC-driven breast cancer. (biomedcentral.com)
  • Overall, these results suggest that further investigation of CDK1 inhibition as a potential therapy for MYC-dependent breast cancer is warranted. (biomedcentral.com)
  • Retinoblastoma protein (Rb) usually functions to inhibit the transcription factor E2F, however, when cyclin-D-CDK4 phosphorylates the Rb protein, this relinquishes inhibition of E2F and leads to the production of genes required for entering the S phase. (news-medical.net)
  • Vol 7: PD-0332991 induces G1 arrest of colorectal carcinoma cells through inhibition of the cyclin-dependent kinase-6 and retinoblastoma protein axis. (duhnnae.com)
  • 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)
  • This work represents a first step toward defining tumors that are more likely to respond to Aurora kinase inhibition. (dana-farber.org)
  • Inhibits cell cycle progression via inhibition of CDK4 kinase. (springer.com)
  • Pharmacologic inhibition of cyclin-dependent kinases 4 and 6 arrests the growth of glioblastoma multiforme intracranial xenografts. (ucsf.edu)
  • Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). (rcsb.org)
  • Cell cycle arrest induced by MYC knockdown was accompanied by a decrease in CDK2 activity, but inactivation of CDK2 did not selectively affect the viability of MYC-dependent breast cancer cells. (biomedcentral.com)
  • Cyclin A is also produced, which binds to CDK2 and stimulates DNA replication. (news-medical.net)
  • A dominant-negative Cdc2 mutant arrested cells at the G2 to M phase transition, whereas mutants of the cyclin-dependent kinases Cdk2 and Cdk3 caused a G1 block. (sciencemag.org)
  • The miR-107 sequence occurs in an intron within the sequence encoding the gene for Pantothenate kinase-1? (tcd.ie)
  • This gene encodes a member of the serine/threonine protein kinase family. (nih.gov)
  • The protein kinase encoded by this gene can be cleaved by caspases and may play a role in cell apoptosis. (nih.gov)
  • The differences at each stage are due to a balance between the gene expression of each cyclin and the ubiquitin-proteasome system which breaks them down. (news-medical.net)
  • Initially, a mitogenic stimulus leads to the upregulation of cyclin D gene expression, which binds to CDK4. (news-medical.net)
  • 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)
  • 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)
  • 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)
  • Gene that encodes cyclin A1. (springer.com)
  • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) is a Protein Coding gene. (genecards.org)
  • GO annotations related to this gene include protein kinase binding and cyclin-dependent protein serine/threonine kinase inhibitor activity . (genecards.org)
  • The discovery of mutations in the α-synuclein gene, which encodes the main protein misfolded in PD aggregates, together with mutations in genes encoding ubiquitin regulatory molecules, including PTEN-induced kinase 1 (PINK1), Parkin, and FBX07, has provided an opportunity to dissect out the molecular basis of ubiquitin signalling disruption in PD, and this knowledge will be critical for developing novel therapeutic strategies in PD that target the ubiquitin system. (biochemj.org)
  • They analyzed DNA from eight families with ALS and 30 families with FTLD-U and found a missense mutation in exon 6 of the TDP-43 gene, where a threonine appeared instead of an alanine in amino acid position 315. (alzforum.org)
  • The second study, out today in Science, by scientists at King's College London, the University of Sydney, and the Northcott Neuroscience Laboratory at the ANZAC Research Institute in Australia, also found missense mutations within exon 6 of the TDP-43 gene. (alzforum.org)
  • Led by Christopher Shaw at King's College, the British-Australian researchers sequenced all six exons of the TDP-43 gene in 500 controls and 200 sporadic ALS cases (all of British descent) and found in one a missense mutation in exon 6, substituting lysine for glutamine (Q331K). (alzforum.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)
  • It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (wikipedia.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)
  • Key target genes in this process include master regulators of the cell cycle, such as cyclin E, which regulates G(1) progression, and cyclin A, which is required for the initiation of DNA synthesis. (semanticscholar.org)
