Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.Cyclin-Dependent Kinase Inhibitor 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 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.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.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-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.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.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.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.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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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.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.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.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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.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.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 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.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 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.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-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 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.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 D3: A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.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.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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.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.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.Cyclin-Dependent Kinase Inhibitor p18: An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN-LIKE REPEATS. Aberrant expression of this protein has been associated with deregulated EPITHELIAL CELL growth, organ enlargement, and a variety of NEOPLASMS.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.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.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.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.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.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.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.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.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 A1: A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.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.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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 G: A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.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.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.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.Cyclin-Dependent Kinase Inhibitor p15: An INK4 cyclin-dependent kinase inhibitor containing four ANKYRIN-LIKE REPEATS. INK4B is often inactivated by deletions, mutations, or hypermethylation in HEMATOLOGIC NEOPLASMS.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.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.Cyclin A2: A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.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.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.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.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.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.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)Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Cyclin-Dependent Kinase Inhibitor p19: An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN REPEATS. Aberrant expression of this protein has been associated with TESTICULAR CANCER.S-Phase Kinase-Associated Proteins: A family of structurally-related proteins that were originally identified by their ability to complex with cyclin proteins (CYCLINS). They share a common domain that binds specifically to F-BOX MOTIFS. They take part in SKP CULLIN F-BOX PROTEIN LIGASES, where they can bind to a variety of F-BOX PROTEINS.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.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.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.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.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.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.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.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.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.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.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.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).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.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.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.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.Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.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.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)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.Proto-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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.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.Benzamides: BENZOIC ACID amides.Kinetics: The rate dynamics in chemical or physical systems.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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Mice, Inbred C57BLChromones

Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis. (1/4670)

The cyclin-dependent kinase inhibitor p21waf1/Cip1 is a downstream effector of the p53-dependent cell growth arrest. We report herein that p21 was cleaved by caspase-3/CPP32 at the site of DHVD112L during the DNA damage-induced apoptosis of cancer cells. The cleaved p21 fragment could no more arrest the cells in G1 phase nor suppress the cells undergoing apoptosis because it failed to bind to the proliferating cell nuclear antigen (PCNA) and lost its capability to localize in the nucleus. Thus, caspase-3-mediated cleavage and inactivation of p21 protein may convert cancer cells from growth arrest to undergoing apoptosis, leading to the acceleration of chemotherapy-induced apoptotic process in cancer cells.  (+info)

Caspase 3 inactivation to suppress Fas-mediated apoptosis: identification of binding domain with p21 and ILP and inactivation machinery by p21. (2/4670)

The death mediator caspase acts as the dominant regulator during cell death induction. The CPP32 subfamily, including caspase 3 (CPP32/Yama/Apopain), is essential for the cell death signaling. We recently reported that activation of caspase 3 is regulated by complex formation with p21 or ILP. In the present study, we investigated the binding domain with p21 and ILP to further characterize the caspase 3 inactivation machinery. Our results show that caspase 3 contains p21 binding domain in the N-terminus and ILP binding domain in the active site. Further, the caspase 3 binding domain in p21 was independent of the Cdk- or PCNA-binding domain. We also found caspase 3 protection by p21 from the p3-site cleavage serineproteinase contributes to the suppression machinery. Here, we propose the caspase 3 inactivation system by p21 and ILP as new essential system in the regulation of cell death.  (+info)

Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. (3/4670)

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)

Cell growth inhibition by farnesyltransferase inhibitors is mediated by gain of geranylgeranylated RhoB. (4/4670)

Recent results have shown that the ability of farnesyltransferase inhibitors (FTIs) to inhibit malignant cell transformation and Ras prenylation can be separated. We proposed previously that farnesylated Rho proteins are important targets for alternation by FTIs, based on studies of RhoB (the FTI-Rho hypothesis). Cells treated with FTIs exhibit a loss of farnesylated RhoB but a gain of geranylgeranylated RhoB (RhoB-GG), which is associated with loss of growth-promoting activity. In this study, we tested whether the gain of RhoB-GG elicited by FTI treatment was sufficient to mediate FTI-induced cell growth inhibition. In support of this hypothesis, when expressed in Ras-transformed cells RhoB-GG induced phenotypic reversion, cell growth inhibition, and activation of the cell cycle kinase inhibitor p21WAF1. RhoB-GG did not affect the phenotype or growth of normal cells. These effects were similar to FTI treatment insofar as they were all induced in transformed cells but not in normal cells. RhoB-GG did not promote anoikis of Ras-transformed cells, implying that this response to FTIs involves loss-of-function effects. Our findings corroborate the FTI-Rho hypothesis and demonstrate that gain-of-function effects on Rho are part of the drug mechanism. Gain of RhoB-GG may explain how FTIs inhibit the growth of human tumor cells that lack Ras mutations.  (+info)

Induced expression of p16(INK4a) inhibits both CDK4- and CDK2-associated kinase activity by reassortment of cyclin-CDK-inhibitor complexes. (5/4670)

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. (6/4670)

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)

Functions of cyclin A1 in the cell cycle and its interactions with transcription factor E2F-1 and the Rb family of proteins. (7/4670)

Human cyclin A1, a newly discovered cyclin, is expressed in testis and is thought to function in the meiotic cell cycle. Here, we show that the expression of human cyclin A1 and cyclin A1-associated kinase activities was regulated during the mitotic cell cycle. In the osteosarcoma cell line MG63, cyclin A1 mRNA and protein were present at very low levels in cells at the G0 phase. They increased during the progression of the cell cycle and reached the highest levels in the S and G2/M phases. Furthermore, the cyclin A1-associated histone H1 kinase activity peaked at the G2/M phase. We report that cyclin A1 could bind to important cell cycle regulators: the Rb family of proteins, the transcription factor E2F-1, and the p21 family of proteins. The in vitro interaction of cyclin A1 with E2F-1 was greatly enhanced when cyclin A1 was complexed with CDK2. Associations of cyclin A1 with Rb and E2F-1 were observed in vivo in several cell lines. When cyclin A1 was coexpressed with CDK2 in sf9 insect cells, the CDK2-cyclin A1 complex had kinase activities for histone H1, E2F-1, and the Rb family of proteins. Our results suggest that the Rb family of proteins and E2F-1 may be important targets for phosphorylation by the cyclin A1-associated kinase. Cyclin A1 may function in the mitotic cell cycle in certain cells.  (+info)

Immunohistochemical expression of mdm2 and p21WAF1 in invasive cervical cancer: correlation with p53 protein and high risk HPV infection. (8/4670)

AIM: To investigate the immunocytochemical staining pattern of mdm2 and p21WAF1 proteins in invasive cervical cancer and to determine its relation with the expression of p53 and with the high risk HPV infection. METHODS: Immunocytochemistry for p53, mdm2, and p21WAF1 was performed in 31 paraffin embedded sections of invasive cervical cancer. The results were assessed by image analysis, evaluating for each protein the optical density of the immunostained area, scored as percentage of the total nuclear area. The presence of high risk human papillomavirus (HPV) infection was detected by using the polymerase chain reaction. RESULTS: Immunostaining for both mdm2 and p21WAF1 was correlated with p53 expression; however, the correlation between p53 and mdm2 (R = 0.49; p < 0.01) was more significant than between p53 and p21WAF1 (R = 0.31; p < 0.05); the less stringent correlation between p53 and p21WAF1 might reflect the p53 independent mechanisms of p21WAF1 induction. Similar average levels of p53, mdm2, and p21WAF1 immunostaining were found in the presence or absence of high risk HPV-DNA, without significant differences between the two groups. CONCLUSIONS: These data suggest that mdm2 and p21WAF1 proteins are expressed in invasive cervical cancer and that their immunocytochemical staining pattern is not abrogated by the presence of high risk HPV genomic sequences.  (+info)

*DNA repair

The cyclin-dependent kinase inhibitor p21 is induced by both p53-dependent and p53-independent mechanisms and can arrest the ... ISBN 1-58829-500-1. [page needed] Gartel AL, Tyner AL (June 2002). "The role of the cyclin-dependent kinase inhibitor p21 in ... cell cycle at the G1/S and G2/M checkpoints by deactivating cyclin/cyclin-dependent kinase complexes. The SOS response is the ... In one of the earliest steps, the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), phosphorylates SIRT6 on ...

*P21

... also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) ... p21 is a potent cyclin-dependent kinase inhibitor (CKI). The p21 (CIP1/WAF1) protein binds to and inhibits the activity of ... CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1)". Gartel AL, Radhakrishnan SK (May 2005). "Lost in transcription: p21 ... Cyclin-Dependent Kinase Inhibitor p21 at the US National Library of Medicine Medical Subject Headings (MeSH) Drosophila dacapo ...

*TBX2

... cyclin-dependent kinase inhibitor". Cancer Research. 64 (5): 1669-74. PMID 14996726. Rodriguez M, Aladowicz E, Lanfrancone L, ... Prince S, Carreira S, Vance KW, Abrahams A, Goding CR (March 2004). "Tbx2 directly represses the expression of the p21(WAF1) ... It is known that Tbx2 functions in a dose-dependent manner; therefore, duplication or deletion of the region encompassing Tbx2 ... "T-box 2 represses NDRG1 through an EGR1-dependent mechanism to drive the proliferation of breast cancer cells". Oncogene. 29 ( ...

