Cyclin-Dependent Kinases: 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.Cyclin-Dependent Kinase 2: 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.Cyclin D1: 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.Cyclin A: 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.Cyclin E: A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.Cyclins: 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: Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.CDC2-CDC28 Kinases: 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.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Cyclin-Dependent Kinase Inhibitor p21: 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.Cyclin-Dependent Kinase 5: 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.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Cyclin B: 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.Cyclin C: 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.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.CDC2 Protein Kinase: Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.Cyclin D: 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.G1 Phase: 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.Cyclin-Dependent Kinase Inhibitor p16: A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.Cyclin-Dependent Kinase Inhibitor Proteins: 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.Cyclin D3: A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.Cyclin B1: A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.Phosphorylation: 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: Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.Cyclin-Dependent Kinase Inhibitor p57: 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.Tumor Suppressor Proteins: 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.S Phase: 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.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Cyclin D2: 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.Cyclin A1: A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.Microtubule-Associated Proteins: 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.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Purines: 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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Proto-Oncogene Proteins: 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.E2F1 Transcription Factor: 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.Cyclin A2: A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Cyclin G: A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.Cell Line, Tumor: A cell line derived from cultured tumor cells.Tumor Cells, Cultured: 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.Tumor Suppressor Protein p53: 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.Mitosis: 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.Cyclin G1: 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.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.Transcription Factor DP1: 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.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Cells, Cultured: 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.Blotting, Western: 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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.G2 Phase: 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.E2F Transcription Factors: A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.Transfection: 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.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)Mutation: 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.Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Cell Line: Established cell cultures that have the potential to propagate indefinitely.DNA-Binding Proteins: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Nuclear Proteins: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.src-Family Kinases: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Reverse Transcriptase Polymerase Chain Reaction: 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.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Amino Acid Sequence: 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.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.Cyclic AMP-Dependent Protein Kinases: 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.Cyclin B2: 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.Mitogen-Activated Protein Kinase 1: 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.Protein Binding: 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.Enzyme Activation: 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.Gene Expression Regulation: 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.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Cyclin T: 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.Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.p21-Activated Kinases: 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.Mitogen-Activated Protein Kinase 3: 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.JNK Mitogen-Activated Protein Kinases: 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-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Cyclin H: 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.Cyclin G2: 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.Kinetics: The rate dynamics in chemical or physical systems.Calcium-Calmodulin-Dependent Protein Kinase Type 2: A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.MAP Kinase Kinase Kinases: 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 Fusion Proteins: 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.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Creatine Kinase: A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.Models, Biological: 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.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Casein Kinase II: 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.eIF-2 Kinase: A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Ribosomal Protein S6 Kinases: A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).MAP Kinase Kinase 1: An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Down-Regulation: 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.Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.Casein Kinases: A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.Serine: 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.Pyruvate Kinase: 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.Glycogen Synthase Kinase 3: 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.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Promoter Regions, Genetic: 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.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Thymidine Kinase: 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.MAP Kinase Kinase 4: 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.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Saccharomyces cerevisiae Proteins: 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.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.I-kappa B Kinase: 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.Mice, Inbred C57BLProto-Oncogene Proteins c-akt: 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.E2F4 Transcription Factor: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.DNA Primers: 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.1-Phosphatidylinositol 4-Kinase: 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.Aurora Kinases: A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.rho-Associated Kinases: A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.Protein Kinase C-alpha: 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.DNA Replication: The process by which a DNA molecule is duplicated.HeLa Cells: 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.S Phase Cell Cycle Checkpoints: 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.Protein Kinase C-delta: 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.Saccharomyces cerevisiae: 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.PhosphoproteinsRats, Sprague-Dawley: 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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Oncogene Proteins: Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.AMP-Activated Protein Kinases: Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.Immunoblotting: 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.Cyclin I: 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.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Diacylglycerol Kinase: An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.Precipitin Tests: 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.Retinoblastoma-Binding Protein 1: 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.Focal Adhesion Kinase 1: A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Janus Kinase 2: A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Myosin-Light-Chain Kinase: An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.Focal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.Ribosomal Protein S6 Kinases, 90-kDa: A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.TOR Serine-Threonine Kinases: A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.Neurons: 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.Threonine: 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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Cloning, Molecular: 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.ChromonesProtein Kinase C-epsilon: A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.Cyclic AMP: 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.MAP Kinase Kinase 2: A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.MAP Kinase Kinase Kinase 1: 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.Cell Survival: 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.Up-Regulation: 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.Genes, bcl-1: 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.Breast Neoplasms: Tumors or cancer of the human BREAST.Protein Kinase C beta: PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.MorpholinesGene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Protein Transport: 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.Membrane Proteins: 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.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Adenosine Triphosphate: 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.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesPhosphoprotein Phosphatases: 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)Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Genes, p16: Tumor suppressor genes located on human chromosome 9 in the region 9p21. This gene is either deleted or mutated in a wide range of malignancies. (From Segen, Current Med Talk, 1995) Two alternatively spliced gene products are encoded by p16: CYCLIN-DEPENDENT KINASE INHIBITOR P16 and TUMOR SUPPRESSOR PROTEIN P14ARF.Mitogen-Activated Protein Kinase 8: 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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Phosphoglycerate Kinase: 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.Casein Kinase I: A casein kinase that was originally described as a monomeric enzyme with a molecular weight of 30-40 kDa. Several ISOENZYMES of casein kinase I have been found which are encoded by separate genes. Many of the casein kinase I isoenzymes have been shown to play distinctive roles in intracellular SIGNAL TRANSDUCTION.NF-kappa B: 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.MAP Kinase Kinase 6: A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 ...
... cellular proliferation via inhibition of CDK activities. routine and g27Kip1 (hereafter g27) can regulate CDK actions.1-3 The p27 protein was originally known as an inhibitor of CDK activities for things containing CDK2 and shown to inhibit cyclin E and cyclin A activities which regulate G1 and S phase traverse.4-6 In addition to CDK inhibition, g27 provides other multifarious connections with cyclin N/cdk4 processes putatively.7 Since cellular amounts of g27 are elevated in response to high cell thickness, serum deprival, and TGF, it was hypothesized g27 brought cells into quiescence and held them in G0 through the inhibition of CDK actions.8 Numerous reviews have got characterized the control of p27 including the control of its transcription,9,10 translation,11,12 post-translational adjustments.7,13,14 cellular localization15-19 and balance.20-23 The regulations of its stability has a main role in adjusting mobile ...
Recombinant Cyclin-Dependent Kinase 10 (CDK10) Protein (His tag). Species: Cow (Bovine). Source: Yeast. Order product ABIN1616360.
Recombinant Cyclin-Dependent Kinase 10 (CDK10) Protein (His tag). Species: Human. Source: Insect Cells. Order product ABIN3091398.
View mouse Cdk11b Chr4:155624854-155649938 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
pep:known chromosome:VEGA66:5:146231288:146302874:1 gene:OTTMUSG00000025856 transcript:OTTMUST00000063710 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Cdk8 description:cyclin-dependent kinase 8 ...
Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
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p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
P 276 is a flavone that selectively inhibits the cyclin-dependent kinases Cdk4-D1, Cdk9-T and Cdk1-B, thus inhibiting the pathways necessary for cancer cell
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Complete information for CDK4 gene (Protein Coding), Cyclin Dependent Kinase 4, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for CDK18 gene (Protein Coding), Cyclin Dependent Kinase 18, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
NU2058 (O6-(Cyclohexylmethyl)guanine) is a potent, competitive and guanine-based CDK inhibitor with IC50s of 17 μM and 26 μM for CDK2 and CDK1. NU2058 has anti-cancer activity. - Mechanism of Action & Protocol.
1GIH: Crystallographic approach to identification of cyclin-dependent kinase 4 (CDK4)-specific inhibitors by using CDK4 mimic CDK2 protein.
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Your Search Returned No Results.. Sorry. There is currently no product that acts on isoform together.. Please try each isoform separately.. ...
The randomised controlled trial (RCT) is the gold standard for evaluating the effects of health care interventions.1 Therefore, South African health policy and clinical guidelines should be based on well-conducted RCTs that ideally are conducted within the country to ensure local applicability. Conducting RCTs in South Africa faces numerous obstacles. Specialist training in the universities traditionally focuses on clinical experience and skills accrual, and lacks a research focus. Downscaled tertiary service units struggle to remain academically active,2 reducing the opportunities for local clinicians to acquire the epidemiological and statistical skills for conducting RCTs. Health professionals interested in clinical research may have to migrate to develop these skills. Opportunities to then practise those skills may only exist overseas, contributing to the professional brain drain.3 When research funding is not available from local sources, researchers become dependent on funds from donor ...
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.
Dinaciclib, also known as SCH727965, is a potent CDK inhibitor with potential antineoplastic activity. Dinaciclib selectively inhibits cyclin dependent kinases CDK1, CDK2, CDK5, and CDK9 activity in vitro with IC(50) values of 1, 1, 3, and 4 nmol/L, respectively. Compared with flavopiridol, Dinaciclib exhibits superior activity with an improved therapeutic index. Dinaciclib induced regression of established solid tumors in a range of mouse models following intermittent scheduling of doses below the maximally tolerated level..
1KE9: Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis.
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Cdk5r1 - Cdk5r1 (Myc-DDK-tagged ORF) - Rat cyclin-dependent kinase 5, regulatory subunit 1 (p35) (Cdk5r1), (10 ug) available for purchase from OriGene - Your Gene Company.
Cdk14 - Cdk14 (Myc-DDK-tagged) - Mouse cyclin-dependent kinase 14 (Cdk14) available for purchase from OriGene - Your Gene Company.
Looking for online definition of cyclin-dependent kinase 15 in the Medical Dictionary? cyclin-dependent kinase 15 explanation free. What is cyclin-dependent kinase 15? Meaning of cyclin-dependent kinase 15 medical term. What does cyclin-dependent kinase 15 mean?
TY - JOUR. T1 - SU9516, a cyclin-dependent kinase 2 inhibitor, promotes accumulation of high molecular weight E2F complexes in human colon carcinoma cells. AU - Yu, Bo. AU - Lane, Maureen E.. AU - Wadler, Scott. PY - 2002/10/1. Y1 - 2002/10/1. N2 - The E2F family plays a critical role in the expression of genes required for entry into and progression through S phase. E2F-mediated transcription is repressed by the tumor suppressor retinoblastoma protein (pRb), which results in sequestration of E2F in a multiprotein complex that includes pRb. Derepression of E2F results from a series of complex phosphorylation events mediated by cyclin D/cdk4 and cyclin E/cdk2. We have employed a novel 3-substituted indolinone compound, 3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516), which selectively inhibits cdk2 activity (Lane et al., Cancer Res 2001;61:6170-7) to investigate these events. Electrophoretic mobility gel shift assays were performed on SU9516-treated and ...
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If you have a question about this talk, please contact Caroline Newnham.. Host: Viji Draviam. Tissue homeostasis in metazoans is regulated by transitions of cells between quiescence and proliferation. The hallmark of proliferating populations is progression through the cell cycle, which is driven by Cyclin-dependent kinase (CDK) activity. I will discuss our recent development of a live-cell sensor for CDK2 activity and the finding that proliferating cells bifurcate into two populations as they exit mitosis. Some cells immediately commit to the next cell cycle by building up CDK2 activity from an intermediate level, while other cells lack CDK2 activity and enter a transient state of quiescence. This bifurcation is directly controlled by the CDK inhibitor p21 and is regulated by mitogens during a restriction window at the end of the previous cell cycle. We are currently exploring the role of cell stress in controlling this bifurcation in an attempt to uncover the root cause of this striking ...
Cyclin-dependent kinases (CDKs) are core components of the cell cycle machinery that govern the transition between phases during cell cycle progression. Genes involved in cell cycle are frequently mutated in human cancer and deregulated CDK activity repr
The researchers examined a protein called cyclin-dependent kinase 2 (CDK2), which works as a "quality control inspector." As normal cells divide, they pause in the replication process when they find inaccurate genetic code embedded in their DNA. The health and well-being of offspring cells depends on accurate genetic code transfer from one generation of cells to the next. The Mayo researchers showed that when errors in genes are irreparable, CDK2 modifies another cellular protein -- FOXO1 -- to send a signal that results in the death of the cell. This protein-to-protein relationship invites targeted drug intervention to control unregulated growth of cancer cells ...
HMN-214 inhibits polo-like and cyclin-dependent kinase activity, has potent antimicrotubular effects and results in profound apoptosis and antitumor activity in a broad spectrum of human xenografts.
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A stable environment minimizes evapora- tive heat loss. 10. Cyclin-dependent kinases participate recomendaad death of neurons evoked by DNA- damaging agents. Daleiden, A.
The i-CDK9-induced increase in CDK9s binding to the MYC locus is mostly BRD4-dependent.DOI:http://dx.doi.org/10.7554/eLife.06535.017
Cyclin D-Cdk4 complexes have a demonstrated role in G1 phase, regulating the function of the retinoblastoma susceptibility gene product (Rb). Previously, we have shown that following treatment with low doses of UV radiation, cell lines that express wild-type p16 and Cdk4 responded with a G2 phase cell cycle delay. The UV-responsive lines contained elevated levels of p16 post-treatment, and the accumulation of p16 correlated with the G2 delay. Here we report that in UV-irradiated HeLa and A2058 cells, p16 bound Cdk4 and Cdk6 complexes with increased avidity and inhibited a cyclin D3-Cdk4 complex normally activated in late S/early G2 phase. Activation of this complex was correlated with the caffeine-induced release from the UV-induced G2 delay and a decrease in the level of p16 bound to Cdk4. Finally, overexpression of a dominant-negative mutant of Cdk4 blocked cells in G2 phase. These data indicate that the cyclin D3-Cdk4 activity is necessary for cell cycle progression through G2 phase into mitosis and
Vol 7: PD-0332991 induces G1 arrest of colorectal carcinoma cells through inhibition of the cyclin-dependent kinase-6 and retinoblastoma protein axis.. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Recombinant human CDKN1B protein, fused to His-tag at N-terminus, was expressed in E. coli and purified by using conventional chromatography. MW: 24.2 kDa.