  • Serine/threonine kinases that promote cell cycle progression. (springer.com)
  • Dominant-negative mutations were used to address the requirement for kinases of this family in progression through the human cell cycle. (sciencemag.org)
  • Cyclin D2, a positive regulator of G1 progression, shows a unique localization within radial glial (RG) cells (i.e., the neural progenitor in the developing neocortex). (wiley.com)
  • Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. (curehunter.com)
  • This article is from Oncology Letters, volume 7.AbstractPreclinical and clinical studies have demonstrated the anticancer activity of PD-0332991, a selective cyclin-dependent kinase 4-6 CDK4-6 inhibitor, in the treatment of various types of cancer in a retinoblastoma protein RB-dependent manner. (duhnnae.com)
  • For example, passage through G 1 phase in quiescent and proliferating cells exhibits several important molecular differences, including expression of the cyclin-inhibitory protein p27 kip1 ( 3 ), Cdc6 ( 42 ), and Fos and related proteins ( 14 ), and formation of a complex between E2F and the retinoblastoma protein (Rb)-related p130 ( 19 , 34 ). (asm.org)
  • An alternative approach is to identify genes that are synthetically lethal in MYC-dependent cancer. (biomedcentral.com)
  • Recent studies have identified several cell cycle kinases as MYC synthetic-lethal genes. (biomedcentral.com)
  • Consequently, an alternative approach which has recently received great attention is to identify genes that are synthetically lethal in MYC-dependent cancers. (biomedcentral.com)
  • These genes include cyclin E, which binds to CDK4, driving the cell cycle into the S phase. (news-medical.net)
  • 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)
  • 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)
  • 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)
  • This mutation can affect PI3 kinase and cause the tumor to grow. (komen.org)
  • In this context, miRNAs can play a functionality of either tumor suppressors or oncogenes (oncomirs) [ 6 ]. (hindawi.com)
  • The cyclin D/Rb/E2F1 pathway was investigated in vitro using MCL cell lines and primary tumor cells. (aacrjournals.org)
  • This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the antiproliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. (elsevier.com)
  • Ibrance capsules for oral administration contain 125 mg, 100 mg, or 75 mg of palbociclib, a kinase inhibitor. (rxlist.com)
  • PFE ) drug palbociclib (Ibrance) was the first CDK4/6 inhibitor to reach the market, approved by the FDA in 2015 to treat advanced breast cancer. (xconomy.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)
  • Ribociclib is a selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. (medscape.com)
  • These results affirm that combination therapy with a CDK4/6 inhibitor like ribociclib and an aromatase inhibitor should be a new standard of care for initial treatment of HR+ advanced breast cancer," said Gabriel N. Hortobagyi, MD, from the University of Texas MD Anderson Cancer Center in Houston and a MONALEESA-2 principal investigator, in the statement. (medscape.com)
  • NVS ) CDK4/6 inhibitor ribociclib (Kisqali) for advanced breast cancer. (xconomy.com)
  • In contrast, IL-6 failed to induce p21WAF1/CIP1 transcript and did not increase p21WAF1/CIP1 or p27kip1 proteins in any of the resistant lines. (nih.gov)
  • Once bound to a cyclin they act to phosphorylate many target proteins on serine or threonine amino acid residues. (news-medical.net)
  • Each interacts with a different cyclin at a different phase, stimulating various target proteins and ensuring that vital stages of each phase are carried out before a cell moves onto the next phase. (news-medical.net)
  • The myeloma drug lenalidomide promotes the cereblon-dependent destruction of ikaros proteins. (nature.com)
  • Borne out of motivation to better understand the nature of protein degradation, pioneering studies elucidated a multistep ATP-dependent enzymatic cascade by which ubiquitin is conjugated to proteins, marking them for degradation [ 7 ]. (biochemj.org)
  • METHODS: We studied how two structurally distinct forms of type I collagen, monomer versus polymerized fibrils, affect cell proliferation, mitogen-activated protein kinase (MAPK) activation, and expression of G1-phase regulatory proteins in cultured rat mesangial cells (MCs). (biomedsearch.com)