*CDKN1B

... and the cyclin dependent kinase inhibitors P27 and P21". Leuk. Lymphoma. 43 (1): 51-7. doi:10.1080/10428190210195. PMID ... CDKN1B has been shown to interact with: AKT1, CKS1B, Cyclin D3, Cyclin E1, Cyclin-dependent kinase 2, Cyclin-dependent kinase 4 ... Cyclin-dependent kinase inhibitor 1B (p27Kip1) is an enzyme inhibitor that in humans is encoded by the CDKN1B gene. It encodes ... vitamin D receptor and cyclin-dependent kinase inhibitors, p21 and p27". Nephrol. Dial. Transplant. 18 Suppl 3: iii9-12. doi: ...

*Epigenetic regulation of neurogenesis

This includes the cyclin-dependent kinase inhibitor P21 and the tumor suppressor gene Pten to promote neural stem cell ... HDAC inhibitors exhibited positive effects on mice with cognitive defects such as Alzheimers disease and improved the cognition ... DNA demethylation, as well as methylation, of certain genes allows for neurogenesis to proceed in a time dependent manner. One ... It entails many different complex processes which are all time and order dependent. Processes such as neuron proliferation, ...

*K562 cells

This gene targets the cyclin-dependent kinase inhibitor, p21, and causes cell differentiation, cell cycle arrest in G1, and ... The problem with K562 cells, and many other cancer cell types, is an overabundance of Aurora kinases. These kinases play a role ... However, the overabundance of Aurora kinases allows for uncontrolled cellular division, resulting in cancer. Inhibiting these ...

*Myosatellite cell

Increased levels of myostatin up-regulate a cyclin-dependent kinase inhibitor called p21 and thereby inhibit the ... and p21 mRNA levels. This is consistent with the fact that cyclin D1 and p21 upregulation correlates to division and ... Relaix F, Rocancourt D, Mansouri A, Buckingham M (2005). "A Pax3/Pax7-dependent population of skeletal muscle progenitor cells ... Notably, HGF, a cytokine, is transferred from the extracellular matrix into muscles through the nitric-oxide dependent pathway ...

*TGF beta 1

... and the cyclin dependent kinase inhibitors P27 and P21". Leuk. Lymphoma. 43 (1): 51-7. doi:10.1080/10428190210195. PMID ... Interleukin 1- and interleukin 2-dependent proliferation of activated T cells, and the activation of quiescent helper T cells ... "Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis". Proc. ... "Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation". J. ...

*RHOA

... primarily through regulation of cyclin D1 and cyclin-dependent kinase inhibitors (p21 and p27) expression. These regulation ... Leung T, Chen XQ, Manser E, Lim L (October 1996). "The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is ... RhoA activates ROCK (RhoA kinase) which stimulates LIM kinase, which then stimulates cofilin, which effectively reorganizes the ... Due to pathophysiological overlap of RhoA and Rho-kinase in asthma, both RhoA and Rho-kinase have become promising new target ...

*Arsenic biochemistry

Inhibition in MC/CAR Myeloma Cells via Cell Cycle Arrest in Association with Induction of Cyclin-dependent Kinase Inhibitor, ... p21, and Apoptosis". Cancer Research. 60 (3065): 3065-71. PMID 10850458. Retrieved 2010-12-15. "Arsenic in Drinking Water - ... The inositol-requiring enzyme-1 (IRE1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) are two receptors that ... Sykora, P; Snow, E.T (2008). "Modulation of DNA polymerase beta-dependent base excision repair in cultured human cells after ...

*Wafik El-Deiry

"The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases". Cell. 75 (4): 805-816. ISSN 0092- ... "p21 is a universal inhibitor of cyclin kinases". Nature. 366 (6456): 701-704. doi:10.1038/366701a0. ISSN 1476-4687. Noda, Asao ... Yue Xiong and David Beach as a cyclin-CDK-PCNA interacting protein (p21), and as a senescence derived inhibitor by Noda. ... p21(WAF1) was the first mammalian cell cycle inhibitor to be discovered, and was found independently by Wade Harper and Steve ...

*HIST1H1B

"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... Marzluff WF, Gongidi P, Woods KR, Jin J, Maltais LJ (Oct 2002). "The human and mouse replication-dependent histone genes". ... 1999). "Cloning and characterization of RLPK, a novel RSK-related protein kinase". J. Biol. Chem. 274 (2): 1026-32. doi:10.1074 ... the CDK-activating kinase". J. Biol. Chem. 270 (31): 18195-7. doi:10.1074/jbc.270.31.18195. PMID 7629134. Albig W, Drabent B, ...

*Flap structure-specific endonuclease 1

... and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21". J. Biol. Chem. ... and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21". J. Biol. Chem. ... Henneke G, Koundrioukoff S, Hübscher U (Jul 2003). "Phosphorylation of human Fen1 by cyclin-dependent kinase modulates its role ... FEN1 is an essential enzyme in an inaccurate pathway for repair of double-strand breaks in DNA called microhomology-dependent ...

*Proliferating cell nuclear antigen

... and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21". J. Biol. Chem. ... Cyclin D1, Cyclin O, Cyclin-dependent kinase 4, Cyclin-dependent kinase inhibitor 1C, DNMT1, EP300, Flap structure-specific ... "A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor ... "Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell ...

*CDKN3

1993). "The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases". Cell. 75 (4): 805-16. doi: ... It was identified as a cyclin-dependent kinase inhibitor, and has been shown to interact with, and dephosphorylate CDK2 kinase ... "The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases". Cell. UNITED STATES. 75 (4): 805-16 ... Cyclin-dependent kinase inhibitor 3 is an enzyme that in humans is encoded by the CDKN3 gene. The protein encoded by this gene ...

*Bharat Aggarwal

... degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 ... In 1996, Aggarwal patented curcumin as an inhibitor of NF-κB activation, and he co-founded a company in 2004 called Curry ...

*CUL4B

... and degradation of replication licensing factor Cdt1 and cyclin-dependent kinase inhibitor p21 in a proteasome-dependent manner ... Nishitani H, Shiomi Y, Iida H, Michishita M, Takami T, Tsurimoto T (Oct 2008). "CDK inhibitor p21 is degraded by a ... Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A (Sep 2008). "PCNA-dependent regulation of p21 ubiquitylation and ... "Involvement of CUL4 ubiquitin E3 ligases in regulating CDK inhibitors Dacapo/p27Kip1 and cyclin E degradation". Cell Cycle. 5 ( ...

*CUL4A

... regulating protein expression levels of the replication licensing factor protein Cdt1 and cyclin-dependent kinase inhibitor p21 ... loss of Cdt2 expression also result in p21 dependent delayed S-phase entry, and re-expression of p21 in S-phase, which results ... Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A (Sep 2008). "PCNA-dependent regulation of p21 ubiquitylation and ... Nishitani H, Shiomi Y, Iida H, Michishita M, Takami T, Tsurimoto T (Oct 2008). "CDK inhibitor p21 is degraded by a ...

*Lovastatin

... leading to an accumulation of cyclin-dependent kinase inhibitors p21 and p27, and to subsequent G1-phase arrest, as seen in ... Lovastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), an enzyme that catalyzes the ... The first breakthrough in efforts to find a potent, specific, competitive inhibitor of HMG CoA reductase occurred in 1976, when ... Lovastatin was the first specific inhibitor of HMG CoA reductase to receive approval for the treatment of hypercholesterolemia ...

*GADD45G

GADD45 also works with the cyclin-dependent kinase inhibitor p21, which can cause growth arrest as well. GADD45G is found to be ... GADD45G prevents the kinase ability of the cyclin b1/Cdk1 complex in a fashion that does not break apart the complex. It plays ... Vairapandi M, Balliet AG, Hoffman B, Liebermann DA (2002). "GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role ... It also interacts with CRIF, which causes the inhibition of Cdc2-cyclin B1 and Cdk-cyclin E. ...

*Cyclin-dependent kinase 7

"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... Cyclin-dependent kinase 7 has been shown to interact with: Androgen receptor, Cyclin H, GTF2H1, MNAT1, P53, SUPT5H, and XPB. ... "Entrez Gene: CDK7 cyclin-dependent kinase 7 (MO15 homolog, Xenopus laevis, cdk-activating kinase)". Lee DK, Duan HO, Chang C ( ... Drapkin R, Le Roy G, Cho H, Akoulitchev S, Reinberg D (Jun 1996). "Human cyclin-dependent kinase-activating kinase exists in ...

*Cyclin-dependent kinase 6

"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein ... 2003). "Expression of Cyclin-Dependent Kinase 6, but Not Cyclin-Dependent Kinase 4, Alters Morphology of Cultured Mouse ... A Cyclin-dependent kinase 6 interacts with: CDKN2C, Cyclin D1, Cyclin D3, P16, PPM1B, and PPP2CA. Cell cycle, Mitosis, CDK, ...