MONARCH 1: Final overall survival analysis of a phase 2 study of abemaciclib, a CDK4 and CDK6 inhibitor, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for advanced ...
CDK4 and CDK6, which drive cell cycle entry and progression through G1 in the presence of cyclin D, are overexpressed at a high frequency in human cancers. Targ...
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Novel localization of Argonaute 2 (AGO2) to human mitochondria.A. Purity assessment of mitochondrial fraction. Cyclin-dependent kinase 2 (CDK2) was assessed in
Inhibition of CDK4-6 as a novel therapeutic option for neuroblastoma. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
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Looking for online definition of Cyclin-dependent Kinase-like 3 in the Medical Dictionary? Cyclin-dependent Kinase-like 3 explanation free. What is Cyclin-dependent Kinase-like 3? Meaning of Cyclin-dependent Kinase-like 3 medical term. What does Cyclin-dependent Kinase-like 3 mean?
[51 Pages Report] Check for Discount on Cyclin-Dependent Kinase 1 (p34 Protein Kinase or Cell Division Protein Kinase 1 or CDK1 or EC 2.7.11.22) - Pipeline Review, H1 2016 report by Global Markets Direct. Global Markets Directs, Cyclin-Dependent Kinase 1 (p34 Protein...
Cardiac hypertrophy leading to heart failure remains a leading cause of morbidity and mortality in the 21st century despite major therapeutic advances. Improved understanding of novel molecular and cellular processes contributing to cardiac hypertrophy therefore continues to be important. Cyclin-dependent Kinase 9 (CDK9), part of a family of proteins controlling cell cycle and growth, has emerged as one such potential candidate over the last 5 years. CDK9 is the catalytic subunit of the CDK9/CyclinT complex and acts by phosphorylating the carboxy-terminal domain of RNA polymerase II. Hypertrophic signals, such as Endothelin-1 (ET-1) and phenylephrine, have been shown to cause CDK9 activation leading to a hypertrophic response in cultured mouse cardiomyocytes associated with reactivation of the foetal gene program. CDK9 also forms a complex with GATA4 to play a role in differentiation of mouse ES cells into cardiomyocytes. These findings suggest a specific role for CDK9 in controlling growth and ...
Background Over the last decade a number of species, from farm animals to rodents, have been cloned using somatic cell nuclear transfer technology (SCNT). This technique has the potential to revolutionize the way that genetically modified animals are made. In its current state, the process of SCNT is very inefficient (|5% success rate), with several technical and biological hurdles hindering development. Yet, SCNT provides investigators with powerful advantages over other approaches, such as allowing for prescreening for the desired level of transgene expression and eliminating the excess production of undesirable wild-type animals. The rat plays a significant role in biomedical research, but SCNT has been problematic for this species. In this study, we address one aspect of the problem by evaluating methods of activation in artificially constructed rat embryos. Principal Findings We demonstrate that treatment with a calcium ionophore (ionomycin) combined with a variety of cyclin-dependent kinase
p35 is an activating co-factor of Cyclin-dependent kinase 5 (Cdk5), a protein whose dysfunction has been implicated in a wide-range of neurological disorders including cognitive impairment and disease. Inducible deletion of the p35 gene in adult mice results in profound deficits in hippocampal-dependent spatial learning and synaptic physiology, however the impact of the loss of p35 function on hippocampal in vivo physiology and spatial coding remains unknown. Here, we recorded CA1 pyramidal cell activity in freely behaving p35 cKO and control mice and found that place cells in the mutant mice have elevated firing rates and impaired spatial coding, accompanied by changes in the temporal organization of spiking both during exploration and rest. These data shed light on the role of p35 in maintaining cellular and network excitability and provide a physiological correlate of the spatial learning deficits in these mice.
A8326 AZD-5438 AZD5438 is a potent small molecule inhibitor of cyclin-dependent kinase (CDK) 1, 2 and 9 with half maximal inhibitory concentration IC50 of 16 nmol/L, 6 nmol/L and 20 nmol/L respectively. AZD5438 has also been found to potently inhibit the human cyclin E/CDK2 complex, the cyclin B1/CDK1 complex and the cyclin A/CDK2 complex with IC50 of 0.006 μM, 0.016 μM and 0.045 μM respectively. In previous studies, AZD5438 has exhibited significant anti-proliferative activity in a few human tumor cell lines with IC50 ranging from 0.2 μmol/L to 1.7 μmol/L, in which the phosphorylation of a few proteins, including CDK substrates pRb, nucleolin, protein phosphatase 1a and RNA polymerase II COOH-terminal domain, and cell cycling at G2-M, S and G1 phases were inhibited. ...
The NF-κB transcription factor is one of the most important regulators of the cellular life/death balance and its aberrant activation is associated with cancer ( 4). Therefore, identifying mechanisms for switching off aberrant NF-κB activity could have a major therapeutic benefit. Here, we reveal a novel pathway for down-regulating NF-κB transcriptional activity and inducing apoptosis of colon cancer cells that involves activation of the p38 pathway, inhibition of the cyclin D1/CDK4 kinase complex, and consequent nucleolar targeting of RelA. These findings contribute to our knowledge of the complexities of NF-κB signaling. Furthermore, these findings have considerable relevance to understanding the mechanisms of chemoprevention and cancer therapeutics.. The data presented here provide evidence that p38-mediated inhibition of cyclin D1/CDK4 stimulates the NF-κB pathway to induce nucleolar sequestration of RelA. This conclusion is based on the following findings. First, p38 was rapidly ...
DESCRIPTION (provided by applicant): This Phase II SBIR project is aimed at developing a novel type of drugs, termed SNX9-class compounds, with a unique combination of two anticancer activities. The first is a selective antiproliferative effect on tumor cells relative to normal cells. The second is the inhibition of chemotherapy- or radiation-induced expression of multiple genes encoding secreted tumor-supporting factors with mitogenic, antiapoptotic and angiogenic activities; as a result, SNX9-class compounds potentiate the induction of apoptosis by conventional chemotherapeutic drugs. Studies conducted during Phase I of this project showed that both activities of SNX9- class compounds are due to their ability to inhibit CDK3. This understudied member of the cyclin-dependent kinase (CDK) family is apparently unneeded by normal cells, based on its very low expression in normal human tissues and spontaneous germline inactivation in laboratory mice. However, CDK3 is overexpressed in different ...
Cyclin-dependent kinase 4 (CDK4) is a member of cyclin-dependent kinase family which regulates G1 to S cell cycle transition. CDK4 activity is increased in many tumor types. Here, we report a...
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CDK8 antibody (cyclin-dependent kinase 8) for ICC/IF, IP, WB. Anti-CDK8 pAb (GTX22955) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
CDK3 antibody [N1C2] (cyclin-dependent kinase 3) for WB. Anti-CDK3 pAb (GTX105047) is tested in Human samples. 100% Ab-Assurance.