  • Ukoniq (umbralisib) is a dual inhibitor of phosphoinositide 3 kinase (PI3K). (drugs.com)
  • In contrast, CDK1 inactivation significantly induced apoptosis and reduced viability of MYC-dependent cells but not MYC- independent cells. (biomedcentral.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)
  • Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. (wikipedia.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)
  • APC/C then drives the process forward as it subsequently targets Ase1 and cyclin B for destruction ( Peters 1999 ). (rupress.org)
  • is a human monoclonal antibody that targets the interleukin-6 receptor and is licensed for the treatment of moderate to severe active rheumatoid arthritis. (medicinescomplete.com)
  • The first mechanism is based on increased androgen receptor signaling caused by mutations in the AR that allow it to be activated by ligands other than DHT or by signaling pathways induced by a tyrosine kinase receptor, such as Her/2neu ( 5 , 6 ). (pnas.org)
  • No mutations showed up in exon 6 of 390 further British and Australian controls. (alzforum.org)
  • All mutations are in exon 6, so it raises the hypothesis that there's something particular about that part of the protein that will affect processing or some other important aspect," Mackenzie said. (alzforum.org)
  • Verzenio is a cyclin-dependent kinase (CDK)4 & 6 inhibitor that will be available as 50, 100, 150 and 200 mg tablets. (thefreedictionary.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)
  • Based on these observations, cyclin D-dependent kinases have been considered for many years a prime target for cancer chemotherapy ( 22 , 23 ). (aacrjournals.org)
  • These observations lend credence to Cdk4/6 as a target for cancer treatment and allow a reasonable expectation that a specific inhibitor of these enzymes would produce a meaningful therapeutic response. (aacrjournals.org)
  • Targeting cyclins and cyclin-dependent kinases in cancer: lessons from mice, hopes for therapeutic applications in human. (thefreedictionary.com)
  • The report provides a competitor evaluation in the field of synthetic molecules targeting polo-like kinase 1 (Plk-1), cyclin-dependent kinase (CDK) or aurora kinase for treatment of cancer as of September 2011. (thefreedictionary.com)
  • 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)
  • Taken together, our data support the rationale for clinical development of the CDK4/6 inhibitor as a therapy for patients with aggressive thyroid cancer. (yonsei.ac.kr)
  • Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor-positive (ER + ) breast cancer. (elsevier.com)
  • 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)
  • The study was presented on Dec. 6, 2017 at the 2017 San Antonio Breast Cancer Symposium. (breastcancer.org)
  • 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)
  • We have shown that the Aurora kinase inhibitor VX-680 induces endoreduplication and eventual cell death in cancer cells. (dana-farber.org)
  • It would only be for patients with cancer that does not depend on the CDK4/6 enzymes. (xconomy.com)
  • Cytoplasmic Cyclin E Expression Predicts for Response to Neoadjuvant Chemotherapy in Breast Cancer. (mdanderson.org)
  • Liver cancer is ranked in the top 10 human cancers worldwide and among the top five of cancers in terms of mortality [ 5 , 6 , 7 ]. (mdpi.com)
  • In contrast to mammalian cells, these yeast cells had only one CDK which interacted with various cyclins. (news-medical.net)
  • Here, we discuss our findings and the Cyclin D2 function in mammalian brain development and evolution. (wiley.com)
  • As one example, we have only recently learned that loss of the platelet-derived growth factor (PDGF) receptor-α in adult human β-cells, with the resultant loss of ability to activate mitogen-activated protein kinase and methylation (Ezh2) and downstream cell cycle (p16) machinery, may underlie the refractoriness of human β-cells to proliferation ( 16 ). (diabetesjournals.org)
  • Abemaciclib with continuous dosing v.s 3 weeks on 1 off for the others CDK4/6, abemaciclib does have less severe neutropenia. (her2support.org)
  • In this study, we examined the effect of IL-6 on LNCaP human prostate carcinoma cells. (nih.gov)
  • Human melanoma cell lines derived from early stage primary tumors are particularly sensitive to growth arrest induced by interleukin-6 (IL-6). (nih.gov)