*Histone acetylation and deacetylation

... embryogenesis and showed a drastic reduction in the production but increased expression of Cyclin-Dependent Kinase Inhibitors ( ... HDACs 1 and 2 have been found to express regulatory roles in key cell cycle genes including p21. Activity of these HDACs can be ... Binding of HDACs to MEF2 inhibits muscle differentiation, which can be reversed by action of Ca2+/calmodulin-dependent kinase ( ... Nucleosome formation is dependent on the positive charges of the H4 histones and the negative charge on the surface of H2A ...

*Cyclin-dependent kinase 2

"The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases". Cell. 75 (4): 805-16. doi:10.1016/ ... Cyclin-dependent kinase 2 has been shown to interact with: BRCA1, CDK2AP1, CDKN1B CDKN3, CEBPA, Cyclin A1, Cyclin E1, Flap ... Cyclin-dependent kinase 2, also known as cell division protein kinase 2, is an enzyme that in humans is encoded by the CDK2 ... The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein kinases. This protein ...

*CDKN2B

"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... Cyclin-dependent kinase 4 inhibitor B also known as multiple tumor suppressor 2 (MTS-2) or p15INK4b is a protein that is ... "Entrez Gene: CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)". Rual JF, Venkatesan K, Hao T, Hirozane- ... This gene encodes a cyclin-dependent kinase inhibitor, also known as p15Ink4b protein, which forms a complex with CDK4 or CDK6 ...