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Cyclin-dependent kinases (CDKs) are a family of sugar kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They are present in all known eukaryotes, and their regulatory function in the cell cycle has been evolutionarily conserved. In fact, yeast cells can proliferate normally when their CDK gene has been replaced with the homologous human gene. CDKs are relatively small proteins, with molecular weights ranging from 34 to 40 kDa, and contain little more than the kinase domain. By definition, a CDK binds a regulatory protein called a cyclin. Without cyclin, CDK has little kinase activity; only the cyclin-CDK complex is an active kinase. CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases. The consensus sequence for the phosphorylation site in the amino acid sequence of a CDK substrate is [S/T*]PX[K/R], where S/T* is the ...
In contrast to cyclin D1 and D2, the expression level of cyclin D3 was high in the hindbrain at the E15.5 stage (Figure 3I, arrowhead). Moreover, in the midbrain cyclin D3 was expressed in cells closer to the ventricle than those expressing cyclin D2 (Figure 3H, I, arrows).. Discussion. At the E10.5 stage, all three D-type cyclins were expressed in most of the spinal cord cells but cyclin D1 and D3 showed higher expression levels in the dorsal half of the spinal cord. Wianny et al. (1998) found that the dorso-ventral gradient of the cyclin D1 transcript also occurs in the spinal cord of 7-9 somite-stage embryos. However, in our study we found that at the E10.5 stage cyclin D2 was not missing from the floor plate and also that cyclin D3 was not expressed only ventrally, as was reported for the transcripts of the genes in 7-9 somite stage embryos by Wianny et al. (1998). This may have been due to altered expression patterns of these genes during the time course of spinal cord development and ...
2604 We demonstrate that Smad3, a key mediator of TGF-beta antiproliferative responses, is a major physiological substrate of G1 cyclin-dependent kinases CDK4 and CDK2. Except for the retinoblastoma protein (Rb) family, Smad3 is the only substrate demonstrated so far for CDK4, and Smad3 can be phosphorylated by CDK4 to a greater extent than Rb. We have mapped both the in vivo and the in vitro CDK4 and CDK2 phosphorylation sites in Smad3. These sites are phosphorylated by CDK4 and CDK2 in vitro and in a cell-cycle dependent manner in vivo. Moreover, we show that their phosphorylation is reduced in CDK4 knockout mouse embryonic fibroblasts (MEF), and their phosphorylation is increased in CDK4 R24C/R24C MEF, which have elevated CDK4 activity. In addition, RNAi experiments also indicate that CDK4 and CDK2 phosphorylate these sites. CDK phosphorylation of Smad3 inhibits its basal as well as TGF-beta induced transcriptional activity, thus preventing activation of the expression of CDK inhibitors p15 ...
Schematic of the cell cycle. outer ring: I=Interphase, M=Mitosis; inner ring: M=Mitosis; G1=Gap phase 1; S=Synthesis; G2=Gap phase 2. The duration of mitosis in relation to the other phases has been exaggerated in this diagram Cyclin dependent…
The KOMP Repository Collection is located at the MMRRC at the University of California, Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
D-type cyclins (cyclin D1, D2 and D3) are components of the core cell cycle machinery. Rearrangements of cyclin D genes and overexpression of cyclin D proteins...
The cell cycle is under strict regulation. Cyclin-dependent kinases (CDKs) at the G1-S and G2-M checkpoints are positively regulated by cyclins and negatively regulated b..
Rabbit recombinant monoclonal CDK1+Cdk2+Cdk3+Cdk5 antibody [E53] validated for WB, IP, ICC/IF and tested in Human. With 1 independent review.
The p57(Kip2) cyclin-dependent kinase inhibitor (CDKi) has been implicated in embryogenesis, stem-cell senescence and pathologies, but little is known of its role in cell cycle control. Here, we show that p57(Kip2) is ...
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Plasmid pCMV HA hRB delta CDK + S608 from Dr. Steven Dowdys lab contains the insert Rb and is published in Elife. 2014 May 29:e02872. doi: 10.7554/eLife.02872. This plasmid is available through Addgene.
Growth Inhibition in MC/CAR Myeloma Cells via Cell Cycle Arrest in Association with Induction of Cyclin-dependent Kinase ... and protein kinase RNA-like endoplasmic reticulum kinase (PERK) are two receptors that restrict the rate of translation.[61] On ... Sykora, P; Snow, E.T (2008). "Modulation of DNA polymerase beta-dependent base excision repair in cultured human cells after ... Phosphate-Dependent Organism". Science. 337 (6093): 467-70. Bibcode:2012Sci...337..467E. doi:10.1126/science.1218455. PMID ...
negative regulation of cyclin-dependent protein serine/threonine kinase activity. • lung development. • cytokine-mediated ... kinase binding. • GO:0001948 protein binding. • GO:0000975 transcription regulatory region DNA binding. • transcription factor ... positive regulation of proteasomal ubiquitin-dependent protein catabolic process. • positive regulation of transcription from ... 4] Довжина поліпептидного ланцюга білка становить 358 амінокислот, а молекулярна маса - 37 561[5]. ...
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 ...
... leading to an accumulation of cyclin-dependent kinase inhibitors p21 and p27, and to subsequent G1-phase arrest, as seen in ... Bobek P, Ozdín L, Galbavý S (1998). "Dose- and time-dependent hypocholesterolemic effect of oyster mushroom (Pleurotus ... "Effect of the oyster fungus on glycaemia and cholesterolaemia in rats with insulin-dependent diabetes". Physiol Res. 42 (3): ... 1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-Hydroxy-6-oxooxan-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (2S)-2- ...
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 ...
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 ...
CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) Archived 2004-11-17 at the Wayback Machine from ... Another mutation in the same gene results in a nonfunctional inhibitor of CDK4, a cyclin-dependent kinase that promotes cell ... molecular weight protein inhibitor of cyclin-dependent protein kinases (CDKs) - which has been localised to the p21 region of ... 18 (4): 351-357. doi:10.1080/14737167.2018.1467270. PMID 29681201.. *^ a b c d West HJ (April 2015). "JAMA Oncology Patient ...
SLBP are marked for degradation by phosphorylation at two threonine residues by cyclin dependent kinases, possibly cyclin A/ ... 85 (4): 435-43. doi:10.1139/o07-057. PMID 17713579.. *^ a b c d e f g h Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z ... "NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription". Genes & Development. 14 (18): ... The mitotic kinase aurora B phosphorylates histone H3 at serine 10, triggering a cascade of changes that mediate mitotic ...
protein kinase activity. • cAMP-dependent protein kinase activity. • ADP binding. • AMP-activated protein kinase activity. • ... cAMP-dependent protein kinase regulator activity. • protein kinase binding. • ATP binding. • adenyl ribonucleotide binding. ... 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 ...
"Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated ... "HDAC1, HDAC4, and HDAC9 Bind to PC3/Tis21/Btg2 and Are Required for Its Inhibition of Cell Cycle Progression and Cyclin D1 ... protein kinase binding. • hydrolase activity. • protein deacetylase activity. • identical protein binding. • core promoter ... NAD-dependent histone deacetylase activity (H3-K14 specific). • sequence-specific DNA binding. • DNA binding. • transcription ...