  • This is particularly surprising because in contrast to the intractable quiescence of adult human β-cells, fetal and neonatal human β-cells can and do replicate transiently from ~5 months antepartum to ~6 months postpartum ( 13 - 15 ). (diabetesjournals.org)
  • "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C" . Proceedings of the National Academy of Sciences of the United States of America . (wikipedia.org)
  • RT "A family of human cdc2-related protein kinases. (genome.jp)
  • RT "Cyclin-dependent kinase 6 inhibits proliferation of human mammary RT epithelial cells. (genome.jp)
  • a total of 2,588 human genome miRNAs are included in the miRBase database ( 6 ). (spandidos-publications.com)
  • Generating homozygous and hemizygous WT human TDP-43 transgenic mouse lines, we show here a dose-dependent degeneration of cortical and spinal motor neurons and development of spastic quadriplegia reminiscent of ALS. (pnas.org)
  • 5 ]]. With around 10-20,000 Mb [ 6 ], conifer genomes are more than 100 times larger than that of Arabidopsis and three times larger than the human genome. (biomedcentral.com)
  • A similar localization pattern of Cyclin D2 protein has been observed in the human fetal cortical primordium, suggesting a common mechanism of maintenance of neural progenitors that may be evolutionarily conserved across higher mammals such as primates. (wiley.com)
  • It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18. (curehunter.com)
  • In addition to its role in cell cycle control, cyclin D1 also binds to and activates the estrogen receptor ( 11 ) but binds to and inhibits the activity of the AR ( 12 , 13 ). (pnas.org)
  • CDK11(p58) kinase activity is required to protect sister chromatid cohesion at centromeres in mitosis. (nih.gov)
  • 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)
  • Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (wikipedia.org)
  • We hypothesized that this dual activity of silvestrol would make it especially effective in malignancies driven by aberrant cyclin D1 expression. (aacrjournals.org)
  • Moreover, polymerized type I collagen markedly reduced cyclin E-associated kinase activity in the presence of 5% FCS. (biomedsearch.com)
  • The Activation of IL-1-Induced Enhancers Depends on TAK1 Kinase Activity and NF-κB p65. (mh-hannover.de)
  • is a phosphoinositide-3 kinase (PI3K) inhibitor that is licensed for the treatment of relapsed follicular lymphoma. (medicinescomplete.com)
  • Cyclin D3 promotes pancreatic β-cell fitness and viability in a cell cycle-independent manner and is targeted in autoimmune diabetes. (semanticscholar.org)
  • PI3 kinase is an enzyme important in cell growth. (komen.org)
  • They provide all the optimized components (enzyme, preferred substrate, required cofactors, buffer) that you need to generate a kinase selectivity profile for a compound. (promega.com)
  • Below each tab is a list of currently available Kinase Enzyme Systems (or those coming soon). (promega.com)
  • Click on any enzyme for additional information (such as Applications Note, the Catalog Page, or the NCBI Database entry) for that kinase. (promega.com)
  • Mantle cell lymphoma (MCL), characterized by elevated cyclin D1, was used as a model to test this approach. (aacrjournals.org)
  • The PI3 kinase inhibitor taselisib in combination with the hormone therapy drug letrozole is under study for the treatment of estrogen receptor-positive, HER2-negative early breast cancers in the neoadjuvant (before surgery) setting [ 57 ]. (komen.org)
  • A second G1 drug, G1T38, is in development for cancers that depend on the CDK4/6 enzymes. (xconomy.com)
  • A separate Phase 2 trial in patients whose breast cancers are dependent on CDK4/6 is also expected to start next year. (xconomy.com)
  • Modelling of Protein Kinase Signaling Pathways in Melanoma and Other Cancers. (wikipathways.org)
  • We show here that overexpression of WT TDP-43 leads to degeneration of specific neurons in the central nervous system, including spinal and cortical motor neurons and nonmotor cortical neurons characteristically affected in FTLD-TDP, and causes spastic quadriplegia in a dose-dependent manner. (pnas.org)
  • Interleukin-6 induces G1 arrest through induction of p27(Kip1), a cyclin-dependent kinase inhibitor, and neuron-like morphology in LNCaP prostate t. (nih.gov)
  • Thus, IL-6-induced G1 arrest appears to be due to the accumulation of p27(Kip1). (nih.gov)