*Cell cycle

Two key classes of regulatory molecules, cyclins and cyclin-dependent kinases (CDKs), determine a cell's progress through the ... The G1 cyclin-CDK complexes also promote the degradation of molecules that function as S phase inhibitors by targeting them for ... They halt cell cycle in G1 phase, by binding to, and inactivating, cyclin-CDK complexes. p21 is activated by p53 (which, in ... cyclin A, DNA polymerase, thymidine kinase, etc. Cyclin E thus produced binds to CDK2, forming the cyclin E-CDK2 complex, which ...
(KudoZ) English to Bosnian translation of EURO parity CIP : (cijene...) u EUR na paritetu CIP... [Finance (general) (Bus/Financial)].
Chronic lymphocytic leukemia (CLL) cells multiply and become more resistant to immunochemotherapy in "proliferation centers" within tissues, whereas apoptosis occurs in the periphery. Various models recapitulate these microenvironments in vitro, such as stimulation with CD154 and IL4. Using this system, we observed a 30- to 40-fold induction of wild-type p53 protein in 50 distinct human CLL specimens tested, without the induction of either cell-cycle arrest or apoptosis. In contrast, the mRNA levels for p53 did not increase, indicating that its elevation occurred posttranscriptionally. Mechanistic investigations revealed that under the conditions studied, p53 was phosphorylated on residues associated with p53 activation and increased half-life. However, p53 protein induced in this manner could transcriptionally activate only a subset of target genes. The addition of a DNA-damaging agent further upregulated p53 protein levels, which led to apoptosis. p53 induction relied on the increase in ...
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.
Folia Histochemica et Cytobiologica (FHC) is an international,English-language journal devoted to the developing fields of histochemistry,cytochemistry,cell biology,cell and tissue biology.It is source of the recent research in fields of and cell biology
Harrison, T.A., Smith Adams, L.B., Moore, P.D., Perna, M.K., Sword, J.D.and Defoe, D. M.. Accelerated turnover of taste bud cells in mice deficient for the cyclin-dependent kinase inhibitor p27Kip1.BMC Neuroscience 2011, 12:34 ...
Results: In vitro studies showed a pronounced growth inhibitory and pro-apoptotic effect of LBH589 on both HCC cell lines at low micromolar concentrations (IC50 approx. 0.1 µM). Interstingly, the pro-apoptotic effect of Panobinostat was not paralleled by a breakdown of ΔΨm. p53wt HepG2 cells were more sensitive than the p53-/- Hep3B cells. Quantitative PCR and western blotting showed an involvement of the cell cycle regulators p21cip1/waf1 and Chek1 but not the bax/bcl-2 system. Panobinostat regulated the expression of p21cip1/waf1 via a transcriptional upregulation as evidenced by ChIP ...
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 ...
Due to its role in aging and antitumor defense, cellular senescence has recently attracted increasing interest. However, [the] detection of senescent cells remains difficult due to the lack of specific biomarkers. ndeed, most determinants of cellular senescence, such as the upregulation of p53, p16Ink4a, p21WAF/CIP1 or SASP-associated cytokines, are not exclusively observed in senescence, but can also occur in other types of stress responses. In addition, alterations like SAHF or DNA-SCARS formation are frequently observed, but not necessarily a mandatory feature or exclusive to senescent cells. The current gold standard for the detection of senescence is the so-called senescence-associated β-galactosidase (SA-β-Gal) activity. Although SA-β-Gal has been first suggested as a distinct enzyme, its activity is derived from lysosomal β-Gal encoded by the GLB1 gene. β-Gal is an accepted marker of senescence, but its reliability and specificity have been questioned, as a positive β-Gal reaction ...
1OIT: Imidazo[1,2-A]Pyridines: A Potent and Selective Class of Cyclin-Dependent Kinase Inhibitors Identified Through Structure-Based Hybridisation
Complete information for CDKN2B gene (Protein Coding), Cyclin Dependent Kinase Inhibitor 2B, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for CDKN2B gene (Protein Coding), Cyclin Dependent Kinase Inhibitor 2B, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
1E1X: Identification of Novel Purine and Pyrimidine Cyclin-Dependent Kinase Inhibitors with Distinct Molecular Interactions and Tumor Cell Growth Inhibition Profiles.
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The major findings in this study are that the Kip/Cip and Ink CKIs differentially regulate cdk2 and cdk4 in VSMCs; this, in turn, leads to differences in the inhibition of VSMC proliferation in vitro and in vivo. The expression of p27Kip1 and p21Cip1 in VSMCs inactivated cdk2 and cdk4, whereas p16Ink4 inhibited only cdk4 activity. In vivo, p27Kip1 significantly inhibited intimal cell proliferation and the development of a neointima after vascular injury, whereas p16Ink4 expression did not lead to a reduction in cell proliferation or neointima formation.. This different pattern of CKI inactivation of the CDKs suggests varied biological roles for p27Kip1 and p21Cip1 compared with p16Ink4 in VSMCs. p27Kip1 was initially characterized as an inhibitor of cyclin E/cdk2 phosphorylation.10 11 p27Kip1 and p21Cip1 are upregulated in several animal models of wound repair. p27Kip1 is constitutively expressed in normal arteries, is downregulated after arterial injury, and is upregulated during the later ...
cGMP Dependent Kinase Inhibitor Peptide chemical properties, What are the chemical properties of cGMP Dependent Kinase Inhibitor Peptide 82801-73-8, What are the physical properties of cGMP Dependent Kinase Inhibitor Peptide ect.
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.
Mammalian taste buds contain several specialized cell types that coordinately respond to tastants and communicate with sensory nerves. While it has long been appreciated that these cells undergo continual turnover, little is known concerning how adeq
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 ...
CDKN2A / p14ARF antibody (cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)) for ICC/IF, IHC, IHC-Fr, IHC-P, WB. Anti-CDKN2A / p14ARF pAb (GTX23642) is tested in Human samples. 100% Ab-Assurance.
Effects of exogenous p62-overexpression. (a) H23 cells were transfected with indicated siRNAs for 3 days. After transfection, cell viability was measured, and
SDI2 allows scientists to see precisely whats happening at the solid-liquid interface during the dissolution process. Learn more about this unique tool.
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This Histri was built automatically but not manually verified. As a consequence, the Histri can be incomplete or can contain errors ...
This Histri was built automatically but not manually verified. As a consequence, the Histri can be incomplete or can contain errors ...
The cortactin oncoprotein is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC), often due to amplification of the encoding gene (CTTN). While cortactin overexpression enhances invasive potential, recent research indicates that it also promotes cell proliferation, but how cortactin regulates the cell cycle machinery is unclear. In this article we report that stable short hairpin RNA-mediated cortactin knockdown in the 11q13-amplified cell line FaDu led to increased expression of the Cip/Kip cyclin-dependent kinase inhibitors (CDKIs) p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) and inhibition of S-phase entry. These effects were associated with increased binding of p21(WAF1/Cip1) and p27(Kip1) to cyclin D1- and E1-containing complexes and decreased retinoblastoma protein phosphorylation. Cortactin regulated expression of p21(WAF1/Cip1) and p27(Kip1) at the transcriptional and posttranscriptional levels, respectively. The direct roles of p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) ...
TBX3, a member of the T-box family of transcription factors, is essential in development and has emerged as an important player in the oncogenic process. TBX3 is overexpressed in several cancers and has been shown to contribute directly to tumour formation, migration and invasion. However, little is known about the molecular basis for its role in development and oncogenesis because there is a paucity of information regarding its target genes. The cyclin-dependent kinase inhibitor p21WAF1 plays a pivotal role in a myriad of processes including cell cycle arrest, senescence and apoptosis and here we provide a detailed mechanism to show that it is a direct and biologically relevant target of TBX3. Using a combination of luciferase reporter gene assays and in vitro and in vivo binding assays we show that TBX3 directly represses the p21WAF1 promoter by binding a T-element close to its initiator. Furthermore, we show that the TBX3 DNA binding domain is required for the transcriptional repression of p21WAF1
Largely on the basis of studies using the potent clastogen ionizing radiation, it has been widely assumed that up-regulation of the cyclin-dependent kinase inhibitor p21waf1cip1 in cultured cells exposed to DNA-damaging agents is contingent upon the presence of functional p53 tumor suppressor protein. Nevertheless, we demonstrate here that the model mutagen 254-nm UV light induces p21waf1cip1 protein and concomitant G1 arrest in normal human skin fibroblasts, as well as in p53-deficient fibroblasts derived from cancer-prone Li-Fraumeni syndrome patients. However, as expected, following exposure to ionizing radiation, elevated p21waf1cip1 protein levels and G1 arrest were observed only in normal fibroblasts. These data provide a prominent and clinically relevant example in which p21waf1cip1-mediated growth arrest occurs independently of p53 in human cells treated with a model DNA-damaging agent.. ...
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
The Notch family of transmembrane receptors regulates both cell fate decisions and the maintenance of adult stem cells, processes that require precise control of the cell cycle. Although Notch1 activation had previously been shown to alter the cell cycle in hematopoietic progenitor cells and to delay their commitment to the myeloid lineage, a direct link between Notch1 and cell cycle control pathways had not been established in these cells.. Sarmento et al. now find the link and show that constitutive Notch1 activation drives cell cycling by increasing the activity of cyclin-dependent kinase-2 (CDK2), a protein that promotes progression into the S phase of the cell cycle. CDK2 activation resulted from the degradation of the CDK inhibitor protein p27kip1, which was triggered by the Notch1-induced expression of a protein called SKP2-a component of a ubiquitin ligase complex that targets proteins for proteosomal degradation.. How Notch-induced changes in cell cycle kinetics influence ...
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.
Looking for exogenous p? Find out information about exogenous p. A group of substances thought to be polysaccharides of microbial origin that produce an increase in body temperature when injected into humans and some animals Explanation of exogenous p
Melanoma resistant to MAPK inhibitors (MAPKi) displays loss of fitness upon experimental MAPKi withdrawal and, clinically, may be resensitized to MAPKi therapy after a drug holiday. Here, we uncovered and therapeutically exploited the mechanisms of MAPKi addiction in MAPKi-resistant BRAFMUT or NRASMUT melanoma. MAPKi-addiction phenotypes evident upon drug withdrawal spanned transient cell-cycle slowdown to cell-death responses, the latter of which required a robust phosphorylated ERK (pERK) rebound. Generally, drug withdrawal-induced pERK rebound upregulated p38-FRA1-JUNB-CDKN1A and downregulated proliferation, but only a robust pERK rebound resulted in DNA damage and parthanatos-related cell death. Importantly, pharmacologically impairing DNA damage repair during MAPKi withdrawal augmented MAPKi addiction across the board by converting a cell-cycle deceleration to a caspase-dependent cell-death response or by furthering parthanatos-related cell death. Specifically in MEKi-resistant NRASMUT or ...
CDKN1A - CDKN1A (untagged)-Human cyclin-dependent kinase inhibitor 1A (p21, Cip1) (CDKN1A), transcript variant 2 available for purchase from OriGene - Your Gene Company.
CDKN2A - CDKN2A (untagged)-Human cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) (CDKN2A), transcript variant 4 available for purchase from OriGene - Your Gene Company.
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Although the androgen receptor (AR) has been implicated in the promotion of apoptosis in testicular cells (TSCs), the molecular pathway underlying AR-mediated apoptosis and its sensitivity to environmental hormones in TSCs and induced pluripotent stem cells (iPSCs) remain unclear. We generated the iPSCs from bovine TSCs via the electroporation of OCT4. The established iPSCs were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4 to maintain and stabilize the expression of stemness genes and their pluripotency. Apoptosis signaling was assessed after exposure to mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate. Here, we report that iPSCs were more resistant to MEHP-induced apoptosis than were original TSCs. MEHP also repressed the expression of AR and inactivated WNT signaling, and then led to the commitment of cells to apoptosis via the cyclin dependent kinase inhibitor p21CIP1. The loss of the frizzed receptor 7 and the gain of p21CIP
TGF-? is the founding member of a multifunctional family of cytokines that regulate many aspects of cell physiology, including cell growth, differentiation, motility and death and play important roles in many developmental and pathological processes. TGF-? signals by binding to a heterotetrameric complex of type I and type II serine/threonine kinase receptors. The type I receptor is phosphorylated and activated by the type II receptor and propagates the signal to the nucleus by phosphorylating and activating receptor-regulated Smad proteins (R-Smads). Once activated, the R-Smads translocate to the nucleus together with the common partner Smad, Smad4, in heteromeric complexes and regulate transcription of target genes.The cell cycle inhibitor p21Waf1/Cip1 (p21) is induced by a number of factors including p53 and TGF-?, and its high expression is associated with cellular differentiation and senescence. Low levels of p21 are required for the propagation of the cell cycle, where high levels of p21 ...
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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.
p15 INK4b antibody, Internal (cyclin-dependent kinase inhibitor 2B) for WB. Anti-p15 INK4b pAb (GTX77673) is tested in Human samples. 100% Ab-Assurance.
rs1063192 is a SNP in the cyclin-dependent kinase inhibitor 2B CDKN2B gene. A study of 432 Han Chinese patients with myocardial infarctions concluded that male subjects carrying a rs1063192(C) allele were at 0.71x decreased risk (for MI).[PMID 19272367] Myocardial Infarction ...
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 ...
In this paper, we report that (+)-preussin, a pyrrolidinol alkaloid originally identified as an antifungal agent, has growth-inhibitory and cytotoxic effects on human cancer cells. Preussin was found to be a potent inhibitor of cyclin E kinase (CDK2-cyclin E) in vitro (50% inhibitory concentration; approximately 500 nM) and to inhibit cell cycle progression into S phase. In agreement with these findings, the level of the cyclin-dependent kinase inhibitor p27(KIP-1) is increased in response to preussin treatment while the expression of both cyclin A and the transcription factor E2F-1 is down-regulated. Preussin also induces programmed cell death (apoptosis), which requires caspase activation and involves the release of cytochrome c from mitochondria. This induction of apoptosis is not blocked by high levels of Bcl-2, which usually confers resistance to chemotherapeutic agents. Taken together, our data indicate that preussin could be a promising lead compound for the development of a new class of potent
Supinoxin, also known as RX-5902, is orally bioavailable small molecule inhibitor of phosphorylated-p68 RNA helicase (P-p68), with potential anti-proliferative and antineoplastic activity. Upon oral administration, P-p68 inhibitor RX-5902 may both inhibit the activity of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein and facilitate the induction of cyclin-dependent kinase inhibitor 1 (p21). This may prevent G2/M cell cycle progression and lead to growth inhibition in tumor cells. P-p68 is overexpressed in various types of solid tumors but absent in normal tissues, and plays a role in tumor progression and metastasis. p21 is a potent cyclin-dependent kinase inhibitor which regulates cell cycle progression and mediates both growth arrest and cellular senescence. (Last updated: 6/16/2015)
ECM accumulation and ASMC proliferation are hallmarks in the development of intimal thickenings associated with the development of atherosclerotic lesions.61 Our recent work has shown that insertion of decorin-overexpressing cells into injured arteries causes a decrease in intimal volume.30 This decrease is due primarily to a decrease in ECM volume rather than a change in cell number within the intima. The results of the present in vitro study support these in vivo observations and, furthermore, suggest that the effects of decorin overexpression may involve the modulation of TGF-β activity.. An initial decrease in DNA synthesis by decorin-overexpressing cells was observed during the first 24 hours after plating, but this relative decrease disappeared at later time points. The relative decrease in LDSN cells of [3H]thymidine incorporation and increase of cyclin-dependent kinase inhibitors p21 and p27 at 24 hours after plating are similar to the effects that were reported in studies of human ...
Irreversible growth arrest is an early and integral part of squamous cell differentiation in normal human epidermal keratinocytes (NHEKs) and is assumed to be linked to the control of expression of differentiation-specific genes. In this study, we examine the link between the molecular events associated with growth arrest and the expression of differentiation genes. NHEKs that have been induced to undergo growth arrest and differentiation by suspension culture contain populations in both G1 and G2/M of the cell cycle. The irreversible growth arrest state in NHEKs is characterized by an accumulation of the hypophosphorylated forms of Rb and p130, with subsequent down-regulation of levels of Rb, up-regulation of p130 and associated down-regulation of E2F-regulated genes such as cyclin A. These events correlate with an inhibition of G1 cdk activity, mediated in part by an increase in the cdk inhibitors p21(WAF1/Cip1), p27(Kip1) and p16(Ink4a). Flow cytometric and immunoblot analysis demonstrated ...