The catalytic subunit of cAMP-dependent protein kinase: prototype for an extended network of communication.. „Prog Biophys Mol ... Shanahan F, Seghezzi W, Parry D, Mahony D, Lees E. Cyclin E associates with BAF155 and BRG1, components of the mammalian SWI- ... LKB1, a novel serine/threonine protein kinase and potential tumour suppressor, is phosphorylated by cAMP-dependent protein ... LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. „EMBO J". 23. 4, s. 833-43, 2004 ...
NUCKS1: Nuclear ubiquitous casein and cyclin-dependent kinases substrate. *NVL: Nuclear valosin-containing protein-like ... C1orf103: encoding protein Ligand-dependent nuclear receptor-interacting factor 1 (LRIF1). *C1orf109: chromosome 1 open reading ... G-banding patterns of human chromosome 1 in three different resolutions (400,[15] 550[16] and 850[4]). Band length in this ... UBR4: E3 ubiquitin-protein ligase component n-recognin 4. *UROD: uroporphyrinogen decarboxylase (the gene for porphyria cutanea ...
... is inhibited by cyclin dependent kinases (CDKs). CDKs are in turn inhibited by p21. Thus MyoD enhances its own activity in ... Both MyoD and pRb are necessary for the repression of cyclin D1, but rather than acting directly on cyclin D1, they act on Fra- ... "Coupling of the cell cycle and myogenesis through the cyclin D1-dependent interaction of MyoD with cdk4". EMBO J. 18 (4): 926- ... Cyclin D1. Cell cycle arrest (in which myoblasts would indicate the conclusion of myogenesis) is dependent on the continuous ...
사이클린 의존성 인산화효소(Cyclin-dependent Kinase; CDKs)는 세포주기 조절과 관련된 인산화효소들이다. 다른 단백질의 세린 혹은 트레오닌 잔기를 인산화하지만, 반드시 사이클린 단백질과 먼저 결합하여야 활성을 ... Harper, J. W.; Adams, P. D. (2001년 8월). "Cyclin-Dependent Kinases". Chemical Reviews (영어) 101 (8): 2511-2526. doi:10.1021/ ... Canavese, Miriam; Santo, Loredana; Raje, Noopur (2012년 5월 1일). "Cyclin dependent kinases in cancer: Potential for therapeutic ... 유사분열 활성화 단백질 인산화효소(Mitogen-Activated Protein Kinases; MAP kinase; MAPKs)는 세린/트레오닌 인산화효소족으로 다양한 세포외 성장 신호에 반응한다. 성장 호르몬이나 상피성장인자 ...
"Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis". Nature. 560 (7717): 192-197. doi:10.1038/s41586-018- ... 44 (4): 177-82. ISSN 0012-835X.. *^ a b Carvalho E, Teixeira R, Johnson W Jr (1981). "Cell Mediated Immunity in American ... 83 (3): 860-4. doi:10.1172/JCI113969. PMC 303759. PMID 2522103.. *^ a b Rai A, Chandreshwar P, Singh A, et al. (2012). " ... 91 (4): 1664-8. doi:10.1172/JCI116372. PMC 288142. PMID 8097208.. *^ Ghalib H, Piuvezam M, Skeiky Y, et al. (1993). " ...
... cyclin-dependent kinase and DREAM complex. When it is time for a cell to enter S phase, complexes of cyclin-dependent kinases ( ... cyclin E and cyclin A), which push the cell through the cell cycle by activating cyclin-dependent kinases, and a molecule ... One such example of E2F-regulated genes repressed by Rb are cyclin E and cyclin A. Both of these cyclins are able to bind to ... Assembly of DREAM requires DYRK1A (Ser/Thr kinase) dependant phosphorylation of the MuvB core component, Lin52 at Serine28. ...
... and the cyclin dependent kinase inhibitors P27 and P21". Leuk. Lymphoma 43 (1): 51-7. PMID 11908736. doi:10.1080/10428190210195 ... "Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation". J. ... Invest. 26 (4): 459-72. PMID 9246566. doi:10.3109/08820139709022702.. *↑ 10,0 10,1 Wahl SM, Wen J, Moutsopoulos N (2006). "TGF- ... "Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis". Proc ...
사이클린이 특정 농도 이상이 되면 사이클린 의존성 키나아제(Cyclin-dependent Kinase, Cdk)와 결합하여 사이클린-Cdk 복합체를 만든다. Cdk는 여러 종류가 있으며 각각 Cdk-1, Cdk-2 와 같은 ... 유사 분열 과정에 오류가 생기면 두 개의 딸세포 대신 네 개의 딸세포가 되는 다중 분열이 이루어 질 수도 있다.[3] 이 외에도 세포자멸이나 돌연변이에 의해 무한히 분열 과정이 반복되는 암과 같은 오류가 있다.[4] ... 적혈구와 같은 세포는 세포 생존 기간이 4개월 정도로 짧기 때문에 조혈모세포에서는 유사 분열을 통해 계속하여 새로운 적혈구를 생성한다. 생식 세포를 만드는 감수 분열은 유사 분열의 특수한 경우이다. ... Molecular Cell Biology》 4판. W. H. Freeman. 2006년 1월 22일에 확인함.. ...
... and the cyclin dependent kinase inhibitors P27 and P21.». Leuk. Lymphoma 43 (1): 51-7. PMID 11908736. doi:10.1080/ ... de 2000). «Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of ... Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation». J ... 4]​ Posteriormente, fue caracterizado como un precursor proteico de gran tamaño (de unos 390 aminoácidos) que era procesado por ...
They inhibit all of the kinase-dependent functions of mTORC1 and mTORC2 and therefore, block the feedback activation of PI3K/ ... Rapamycin induces dephosphorylation of 4EBP1 as well, resulting in an increase in p27 and a decrease in cyclin D1 expression. ... protein tyrosine kinases and protein serine/threonine kinases. Dual-specificity kinases are subclass of the tyrosine kinases.[8 ... mTOR is a kinase within the family of phosphatidylinositol-3 kinase-related kinases (PIKKs),[9] which is a family of serine/ ...
cyclin binding. • cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine ... CDKN1A, CAP20, CDKN1, CIP1, MDA-6, P21, SDI1, WAF1, p21CIP1, cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase ... also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) ... 1994). "p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest ...
protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. Sci. U.S. ... cyclin binding. • cyclin-dependent protein serine/threonine kinase activity. • macromolecular complex binding. ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ...
regulation of cyclin-dependent protein serine/threonine kinase activity. • regulation of cellular component size. • response to ... negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell ... negative regulation of cyclin-dependent protein serine/threonine kinase activity. • negative regulation of neuron projection ... protein kinase B signaling. • cardiac muscle tissue development. • أيض الليبيدات. • شيخوخة. • neuron-neuron synaptic ...
MAPKs belong to the CMGC (CDK/MAPK/GSK3/CLK) kinase group. The closest relatives of MAPKs are the cyclin-dependent kinases ( ... MAP kinase kinase kinase (MAP3K or MKKK). *MAP kinase kinase kinases *MAP3K1 ... the cyclin-dependent kinases (CDKs), where substrates are recognized by the cyclin subunit, MAPKs associate with their ... A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine ...