Bastaki et al (2016) reported a case of BWS in a 9-year old Emirati boy. The patient was born to healthy, unrelated parents. He was found to have an omphalocele which contained small bowel and a small extra liver lobe. The patient was also found to suffer from cryptorchidism. Abdominal US revealed a non-progressive abdominal cyst. PCR amplification and sequencing of exons 2 and 3 of the CDKN1C gene identified a variant (c.703C,T) in the gene. According to in silico analysis results the protein change (p.Gln235X) leads to the production of a truncated protein that completely lacked the QT box. Polyphen 2 predicted that the variant was "probably damaging". The variant was not found in either of the parents DNA, marking it as a de novo mutation. ...
Cellular senescence is a fundamental cell fate playing significant and complex roles during tumorigenesis and natural aging process. However, the molecular determinants distinguishing senescence from other temporary and permanent cell-cycle arrest states such as quiescence and post-mitotic state and the specified mechanisms underlying cell-fate decisions towards senescence versus cell death in response to cellular stress stimuli remain less understood. In our studies, we aimed to employ multi-omics approaches to deepen our understanding of cellular senescence, in particular, regarding the specific molecular determinants distinguishing cellular senescence from other non-dividing cell fates. Notably, one of the most prominent features of cellular senescence differing from other non-dividing cell fates is the increased expression of senescence-associated beta-galactosidase. Because 5-Dodecanoylaminofluorescein Di-β-D-Galactopyranoside (C12FDG) is known as the substrate catalyzed by ...
2vtp: Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based X-ray crystallography and structure based drug design.
CGP74514A is a CDK1 inhibitor with potential anticancer activity. In U937 cells, CGP74514A - induced apoptosis (5 microM) became apparent within 4 hr and approached 100% by 24 hr. The pan- caspase inhibitor Boc-fmk and the caspase-8 inhibitor lETD-fmk opposed CGP74514A -induced caspase-9 activation and PARP degradation, but not cytochrome c or Smac/DIABLO release. CGP74514A -mediated apoptosis was substantially blocked by ectopic expression of full-length Bel- 2, a loop-deleted mutant Bcl-2, and Bcl-x(L). CGP74514A treatment (5 microM; 18 hr) resulted in increased p21(CIP1) expression, p27(KIP1) degradation, diminished E2F1 expression, and dephosphorylation of p34(CDC2). It also induced early (i.e., within 2 hr) inhibition of CDK1 activity and dephosphorylation of pRb, followed by pRb degradation, but did not block pRb phosphorylation at CDK2- and CDK4- specific sites. These findings indicate that the selective CDK1 inhibitor, CGP74514A , induces complex changes in cell cycle-related proteins in human
The hMPBD motif resembles a sequence in the tumor suppressor p21WAF1. This sequence (KRRQTSMTDFYHSKRRLIFS, corresponding to codons 141 to 160 of p21WAF1) binds tightly to PCNA and inhibits the in vitro replication of SV40 DNA (8). We therefore compared the ability of the synthetic peptides corresponding to wtWPBD (wild-type p21WAF1-PCNA binding domain), wtMPBD, and a chimeric MPBD-WPBD (Fig. 4B) to disrupt the MPBD-PCNA interaction. Less rPCNA bound to immobilized GST-MPBD after pretreatment of rPCNA with wtWPBD relative to pretreatment with wtMPBD (Fig. 4B). Similar results were observed when the wtWPBD and wtMPBD peptides were added to preformed GST-MPBD and PCNA complex (Fig. 4B). Because the chimeric peptide failed to compete, this result suggests that residues within the NH2- and COOH-termini of WPBD and MPBD are noninterchangeable and may contain unique PCNA-binding determinants.. What is the relation among MCMT, PCNA, and p21WAF1 in intact cells? Surprisingly, analysis of asynchronous ...
Cyclin-dependent Kinase Inhibitor (CKI); Inhibitor Of Cdc28-Clb Kinase Complexes That Controls G1/S Phase Transition, Preventing Premature S Phase And Ensuring Genomic Integrity; Phosphorylated By Clb5/6-Cdk1 And Cln1/2-Cdk1 Kinase Which Regulate Timing Of Sic1p Degradation; Phosphorylation Targets Sic1p For SCF(CDC4)-dependent Turnover; Functional Homolog Of Mammalian Kip1
Mus musculus ATCC ® 63340™ Designation: CMV-p57 TypeStrain=False Application: in another host, produces protein cyclin-dependent kinase inhibitor 1C (p57, Kip2) P57, kinase inhibitory protein 2 of cyclins (p57)
Evaluation of Coupled Nuclear and Cytoplasmic p53 Dynamics: 10.4018/978-1-4666-3604-0.ch061: The tumor suppressor protein p53 predominantly serves as a sequence specific transcription factor that may be activated upon exposure to diverse stimuli. One
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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.. ...
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?
Telomere attrition is usually a natural process that occurs due to inadequate telomere maintenance. expansion of DC cells can become partially overcome PD173074 by reducing O2 pressure from 21% to 4%. Further, repairing telomerase activity or inhibiting p53 or p21WAF/CIP significantly mitigated growth inhibition as well as caused a significant decrease in steady-state levels of superoxide. Our results support a model in which telomerase insufficiency in DC prospects to p21WAF/CIP signaling, p53, to cause improved steady-state levels of superoxide, metabolic oxidative stress, and senescence. 14, 985C997. Intro Cellular ageing entails the connection between biological programming and several environmental factors that culminate in cells dropping the ability to proliferate and becoming senescent. Two well-characterized intracellular mechanisms that are believed to induce senescence are telomere shortening and oxidative stress, PD173074 both of which are thought to become causative factors in ageing ...
MicroRNAs (miRNA) have tumor suppressive and oncogenic potential in human cancer, but whether and how miRNAs control cell cycle progression is not understood. To address this question, we carried out a comprehensive analysis of miRNA expression during serum stimulation of quiescent human cells. Time course analyses revealed that four miRNAs are up-regulated and |100 miRNAs are down-regulated, as cells progress beyond the G(1)-S phase transition. We analyzed the function of two up-regulated miRNAs (miR-221 and miR-222) that are both predicted to target the cell growth suppressive cyclin-dependent kinase inhibitors p27 and p57. Our results show that miR-221 and miR-222 both directly target the 3 untranslated regions of p27 and p57 mRNAs to reduce reporter gene expression, as well as diminish p27 and p57 protein levels. Functional studies show that miR-221 and miR-222 prevent quiescence when elevated during growth factor deprivation and induce precocious S-phase entry, thereby triggering cell death. Thus,
Studies suggest that Hsf4 expression correlates with its role in cell growth and differentiation. However, the role of Hsf4 in tumorigenesis in vivo remains unexplored. In this article, we provide evidence that absence of the Hsf4 gene suppresses evolution of spontaneous tumors arising in p53- or Arf-deficient mice. Furthermore, deletion of hsf4 alters the tumor spectrum by significantly inhibiting development of lymphomas that are normally observed in the majority of mice lacking p53 or Arf tumor suppressor genes. Using mouse embryo fibroblasts deficient in the hsf4 gene, we have found that these cells exhibit reduced proliferation that is associated with induction of senescence and senescence-associated β-galactosidase (SA-β-gal). Cellular senescence in hsf4-deficient cells is associated with the increased expression of the cyclin-dependent kinase inhibitors, p21 and p27 proteins. Consistent with the cellular senescence observed in vitro, specific normal tissues of hsf4−/− mice and ...
Human Crif1 is a protein with multiple functions, playing important roles in embryonic development, cellular stress, cell cycle regulation and mitochondrial membrane integrity. CRIF1 is coined to play a regulatory role in the Bone Marrow microenvironment-induced leukemia cell cycle arrest possibly through interacting with CDK2 and acting as a cyclin-dependent kinase inhibitor ...
MicroRNA-200b and microRNA-200c (miR-200b/c) are 2 of the most frequently upregulated oncomiRs in intestines cancer cells. cell lines. Additionally, we confirmed that dominance of RECK by miR-200b/c therefore brought about SKP2 (S-phase kinase-associated proteins 2) level and g27Kip1 (also known as cyclin-dependent kinase inhibitor 1B) destruction in intestines cancers cells, which promotes cancer cell proliferation […]. Read More ». ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
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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 difference between CIP & CIPA is that in CIP the person only cant feel pain but in case of CIPA the person cannot sweat and probably has malformations in his/ her body. ...
The human cyclin-dependent kinase inhibitor 2A (CDKN2A) gene generates several transcript variants that differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported. One of these, cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) or p16INK4a, interacts with, and sequesters, the E3 ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. Thus, p16-INK4a functions as a tumor suppressor in a variety of cells. Mutations in the CDKN2A gene are often found in many tumors. p16INK4a is also suggested to play a role in controlling cell proliferation and apoptosis during mammary gland development. p16-INK4a is also known as cyclin-dependent kinase 4 inhibitor A, CDK4 inhibitor p16-INK4, cell cycle negative regulator beta, multiple tumor suppressor 1 (MTS-1), ARF, MLM, p14, p16, p19, CMM2, INK4, INK4A, TP16, CDK4I, CDKN2, p14-ARF, p19-ARF, and p16-INK4.. ...
The non-receptor-type tyrosine kinase c-Abl functions as a cytoplasmic signal transducer upon activation of cell-surface receptors. c-Abl is also involved in DDR (DNA-damage response), which is initiated in the nucleus, whereas its molecular functions in DDR are not fully understood. In the present study, we found that c-Abl phosphorylates JunB, a member of the AP-1 (activator protein 1) transcription factor family. Because JunB was suggested to be involved in DDR, we analysed the role of c-Abl-mediated phosphorylation of JunB in DDR. We first analysed phosphorylation sites of JunB and found that c-Abl majorly phosphorylates JunB at Tyr173, Tyr182 and Tyr188. Because c-Abl promotes expression of the cyclin-dependent kinase inhibitor p21 upon stimulation with the DNA-damaging agent Adriamycin (doxorubicin), we analysed the involvement of JunB in Adriamycin-induced p21 expression. We found that JunB suppresses p21 induction through inhibition of its promoter activity. The phosphomimetic JunB, ...
Genetic variation at the chromosome 9p21 risk locus promotes cardiovascular disease; however, it is unclear how or which proteins encoded at this locus contribute to disease. We have previously demonstrated that loss of one candidate gene at this locus, cyclin-dependent kinase inhibitor 2B (Cdkn2b), in mice promotes vascular SMC apoptosis and aneurysm progression. Here, we investigated the role of Cdnk2b in atherogenesis and found that in a mouse model of atherosclerosis, deletion of Cdnk2b promoted advanced development of atherosclerotic plaques composed of large necrotic cores. Furthermore, human carriers of the 9p21 risk allele had reduced expression of CDKN2B in atherosclerotic plaques, which was associated with impaired expression of calreticulin, a ligand required for activation of engulfment receptors on phagocytic cells. As a result of decreased calreticulin, CDKN2B-deficient apoptotic bodies were resistant to efferocytosis and not efficiently cleared by neighboring macrophages. These ...
Clone REA756 recognizes the human CD20L, an intracytoplasmic membrane protein, which is also known as Htm4 or MS4A3. It is present specifically in hematopoietic cells and tissues. CD20L functions as a hematopoietic modulator for the G1-S cell cycle transition. It binds to cyclin-dependent kinase inhibitor 3 (CDKN3/KAP) and modulates the level of phosphorylation of cyclin-dependent kinase 2 (CDK2). Additional information: Clone REA756 displays negligible binding to Fc receptors. - Österreich
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CDK5 knockdown induces p53-dependent growth inhibition, apoptosis and G1 arrest.(A, B) Knockdown of p53 reduced CDK5 knockdown-induced apoptosis (A) and G1 arre
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.
It has been demonstrated that the p53 pathway plays an important role in HIV-1 infection. Previous work from our lab has established a model demonstrating how p53 could become inactivated in HIV-1...
TBX3, a member of the T-box family of transcription factors, is essential in development and has emerged as an important player in the oncogenic process. TBX3 is overexpressed in several cancers and has been shown to contribute directly to tumour formation, migration and invasion. However, little is known about the molecular basis for its role in development and oncogenesis because there is a paucity of information regarding its target genes. The cyclin-dependent kinase inhibitor p21WAF1 plays a pivotal role in a myriad of processes including cell cycle arrest, senescence and apoptosis and here we provide a detailed mechanism to show that it is a direct and biologically relevant target of TBX3. Using a combination of luciferase reporter gene assays and in vitro and in vivo binding assays we show that TBX3 directly represses the p21WAF1 promoter by binding a T-element close to its initiator. Furthermore, we show that the TBX3 DNA binding domain is required for the transcriptional repression of p21WAF1
... 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 ...
The action of dexamethasone is initiated by, and strictly dependent upon, the interaction of the drug with its receptor followed by its translocation into the nucleus where modulates gene expression. Where the drug localizes at the intranuclear level is not yet known. We aimed to study the localization of the drug in nuclear lipid microdomains rich in sphingomyelin content that anchor active chromatin and act as platform for transcription modulation. The study was performed in non-Hodgkins T cell human lymphoblastic lymphoma (SUP-T1 cell line). We found that when dexamethasone enters into the nucleus it localizes in nuclear lipid microdomains where influences sphingomyelin metabolism. This is followed after 24 h by a cell cycle block accompanied by the up-regulation of cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin-dependent kinase inhibitor 1B (CDKN1B), growth arrest and DNA-damage 45A (GADD45A), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) genes and by the reduction of signal
p21WAF1/CIP1 protein is a cyclin-dependent kinase inhibitor, discovered to be a downstream effector of p53-dependent cell cycle regulation. In order to elucidate the significance of p21 expression in lung adenocarcinomas, we performed immunohistochemical analysis of p21, p53 and Ki-67 expression in surgically resected lung adenocarcinomas. In non-neoplastic tissue, a few bronchial and bronchiolar suprabasal and ciliated cells, and a few type II alveolar cells and alveolar macrophages in the peripheral lung, were p21 positive, but the positive rate in normal lung tissue was very low (,1%). All 91 lung adenocarcinomas examined showed p21 immunoreactivity: 39 cases (42.9%) and 52 cases (57.1%) showed high and low p21 expression levels, respectively. There was no significant correlation between p21 expression and p53 expression, the loss of heterozygosity status of the p53 gene, histological grade determined by the predominant histology, lymph node metastasis, pathological stage, tumor size, smoking ...
We have previously shown that Nodal and ALK7 are expressed in human placenta (Roberts et al., 2003) and that Nodal signalling through ALK7 inhibits trophoblast cell proliferation (Munir et al., 2004), migration and invasion (Nadeem et al., 2011). In this study, we provided evidence that p27 is a key mediator of Nodal signalling in trophoblast cells. We found that Nodal not only upregulated p27 expression, but also induced p27 and CDK2 translocation to the cytoplasm, leading to inhibition of cell proliferation and migration/invasion.. The present study demonstrates that Nodal upregulates p27 mRNA and protein levels through multiple mechanisms. First, we found that in the presence of a transcription inhibitor, Nodal slowed down the decay of p27 mRNA. Second, we observed that Nodal increased p27 levels over a long period of time and this effect was still evident when protein translation was inhibited, suggesting that Nodal increases the p27 protein stability. This notion is further supported by the ...
p27/Kip1 antibody to detect human cyclin-dependent kinase inhibitor 1. Validated on up to 12 cell lysates for western blotting. Try a trial size today.
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 ...
Cellular senescence is a normal consequence of aging, resulting from lifelong accumulation of DNA damage that triggers an end to cell replication. Although senescent cells no longer divide, they persist in their tissue of origin and develop characteristics that can hasten and exacerbate age-related disease. This series addresses the contribution of cellular senescence to cardiovascular, neurodegenerative, and arthritic disorders as well as the senescent phenotypes in various tissues and cell types. In addition to their cell-intrinsic effects, senescent cells develop the ability to negatively influence healthy neighboring cells and immune cells by secreting senescence-associated set of cytokines and mediators known as the SASP. These reviews also highlight ongoing efforts to accurately identify, target, and eliminate senescent cells or otherwise combat their deleterious effects in disease. One day, this work may provide the basis for therapies targeting aging cells in multiple organs.. ...
The purpose of the study was to evaluate the effect of increasing the WAF program beyond the 13,700 figure programmed for FY 1976. Using a Steady-state simulation model, the effect of WAF programs representing two, four, and six percent of total enlisted authorizations was computed for the total force and for certain career fields. (Author)(*AIR FORCE PERSONNEL
The tumor suppressor protein p53 is often referred to as the guardian of the genome. In the past, controversial findings have been presented for the role of ...
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Many nations are currently working on Critical Infrastructure Protection (CIP) programmes, often facing similar issues and challenges. The sharing of ...

Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism | PNASTransforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism | PNAS

... p21 (WAF1, Cip1), p27Kip1, p16, and p15INK4B, that physically associate with cyclins, cyclin-dependent kinases, or cyclin-Cdk ... Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism. M B ... Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism ... Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism ...
more infohttps://www.pnas.org/content/92/12/5545?ijkey=276758d6ada53138fef0e425ac24f3df5e0ed4b5&keytype2=tf_ipsecsha

Cooperative repression of cyclin-dependent kinase inhibitor p21 gene expression by hepatitis B virus X protein and hepatitis C...Cooperative repression of cyclin-dependent kinase inhibitor p21 gene expression by hepatitis B virus X protein and hepatitis C...

Cooperative repression of cyclin-dependent kinase inhibitor p21 gene expression by hepatitis B virus X protein and hepatitis C ... and HCV core protein additively repress the universal cyclin-dependent kinase inhibitor p21 gene at the transcription level. ... The transforming growth factor-beta responsive element and Sp1 site of the p21 promoter were responsible for the effect of HCV ... Furthermore, cell growth was additively stimulated by them, suggesting that additive repression of the p21 might be important ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/11997040?dopt=Abstract

The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells. | Molecular...The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells. | Molecular...

The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells.. W Poluha, D ... The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells. ... The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells. ... The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells. ...
more infohttps://mcb.asm.org/content/16/4/1335/article-info

Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in...Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in...

1994) The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 369:574-578. ... Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in ... Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in ... Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in ...
more infohttps://mcb.asm.org/content/19/3/2109?ijkey=38b636c2d2fdaebcd4d10225d0fe25bfb0983fec&keytype2=tf_ipsecsha

Adenovirus-mediated over-expression of the cyclin/cyclin-dependent kinase inhibitor, p21 inhibits vascular smooth muscle cell...Adenovirus-mediated over-expression of the cyclin/cyclin-dependent kinase inhibitor, p21 inhibits vascular smooth muscle cell...