Takahashi-Yanaga F, Sasaguri T (Apr 2008). "GSK-3beta regulates cyclin D1 expression: a new target for chemotherapy". Cellular ... "CD97 antibody depletes granulocytes in mice under conditions of acute inflammation via a Fc receptor-dependent mechanism". ... lateral cell-cell contacts and regulates the localization and degradation of β-catenin through glycogen synthase kinase-3β (GSK ... doi:10.1016/S0002-9440(10)64443-4. PMC 1850798. PMID 12414513.. *^ a b c Mustafa T, Eckert A, Klonisch T, Kehlen A, Maurer P, ...
These transitions are controlled by the cyclin-dependent kinase Cdk1.[10] 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. ...
cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4). 0.026. Ugt2a3. UDP glucuronosyltransferase 2 family, polypeptide A3 ... hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 4. 0.106. ...
... kinase/Akt pathway Cerebral organoids model human brain development and microcephaly IRF4 transcription factor-dependent CD11b+ ... CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary Predictors ... and the kinase RIP3 are key mediators of AAG-dependent alkylation-induced retinal degeneration Species-specific maturation ... hydrogels by human amniotic fluid-derived stem cells CDK1 substitutes for mTOR kinase to activate mitotic cap-dependent protein ...
Cyclin-Dependent Kinase Inhibitor p16 - genetics , Germ-Line Mutation , Carcinoma - genetics , Pancreatic Neoplasms - genetics ... 4. Full Text Family-based association of FKBP5 in bipolar disorder by Willour, V.L and Chen, H and Toolan, Jennifer and ... a bacterium with disulfide dependent infection and development ... Government Document (4) 4 Filter by. Remove filter. Reference ( ...
... stress-activated kinase signaling cascades, and PPAR signaling (most likely PPARγ). This latter effect may provide a ... Cyclin-dependent kinase (CDK) 5 (A) and Insulin-like growth factor (IGF)-1 signaling pathways (B) among 2,102 differentially ... Cheung ZH, Ip NY: The roles of cyclin-dependent kinase 5 in dendrite and synapse development. Biotechnol J. 2007, 2: 949-957. ... Pareek TK, Keller J, Kesavapany S, Pant HC, Iadarola MJ, Brady RO, Kulkarni AB: Cyclin-dependent kinase 5 activity regulates ...
Analysis of Cdk2 kinase activity and p27 binding to cyclin E complexes in the presence of exogenous wild-type p27 or p27T187A ... the release of galectin-9 was suppressed in a dose-dependent manner. ... The recombinant protein SjPP has been expressed in insect TN5B1-4 cells with proper antigenicity. The full-threshold and ...
Cyclin-Dependent Protein Kinase *Cytokines *DAPK *Deoxycytidine Kinase *DNA Topoisomerase *DNA-PK ... which is expressed on NK cells and dependent cellular cytotoxicity ADCC). It also participates in cytokine and superoxide ... Mouse monoclonal to Cyclin E2 NBCCS NSC-280594 Pik3r1 PKI-402 Plxnc1 Prp2 PU-H71 Rabbit Polyclonal to 5-HT-6 Rabbit polyclonal ... A more effective chemotherapy regimen including etoposide and ifosfamide was launched in 2003 [2,4]. Although ESFT are ...
The cyclin-dependent kinases (CDKs) have been intensely studied because of their involvement in regulating essential cellular ... We investigated whether there was a correlation between SNP genotypes in the IL-4 promoter and heart failure, and rejection ... Furthermore, pronex reviews similarities in IL-4 and IL-13 signal transduction have been also described, thus explaining the ... NADPH oxidase 4 mediates monocyte priming and accelerated chemotaxis induced by metabolic stress. ...
Ishida, Induction of the cyclin-dependent kinase inhibitor p21(Sdi1/Cip1/Waf1) by nitric oxide-generating vasodilator in ... Lee, NF-kappaB-dependent expression of nitric oxide synthase is required for membrane fusion of chick embryonic myoblasts. 1997 ... 4. NOS inhibitors increase cell proliferation in the optic tectum. Animals were treated with Elvax impregnated with the NOS ... 4). The histograms on theright depict quantitative changes induced by NOS inhibitors, which are presented in more detail in ...
Cyclic Nucleotide Dependent-Protein Kinase *Cyclin-Dependent Protein Kinase *Cyclooxygenase *CYP *CysLT1 Receptors ... exogenous cholesterol in a dose dependent style. November 22, 2019. By cancercurehere with Comments Off on Supplementary ... It had been noticed that rDer p 2 weakly bound to liposomes in a dosage dependent style (Fig.?1, best panel, Supplementary Fig ... Intro Pantothenate kinase-associated neurodegeneration (PKAN) may be the primary disorder of the nosological family members ...
A mathematical model for the interactions of cdc2 and cyclin is constructed. … Simulation and analysis of the model show that ... The transcript catalogue of the short-lived fish Nothobranchius furzeri provides insights into age-dependent changes of mRNA ... Cofactors ATP and NADPH were regenerated via pyruvate kinase and glucose dehydrogenase. A mathematical model was constructed on ... The proteins cdc2 and cyclin form a heterodimer (maturation promoting factor) that controls the major events of the cell cycle ...
... as well as upon deactivation of the mitogen-dependent MEK-Erk pathway or EGFR signaling. Reduction of RUNX2 levels by RNAi has ... kinase and phospholipase C-dependent mechanism. Cancer Res. 1999, 59: 5475-5478. ... Shen R, Wang X, Drissi H, Liu F, OKeefe RJ, Chen D: Cyclin d1-Cdk4 induce Runx2 ubiquitination and degradation. J Biol Chem. ... The phosphoinositide 3-kinase (PI3K) inhibitor Wortmannin has no effects on RUNX2 levels. MDA-MB-231 cells were incubated in ...
cyclin-dependent kinase inhibitor 1A. 0.016. flj13639. flj13639. 0.016. zgc:136826. zgc:136826. 0.016. ... SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4. 0.012. ...
... and cyclin E-associated kinase activities in the absence of significant changes in the amounts of cyclin-cdk complexes. Our ... Halothane and isoflurane inhibit endothelium-derived relaxing factor-dependent cyclic guanosine monophosphate accumulation in ... Loss of cyclin D can cause G(1) arrest in some cells, but in other cellular contexts, the downstream cyclin E protein can ... Cyclin D1 correlated with cytoplasmic c-myc expression and to a lesser extent with nuclear c-myc. ...