The p21 protein is a negative regulator of mammalian cell cycle progression that functions both by inhibiting cyclin dependent ... This p21-associated cell cycle arrest is associated both with significant inhibition of the phosphorylation of the ... In addition, we demonstrate that localized arterial infection with a p21-encoding adenovirus at the time of balloon angioplasty ... Taken together, these studies demonstrate the important role of p21 in regulating Rb phosphorylation and cell cycle progression ...
more infohttps://www.semanticscholar.org/paper/Adenovirus-mediated-over-expression-of-the-kinase-Chang-Barr/37361bfe1af5c61a7846b700486a3f24825c455d

Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cells -...Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cells -...

... cyclin-dependent kinase (Cdk), and many others. Expression of the p21 gene is mainly regulated at the transcriptional level. By ... Transfection of recombinant constructs bearing mutations in the p21 NFI site demonstrated that NFI acts as a repressor of p21 ... thereby establishing a role for NFI in the cell cycle dependent expression of p21. ... Inhibition of NFI in human skin fibroblasts through RNAi considerably increased p21 promoter activity suggesting that NFI is a ...
more infohttps://www.semanticscholar.org/paper/Transcriptional-regulation-of-the-cyclin-dependent-Ouellet-Vigneault/12d2c63fe6866f1141b49ca4736897bdadbacdd8

The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.  - PubMed - NCBIThe p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. - PubMed - NCBI

The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.. Harper JW1, Adami GR, Wei N, ... The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has been implicated in the control of the G1 to S ... tight-binding inhibitor of Cdks and can inhibit the phosphorylation of Rb by cyclin A-Cdk2, cyclin E-Cdk2, cyclin D1-Cdk4, and ... Cyclin-Dependent Kinase 2. *Cyclin-Dependent Kinase Inhibitor p21. *Cyclin-Dependent Kinases* ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/8242751?dopt=Abstract

Inhibitory Effect of Ginseng on Breast Cancer Cell Line Growth Via Up-Regulation of Cyclin Dependent Kinase Inhibitor, p21 and...Inhibitory Effect of Ginseng on Breast Cancer Cell Line Growth Via Up-Regulation of Cyclin Dependent Kinase Inhibitor, p21 and...

Results: The treatment resulted in inhibition of cell proliferation in a dose-and time-dependent manner. p53, p21WAF1and ... "Inhibitory Effect of Ginseng on Breast Cancer Cell Line Growth Via Up-Regulation of Cyclin Dependent Kinase Inhibitor, p21 and ... Inhibitory Effect of Ginseng on Breast Cancer Cell Line Growth Via Up-Regulation of Cyclin Dependent Kinase Inhibitor, p21 and ... Inhibitory Effect of Ginseng on Breast Cancer Cell Line Growth Via Up-Regulation of Cyclin Dependent Kinase Inhibitor, p21 and ...
more infohttp://journal.waocp.org/article_41318.html

Cyclin-dependent kinase inhibitor p21 modulates the DNA primer-template recognition complex  - CSHL Scientific Digital...Cyclin-dependent kinase inhibitor p21 modulates the DNA primer-template recognition complex - CSHL Scientific Digital...

The p21 protein, a cyclin-dependent kinase (CDK) inhibitor, is capable of binding to both cyclin-CDK and the proliferating cell ... Dependent Kinase Inhibitor p21 Cyclins metabolism DNA Primers DNA Replication DNA-Binding Proteins metabolism Enzyme Inhibitors ... Waga, S., Stillman, B. (July 1998) Cyclin-dependent kinase inhibitor p21 modulates the DNA primer-template recognition complex. ... Cyclin-dependent kinase inhibitor p21 modulates the DNA primer-template recognition complex ...
more infohttp://repository.cshl.edu/id/eprint/25132/

Variation in transcriptional regulation of cyclin dependent kinase inhibitor p21 waf1/cip1 among human bronchogenic carcinomas ...Variation in transcriptional regulation of cyclin dependent kinase inhibitor p21 waf1/cip1 among human bronchogenic carcinomas ...

The p53 homolog p73, contributes to this control by directly upregulating the cyclin dependent kinase inhibitor, p21waf1/cip1. ... Here we provide evidence that p73 upregulates p21 TA in BC tissues and upregulated p21 TA may result from E2F1 upregulation of ... Among BC cell lines with inactivated p53 and wild type p73 (N = 7) there was positive correlation between p73α and p21 TA (p , ... siRNA mediated reduction of p73 TA in the N417 BC cell line was associated with a significant reduction in p21 TA level (p , ...
more infohttps://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-4-23/email/correspondent/c1/new

The T-box transcription factor TBX3 drives proliferation by direct repression of the p21 WAF1 cyclin-dependent kinase inhibitor...The T-box transcription factor TBX3 drives proliferation by direct repression of the p21 WAF1 cyclin-dependent kinase inhibitor...

The cyclin-dependent kinase inhibitor p21WAF1 plays a pivotal role in a myriad of processes including cell cycle arrest, ... The T-box transcription factor TBX3 drives proliferation by direct repression of the p21WAF1 cyclin-dependent kinase inhibitor ... Phosphorylation of TBX3 at SP190 can affect its ability to repress p21. a Alignment showing conservation of the S190 residue ( ... b ATDC5 and SW1353 cells were co-transfected with a p21 promoter luciferase reporter construct together with pCMV empty, TBX3 ...
more infohttps://celldiv.biomedcentral.com/articles/10.1186/s13008-016-0019-0/figures/4

The expression of cyclin-dependent kinase inhibitors p15, p16, p21, and p27 during ovarian follicle growth initiation in the...The expression of cyclin-dependent kinase inhibitors p15, p16, p21, and p27 during ovarian follicle growth initiation in the...

... a cyclin dependent kinase (CDK), and a cyclin dependent kinase inhibitor (CDKI). The progression of cells through the cell ... cyclin-dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene. 1995, 11: 211 ... The expression of cyclin-dependent kinase inhibitors p15, p16, p21, and p27 during ovarian follicle growth initiation in the ... Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. Two major classes of CDK ...
more infohttps://rbej.biomedcentral.com/articles/10.1186/1477-7827-1-41

Association between polymorphism in p21[WAF1/CIP1]cyclin -dependent kinase inhibitor gene and human oral cancer - Virtual...Association between polymorphism in p21[WAF1/CIP1]cyclin -dependent kinase inhibitor gene and human oral cancer - Virtual...

The cyclin-dependent kinase inhibitor gene p21 [Waf/Cip1] plays a central role in inducing cellular growth arrest, terminal ... Association between polymorphism in p21[WAF1/CIP1]cyclin -dependent kinase inhibitor gene and human oral cancer Med. J. Cairo ... Association between polymorphism in p21[WAF1/CIP1]cyclin -dependent kinase inhibitor gene and human oral cancer ... Association between polymorphism in p21[WAF1/CIP1]cyclin -dependent kinase inhibitor gene and human oral cancer, Med. J. Cairo ...
more infohttps://vlibrary.emro.who.int/imemr/association-between-polymorphism-in-p21waf1-cip1cyclin-dependent-kinase-inhibitor-gene-and-human-oral-cancer/

April 2013 - Volume 32 - Issue 4 : CorneaApril 2013 - Volume 32 - Issue 4 : Cornea

Tissue Microarray Analysis of Cyclin-Dependent Kinase Inhibitors p21 and p16 in Fuchs Dystrophy. Matthaei, Mario; Lackner, Eva- ... Vascular Endothelial Growth Factor Inhibitors for Treatment of Corneal Neovascularization: A Meta-Analysis. Papathanassiou, ...
more infohttps://journals.lww.com/corneajrnl/Abstract/2013/04000/href

Cell Growth Arrest and Induction of Cyclin-Dependent Kinase Inhibitor p21WAF1/CIP1 Mediated by STAT1 | ScienceCell Growth Arrest and Induction of Cyclin-Dependent Kinase Inhibitor p21WAF1/CIP1 Mediated by STAT1 | Science

Cell Growth Arrest and Induction of Cyclin-Dependent Kinase Inhibitor p21WAF1/CIP1 Mediated by STAT1 ... Cell Growth Arrest and Induction of Cyclin-Dependent Kinase Inhibitor p21WAF1/CIP1 Mediated by STAT1 ... Cell Growth Arrest and Induction of Cyclin-Dependent Kinase Inhibitor p21WAF1/CIP1 Mediated by STAT1 ... Cell Growth Arrest and Induction of Cyclin-Dependent Kinase Inhibitor p21WAF1/CIP1 Mediated by STAT1 ...
more infohttps://science.sciencemag.org/content/272/5262/719?ijkey=7033821d63246afd143d29b80afea384144b03dc&keytype2=tf_ipsecsha

PI3K-Akt Signaling | www.antibodies-online.comPI3K-Akt Signaling | www.antibodies-online.com

This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin- ... Cyclin-Dependent Kinase 2): CDK2 antibodies CDK2 ELISA Kits CDK2 Proteins CDK2AP2 (Cyclin-Dependent Kinase 2 Associated Protein ... Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which ... MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8): MAP3K8 antibodies MAP3K8 ELISA Kits MAP3K8 Proteins ...
more infohttps://www.antibodies-online.com/pi3k-akt-signaling-pathway-4/

Dong-Hun BaeDong-Hun Bae

Transcriptional regulation of the cyclin-dependent kinase inhibitor, p21, by the chelator, Dp44mT.. Authors:. Rayan S Moussa ...
more infohttps://www.pubfacts.com/author/Dong-Hun+Bae

Factors underlying the cell growth-related bystander responses to alpha particles.Factors underlying the cell growth-related bystander responses to alpha particles.