... phosphoinositide-dependent kinase, Akt/protein kinase B serine/threonine kinase, and G-proteins (e.g., Rac-GTPase). The FOXO ... FoxO3a and BCR-ABL regulate cyclin D2 transcription through a STAT5/BCL6-dependent mechanism. Mol Cell Biol 2004;24:10058-71. ... Dose-dependent induction of ABCB1 by FOXO3a:ER was also confirmed in the KD30 cell line (Fig. 5D). To investigate if FOXO3a ... Control of cell cycle exit and entry by protein kinase B-regulated forkhead transcription factors. Mol Cell Biol 2002;22:2025- ...
p27(Kip1) Inhibits Cyclin D-Cyclin-Dependent Kinase 4 by two independent modes. Mol Cell Biol 2009;29:986-99. ... Cyclin-dependent kinase 4/6 activity is a critical determinant of pre-replication complex assembly. Oncogene 2008;27:7083-93. ... the gene encoding the endogenous cyclin dependent kinase 4/6 (CDK4/6) inhibitor p16INK4a (3-6). KRAS is a small GTPase that ... Uncoupling of Cyclin D1 and pRB expression in response to MEK inhibition is cell line dependent. Immunoblotting analyses ...
... which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the ... Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads ... Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and ... Protein kinase c activity. Specific Function:. Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/ ...
Importantly, anti-leptin treatment induced a failure to downmodulate the cyclin-dependent kinase inhibitor p27 (p27Kip-1) in ... Figure 4. In vivo leptin neutralization with mouse ObR:Fc chimera in SJL/J mice inhibits DTH response and induces T cell ...
... including the stimulation of the phosphatidylinositol 3-kinase/protein kinase B and the phospholipase C-gamma/Ras GDP-releasing ... cyclin, and CKI families. Combined clinical and US assessment identifies individuals in remission who may be suitable for anti- ... and concentration-dependent manner, as visualized by their failure to migrate into SDS gels. ... The tyrosine kinase inhibitor imatinib mesylate delays prion neuroinvasion by inhibiting prion propagation in the periphery. ...
We underlined also that gene expression of CDKN1A (cyclin-dependent kinase inhibitor 1A) and CDKN2A (cyclin-dependent kinase ... Figure 4) By focusing on the intermediary condition of repetitive UVB (75 mJ/cm²) + UVA (7 J/cm²) exposure, we highlighted an ... NHDF were cultured and irradiated with 15 J/cm² UVA once a day, for 4 days, obtaining NHDFuv, and maintained in culture for ... RecSkin built with NHDF was submitted to UVA+B irradiations at different doses, once a day, for 4 days: RecSkinUV. (Figure 1) ...
Aurora Kinase. *Cdc2-like Kinase (CLK). *Checkpoint Kinase (Chk). *Cyclin-dependent Kinase (CDK) ... 1-[(3S)-3-{4-amino-3-[(3,5-dimethoxyphenyl)ethynyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl}pyrrolidin-1-yl]prop-2-en1-one. ... 2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO. ... 对野生型 FGFR1/2/3/4 以及某些 FGFR2 激酶结构域突变表现
... through suppression of the cyclin-dependent kinase inhibitor p27, increases their proliferative as well as their metastatic ... miR-34a and miR-34b/c expression can be induced by DNA damage and oncogenic stress in a p53-dependent manner. The introduction ... Recent evidences have demonstrated that let-7a acts as a tumor-suppressor in prostate cancer by downregulating E2F2 and cyclin ... dependent MYCN inhibition. On the other end, miR-34a indirectly controls p53 activation through SIRT1. Inhibition of SIRT1 by ...
Bcr-Abl kinase down-regulates cyclin-dependent kinase inhibitor p27 in human and murine cell lines. Blood 2000;96:1933-9. ... BCR/ABL oncogenic kinase promotes unfaithful repair of the reactive oxygen species-dependent DNA double-strand breaks. Blood ... Fusion tyrosine kinases induce drug resistance by stimulation of homology-dependent recombination repair, prolongation of G(2)/ ... Bcr-Abl kinase promotes cell cycle entry of primary myeloid CML cells in the absence of growth factors. Br J Haematol 1998;100: ...
deletion (del)(9p) (cyclin-dependent kinase inhibitor 2A [CDKN2A]/Cen9), and t(14;var). (immunoglobulin heavy chain [IGH] is ... diagnosed breakpoint cluster region (BCR)-c-abl oncogene 1, non-receptor tyrosine kinase. (ABL)-negative B lineage acute ... or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO on days 1-14,. 29-42, pegaspargase IM or IV on ... INTENSIFICATION THERAPY: Beginning 4 weeks after the completion of course 2 of induction. therapy, patients receive ...
Study Shows New Class of Proteins Allows Breast Cancer Cells to Evade Tyrosine Kinase Inhibitors Advances in Cartilage Tissue ... Vertebrate Evolution Four New Genetic Diseases Defined Within Schizophrenia Age-Dependent Changes in Pancreatic Function ... iPS Cells to Reverse Blindness Picking Cancer Stems Cell Out of the Crowd Scientists Identify Surprising Function for Cyclin D1 ... Disease Chemists Create Microscopic Environment to Study Cancer Cell Growth Systems-based analysis of RIG-I-dependent ...
cyclin-dependent kinase 5 regulatory subunit 1. protein-coding. LOC688126. hypothetical protein LOC688126. protein-coding. ...
  • [4] Stable association encourages MCM helicase to unwind a small stretch of parental DNA into two strands of ssDNA, which in turn recruits replication protein A ( RPA ), an ssDNA binding protein. (popflock.com)
  • Cyclin D1 and CDK4/6 are downstream of signaling pathways that induce cellular proliferation. (ascopost.com)
  • Our results indicated that cyclin A, cyclin D, Cdk2, Cdk4, and p21 are involved in microglial proliferation in the transected facial nucleus, and that the M-CSF-dependent upregulations of cyclins/PCNA and cFms in microglia are differentially regulated by JNK and p38. (termsreign.tk)
  • Mitogenic signals received throughout G1-phase cause gradual accumulation of cyclin D, which complexes with CDK4/6. (popflock.com)
  • Active cyclin D-CDK4/6 complex induces release of E2F transcription factor, which in turn initiates expression of S-phase genes. (popflock.com)
  • context" : "http://schema.org", "@type" : "Product", "name" : " Human CDK4 (Cyclin Dependent Kinase 4) CLIA Kit (HUES01201)", "image" : "https://www.elisagenie.com/product_images/t/571/SC-E-CL-H1356__31641.jpg", "description" : "Human CDK4. (elisagenie.com)
  • Cell cycle markers cyclin D, Cdk4, and Ki67 are found in elevated levels in AD neurons, signifying the transition to G1 (McShea et al. (wikipedia.org)
  • alkB homolog 4, lysine demethylase [S. (gsea-msigdb.org)
  • We used the UC1 strain to study cleistothecia formation by searching for differences between UC1 and its parent G217B, and we determined that the H. capsulatum homolog of protein kinase C (PKC1) plays a role in cleistothecia formation. (checkpointsignaling.com)
  • Wingless signaling was discovered to be regulated by zeste-white 3 (also called Shaggy), which is the Drosophila ''' homolog ''' of mammalian Glycogen Synthase Kinase-3 (GSK-3). (edu.au)
  • Thus there is constitutive as well as inducible suppression of ERKs and c-jun NH2-terminal protein kinases by MKP and PP-2A/PP-1 in the adult cardiac myocyte phenotype. (storysteel.gq)
  • Pathway enrichment analysis indicated that HCV induced an increased expression of genes involved in mitogen-activated protein kinases signaling, adipocytokine signaling, cell cycle and nitrogen metabolism. (edu.pl)
  • We find that, similar to its regulation in osteoblasts, RUNX2 expression in MDA-MB-231 breast adenocarcinoma cells is enhanced upon growth factor deprivation, as well as upon deactivation of the mitogen-dependent MEK-Erk pathway or EGFR signaling. (biomedcentral.com)
  • The phosphoinositide 3-kinase (PI3K)/Akt pathway is frequently implicated in tumorigenesis and chemotherapeutic resistance ( 7 , 8 ). (aacrjournals.org)
  • Additional evidence highlights that miR-15a and miR-16-1 might control other genes involved in the programmed cell death pathway and cell cycle checkpoints such as CCND1 (encoding cyclin D1) and WNT3A, promoting several tumorigenic features, including survival, proliferation, and invasion. (arraystar.com)
  • There is also evidence in S. cerevisiae for a functional link between the pheromone response MAP kinase pathway and the MAP kinase pathway involved in cell wall integrity, as S. cerevisiae strains lacking the MAP kinase Slt2 die after exposure to pheromone . (checkpointsignaling.com)
  • A contribution on the pathogenesis of hemorrhagic diathesis in acute promyelocytic leukemia The results suggest that in vertebrates at the interface between cells in the floorplate and in the paraxial neuroectoderm, at the limited region of the mid/hindbrain border, En-1 interacts with wnt-1 in a signaling pathway analogous to the engrailed/wingless signaling in the parasegments of the Drosophila embryo. (termsreign.ga)
  • context" : "http://schema.org", "@type" : "Product", "name" : " Human CCND2 / Cyclin D2 ELISA Kit", "image" : "https://www.elisagenie.com/product_images/i/191/EH2777__44314.jpg", "description" : "Human CCND2/Cyclin D2 ELISA Kit assay has a. (elisagenie.com)
  • 16. Millband DN, Hardwick KG (2002) Fission yeast Mad3p is required for Mad2p to inhibit the anaphase-promoting complex and localizes to kinetochores in a Bub1p-, Bub3p-, and Mph1p-dependent manner. (aimspress.com)
  • In the present study, reverse transcription (RT)-PCR and western blot analysis revealed that OX1R mRNA expression and activation in rat hepatocytes in vitro were upregulated by exogenous orexin A (10-10 to 10-6 M) in a dose-dependent manner. (spandidos-publications.com)
  • PI3Ks are a family of lipid kinases that serve as mediators of signals generated by many different activated growth factor receptors and adhesion molecules. (aacrjournals.org)
  • Expression of a PSKH1 mutant where the COOH-terminal kinase domain was swapped with green fluorescent protein and cysteine 3 was exchanged with serine resulted in disassembly of the Golgi apparatus as visualized by redistribution of beta-COP and GM130 to a diffuse cytoplasmic pattern, while leaving the tubulin skeleton intact. (storysteel.gq)
  • For grade 3 neutropenia with fever/infection and for grade 4 events, palbociclib should be withheld until recovery to grade ≤ 2 and restarted at the next lower dose. (ascopost.com)
  • Substrate specificity of the cdk-activating kinase (CAK) is altered upon association with TFIIH. (hawaiilibrary.net)
  • Enhancement of ABL kinase catalytic efficiency by a direct binding regulator is independent of other regulatory mechanisms. (mousemine.org)
  • miR-34a and miR-34b/c expression can be induced by DNA damage and oncogenic stress in a p53-dependent manner. (arraystar.com)
  • Normal ABL1 is a tumor suppressor and therapeutic target in human and mouse leukemias expressing oncogenic ABL1 kinases. (mousemine.org)
  • Antigen standard for cyclin Y (CCNY), transcript variant 2 is a lysate prepared from HEK293T cells transiently transfected with a TrueORF gene-carrying pCMV plasmid and then lysed in RIPA Buffer. (creativebiomart.net)
  • We found that NVD induced cytotoxicity in colorectal cells in a dose-dependent manner and time dependent approach. (biomedcentral.com)
  • The effect of low doses of radiation on central organs of erythro- and lymphocytopoiesis in the human fetus These transfectants showed a significant reduction in cell motility with exogenous nm23-H1 in a dose-dependent manner, and exhibited a noninvasive character. (termsreign.ga)
  • Patient 3 has a novel mutation ABCC8/F1182S and Patient 4 has a paternal duplication on chromosome 6q24. (storysteel.gq)
  • S100A8 and S100A9 activate MAP kinase and NF-kappaB signaling pathways and trigger translocation of RAGE in human prostate cancer cells. (termsreign.gq)
  • 2006. Compartmental distribution of hyperpolarization-activated cyclic-nucleotide-gated channel 2 and hyperpolarization-activated cyclic-nucleotide-gated channel 4 in thalamic reticular and thalamocortical relay neurons. . (cornell.edu)
  • Clinico-hormonal characteristics of retarded development of the female sexual system of central origin The specificity of cRac1B action observed in neurons was not observed in fibroblasts, where both GTPases produced similar effects on cell morphology and actin organization, indicating the existence of a cell type-dependent specificity of cRac1B function. (storysteel.gq)
  • 4. Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the 1st line therapy. (mycancergenome.org)
  • PPARγ was first identified in 1992 in Xenopus [ 4 ] and then in 1993 in mice [ 5 ]. (mdpi.com)
  • This is an open-label, randomized, multicenter Phase 3 study to compare the efficacy and safety of Sacituzumab Govitecan versus TPC in subjects with metastatic or locally recurrent inoperable HR+/HER2- MBC, after failure of at least 2, and no more than 4, prior chemotherapy regimens for metastatic disease. (mycancergenome.org)
  • Tumors from PI-103-treated mice shows higher levels of cyclin D1 and more proliferating cells . (medchemexpress.com)
  • The intravenous Se injection of 4.06107 results Jeko-1 cells in a tumor spread after 3 and 4 weeks after injection, without surgery are the Mice, a median survival time of 28 days. (micrornaassay.com)
  • We further propose a mechanism linking LRRK2 dimerisation, GTPase function and membrane recruitment with LRRK2 kinase activation by Rab29. (biomedcentral.com)
  • dephospho-CoA kinase domain containing. (gsea-msigdb.org)
  • PPARs have modular structures containing a N-terminal A/B region with a transactivation domain (AF1), a DNA binding domain (DBD) with two zinc-finger motifs and a C-terminal ligand-binding domain (LBD) with the ligand-dependent transactivation function (AF2) [ 2 , 3 ]. (mdpi.com)
  • It also affects the nervous system by inhibiting protein kinase C and alkaline phosphatase, which impairs brain microvascular formation and function, as well as alters the blood-brain barrier. (t3db.ca)
  • Since the discovery of leucine-rich repeat kinase 2 (LRRK2) as a protein that is likely central to the aetiology of Parkinson's disease, a considerable amount of work has gone into uncovering its basic cellular function. (biomedcentral.com)