Cyclin-Dependent Kinase Inhibitor p21. Cyclins / metabolism. Dose-Response Relationship, Radiation. Fibroblasts / cytology*, ... 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Transforming Growth Factor beta; 0/Tumor ...
more infohttp://www.biomedsearch.com/nih/Factors-underlying-cell-growth-related/10728689.html

Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21.Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21.

Cyclin-Dependent Kinase Inhibitor p21. Cyclin-Dependent Kinases / antagonists & inhibitors*. Cyclins / physiology*. DNA Damage ... 0/Antineoplastic Agents; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Enzyme Inhibitors; 0/ ... Here we show that p21 WAF1/CIP1, the prototype inhibitor of cyclin-dependent kinases (CDKs), is required for this coordination ... 10620399 - Changes in cyclin dependent kinase expression and activity accompanying lens fiber cell.... 3722629 - Intracellular ...
more infohttp://www.biomedsearch.com/nih/Uncoupling-S-phase-mitosis-induced/8649519.html

What is the role of chemoimmunotherapy in the treatment of relapsed/refractory DLBCL?What is the role of chemoimmunotherapy in the treatment of relapsed/refractory DLBCL?

... p21, inhibitor of cyclin-dependent kinases. ... PIP3 is generated as a result of BCR-dependent PI3K activation ... PI3K, phosphatidylinositide-3 kinase; AKT, protein kinase B; PTEN, phosphatase and tensin homolog; PIP2, phosphatidylinositol-4 ... B-cell receptor signaling activates PI3K-mediated activation of the kinase AKT, which activates many downstream signaling ... 5-bisphosphate; PIP3, phosphatidylinositol-4,5-trisphosphate; IKK, IkB kinase; mTOR, mammalian target of rapamycin; FoxO, ...
more infohttps://www.medscape.com/answers/202969-188169/987540-overview

What is the role of chemoimmunotherapy in the treatment of relapsed/refractory DLBCL?What is the role of chemoimmunotherapy in the treatment of relapsed/refractory DLBCL?

... p21, inhibitor of cyclin-dependent kinases. ... PIP3 is generated as a result of BCR-dependent PI3K activation ... PI3K, phosphatidylinositide-3 kinase; AKT, protein kinase B; PTEN, phosphatase and tensin homolog; PIP2, phosphatidylinositol-4 ... B-cell receptor signaling activates PI3K-mediated activation of the kinase AKT, which activates many downstream signaling ... 5-bisphosphate; PIP3, phosphatidylinositol-4,5-trisphosphate; IKK, IkB kinase; mTOR, mammalian target of rapamycin; FoxO, ...
more infohttps://www.medscape.com/answers/202969-188169/2004902-overview

Up-Regulation of MicroRNA-21 Correlates with Lower Kidney Cancer SurvivalUp-Regulation of MicroRNA-21 Correlates with Lower Kidney Cancer Survival

miR-21 increases the expression of cyclin dependent kinase inhibitor CDKN1A (p21) To see the effect of miR-21 expression on ... of p21 and p38 MAP kinases after the inhibition of miR-21 and decreased expression of cyclins and cyclin dependent kinases. ... One of the genes up regulated in the PCR array after the inhibition of miR-21 was the cyclin dependent kinase inhibitor, CDKN1A ... Western blot analysis showed an increase in the expression of p21 and p38 MAP kinase genes and a reduction in cyclin E2. ...
more infohttp://pubmedcentralcanada.ca/pmcc/articles/PMC3275568/?lang=en-ca

MEDLINE - Resultado p gina 1
	MEDLINE - Resultado p gina 1

0 (Apoptosis Regulatory Proteins); 0 (Cyclin-Dependent Kinase Inhibitor p21); 0 (DNA-Binding Proteins); 0 (TP53 protein, human ... Inibidor de Quinase Dependente de Ciclina p21/metabolismo. Dano ao DNA/fisiologia. Prote na p300 Associada a E1A. C lulas ... ZNF509L and -S1 inhibit cell proliferation by activating p21/CDKN1A and RB transcription, respectively. When cells are exposed ...
more infohttp://bases.bireme.br/cgi-bin/wxislind.exe/iah/online/?IsisScript=iah/iah.xis&nextAction=lnk&base=MEDLINE&lang=p&format=detailed.pft&indexSearch=EX&exprSearch=B01.050.150.900.649.313.750.377.750.630

Template:PBB/1026 - WikipediaTemplate:PBB/1026 - Wikipedia

Cyclin-dependent kinase inhibitor 1A (p21, Cip1). Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human ... cyclin-dependent protein serine/threonine kinase inhibitor activity. • protein binding. • cyclin-dependent protein kinase ... PCNA-p21 complex. Biological process. • regulation of cyclin-dependent protein serine/threonine kinase activity. • G1/S ... cyclin-dependent protein kinase holoenzyme complex. • nucleus. • nucleoplasm. • cytosol. • intracellular membrane-bounded ...
more infohttps://en.wikipedia.org/wiki/Template:PBB/1026
  • Through its binding to PCNA, p21 can regulate the function of PCNA differentially in replication and repair. (cshl.edu)
  • To gain an understanding of the precise mechanism by which p21 affects PCNA function, we have designed a new assay for replication factor C (RFC)-catalyzed loading of PCNA onto DNA, a method that utilizes a primer-template DNA attached to agarose beads via biotin-streptavidin. (cshl.edu)
  • rather, p21 formed a stable complex with PCNA on the DNA. (cshl.edu)
  • In contrast, the formation of a p21-PCNA complex on the DNA resulted in the displacement of RFC from the DNA. (cshl.edu)
  • The nonhydrolyzable analogs of ATP, adenosine-5'-O-(3-thiotriphosphate) (ATPgammaS) and adenyl-imidodiphosphate, each stabilized the primer recognition complex containing RFC and PCNA in the absence of p21. (cshl.edu)
  • We propose that p21 stimulates the dissociation of the RFC from the PCNA-DNA complex in a process that requires ATP hydrolysis and then inhibits subsequent PCNA-dependent events in DNA replication. (cshl.edu)
  • We also suggest that the p21-PCNA complex that remains attached to DNA might function to tether cyclin-CDK complexes to specific regions of the genome. (cshl.edu)
  • PCNA is a co-factor of cyclin-D and it makes a complex with cyclin-D, a cyclin dependent kinase (CDK), and a cyclin dependent kinase inhibitor (CDKI). (biomedcentral.com)
  • Specifically, p21 has a high affinity for the PIP-box binding region on PCNA, binding of p21 to this region is proposed to block the binding of processivity factors necessary for PCNA dependent S-phase DNA synthesis, but not PCNA dependent nucleotide excision repair (NER). (wikipedia.org)
  • Studies have also demonstrated that the E3 ubiquitin ligase complex CRL4Cdt2 degrades p21 in a PCNA dependent manner over S-phase, necessary to prevent p21 dependent re-replication, as well as in response to UV irradiation. (wikipedia.org)
  • In the absence of p21, DNA-damaged cells arrest in a G2-like state, but then undergo additional S phases without intervening normal mitoses. (biomedsearch.com)
  • Taken together, these findings suggest that TGF-beta can induce p21 through a p53-independent pathway. (pnas.org)
  • For both cell lines, RP215 and anti-antigen receptors were found to regulate similarly and consistently a number of genes including NFκB-1, IgG, P21, Cyclin D1, ribosomal P1 and c-fos with only exceptions for EGFR and ribosomal P0. (omicsonline.org)
  • As such, p21 acts as an effective inhibitor of DNA S-phase DNA synthesis though permits NER, leading to the proposal that p21 acts to preferentially select polymerase processivity factors depending on the context of DNA synthesis. (wikipedia.org)
  • p21 has been previously shown to be transcriptionally induced by DNA damage through p53 as a mediator. (pnas.org)
  • Recent work exploring p21 activation in response to DNA damage at a single-cell level have demonstrated that pulsatile p53 activity leads to subsequent pulses of p21, and that the strength of p21 activation is cell cycle phase dependent. (wikipedia.org)
  • Studies of human embryonic stem cells (hESCs) commonly report the nonfunctional p53-p21 axis of the G1/S checkpoint pathway, and its relevance for cell cycle regulation and the DNA damage response (DDR). (wikipedia.org)
  • D-type cyclins are usually synthesized by mid-G1 phase and accumulate to a maximum as cells advance through the G1/S boundary. (biomedcentral.com)
  • Working in mouse models, it was also shown that whilst mice lacking p21 were healthy, spontaneous tumours developed and G1 checkpoint control was compromised in cells derived from these mice. (wikipedia.org)
  • Specifically it contains a Cy1 motif in the N-terminal half, and weaker Cy2 motif in the C-terminal domain that allow it to bind CDK in a region that blocks its ability to complex with cyclins and thus prevent CDK activation. (wikipedia.org)
  • RFC in the ATPgammaS-activated complex was no longer displaced from the DNA by p21. (cshl.edu)