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.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Cyclin-Dependent 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.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.Cyclins: A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.Cyclin-Dependent Kinase 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.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.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 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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.Cell Line, Tumor: A cell line derived from cultured tumor cells.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.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.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.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.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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 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.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.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.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.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.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.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.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.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)Cyclin D3: A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.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.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.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.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.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.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.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.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.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.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.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.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.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.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.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.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.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.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.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.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.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.Cyclin G: A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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-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.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.Cyclin A2: A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.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.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.Cell Cycle Checkpoints: Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.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-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.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.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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.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.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.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)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.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.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.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.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.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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.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.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.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.Kinetics: The rate dynamics in chemical or physical systems.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.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.G0 Phase: A quiescent state of cells during G1 PHASE.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).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.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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.DNA Replication: The process by which a DNA molecule is duplicated.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.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Mice, Inbred C57BLUp-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.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.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.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.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.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Recombinant Proteins: Proteins prepared by recombinant DNA technology.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.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.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Benzamides: BENZOIC ACID amides.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.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.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.ChromonesRNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Cell Aging: The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.PiperazinesOncogene Proteins: Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Retinoblastoma-Binding Protein 1: A ubiquitously expressed regulatory protein that contains a retinoblastoma protein binding domain and an AT-rich interactive domain. The protein may play a role in recruiting HISTONE DEACETYLASES to the site of RETINOBLASTOMA PROTEIN-containing transcriptional repressor complexes.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.p21-Activated Kinases: A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.
TGF beta 1
"Survival and cell cycle control in early hematopoiesis: role of bcl-2, and the cyclin dependent kinase inhibitors P27 and P21 ... Most immune cells (or leukocytes) secrete TGF-β1. Some T cells (e.g. regulatory T cells) release TGF-β1 to inhibit the actions ... Interleukin 1- and interleukin 2-dependent proliferation of activated T cells, and the activation of quiescent helper T cells ... It is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell ...
... of mammalian cyclin dependent kinase (CDK) inhibitors (CKIs) involved in regulating the cell cycle. The CIP/KIP family is made ... Coqueret O (2003). "New roles for p21 and p27 cell-cycle inhibitors: A function for each cell compartment?". Trends in Cell ... "Increased proteasome-dependent degredation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas". ... Toyoshima H, Hunter T (1994). "p27, a novel inhibitor of G1 cyclin/cdk protein kinase activity, is related to p21". Cell. 78: ...
"Survival and cell cycle control in early hematopoiesis: role of bcl-2, and the cyclin dependent kinase inhibitors P27 and P21 ... also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) ... "Mechanism of inhibition of proliferating cell nuclear antigen-dependent DNA synthesis by the cyclin-dependent kinase inhibitor ... "Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell ...
SCF-Skp2 mainly ubiquitinates and degrades cyclin-dependent kinase inhibitors (CKIs) such as p27 and p21 as well as the G1-/S- ... doi:10.1046/j.1365-313X.2002.01432.x. Morgan, David "Protein Degradation in Cell-Cycle Control", The Cell Cycle; Principles of ... Morgan, David "Protein Degradation in Cell-Cycle Control", The Cell Cycle; Principles of Control 2007 David Frescas and Michele ... specific cyclin E, in vivo and in vitro. Therefore, SCF-Skp2 promotes cell-cycle progression and cell growth. On the other hand ...
P27 cis-regulatory element
The p27kip1 protein is involved in cell cycle regulation and belongs to the Cip/Kip family of cyclin dependent kinase(CDK) ... "Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex". Nature. 382 (6589): 325 ... Gopfert, U; Kullmann M; Hengst L (2003). "Cell cycle-dependent translation of p27 involves a responsive element in its 5'-UTR ... January 1994). "p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle ...
Akt/PKB signaling pathway
Akt both indirectly and directly regulates cyclin-dependent kinase (CDK) inhibitors p21Cip1 and p27Kip1 , allowing cell cycle ... prevents p27 gene expression. Akt phosphorylates many proteins involved in polymerisation and stabilisation of the actin ... Liang J, Slingerland JM (2003). "Multiple Roles of the PI3K/PKB (Akt) Pathway in Cell Cycle Progression". Cell Cycle. 2 (4): ... Akt also phosphorylates MAP kinase kinase kinases (MAPKKK) upstream of the stress-activated protein kinase (SAPK) pathway. ...
Inactivation of cyclin D is triggered by several cyclin-dependent kinase inhibitor protein (CKIs) like the INK4 family (e.g. ... while p27−/− and cyclin D−/− knockouts develop normally. CDK Cyclins Cell cycle PDB: 2W96; Day PJ, Cleasby A, Tickle IJ, ... Since cell cycle progression is related to cell size, mutations in Cyclin D and its homologues show a delay in cell cycle entry ... activate cyclin D gene in response to integrin. p27kip1 and p21cip1 are cyclin-dependent kinase inhibitors (CKIs) which ...
Progression through the cell cycle is tightly regulated by cyclin-dependent kinases (CDKs), and their interactions with cyclins ... and these inhibitors induce p27 accumulation in a Skp2-dependent manner and promote cell cycle arrest. Another recent discovery ... "Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated ... It specifically recognizes and promotes the degradation of phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also ...
Cyclin-dependent kinase 6
"Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d". Nature. 395 ... CKIs or CIP/KIP family members like the protein p21 and p27 act blocking and inhibiting the assembled C-CDKs binding complex ... A Cyclin-dependent kinase 6 interacts with: CDKN2C, Cyclin D1, Cyclin D3, P16, PPM1B, and PPP2CA. Cell cycle, Mitosis, CDK, ... "Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6". Cell. 118 (4): 493-504. doi:10.1016/j.cell. ...
"In CK2 inactivated cells the cyclin dependent kinase inhibitor Sic1 is involved in cell-cycle arrest before the onset of S ... p27 CDKN1B Schwob E, Böhm T, Mendenhall MD, Nasmyth K (October 1994). "The B-type cyclin kinase inhibitor p40SIC1 controls the ... a cyclin-dependent kinase (Cdk) inhibitor, by Cdk including Pho85 kinase is required for its prompt degradation". Molecular ... "The yeast cyclin-dependent kinase inhibitor Sic1 and mammalian p27Kip1 are functional homologues with a structurally conserved ...
Cyclin-dependent kinases (CDKs) are a family of sugar kinases first discovered for their role in regulating the cell cycle. ... A cyclin-dependent kinase inhibitor (CKI) is a protein that interacts with a cyclin-CDK complex to block kinase activity, ... In mammalian cells, the CKI regulation works differently. Mammalian protein p27 (Dacapo in Drosophila) inhibits G1/S- and S- ... CDK6; cyclin D1, cyclin D2, cyclin D3 CDK7; cyclin H CDK8; cyclin C CDK9; cyclin T1, cyclin T2a, cyclin T2b, cyclin K CDK10 ...
CP110, a cell cycle-dependent CDK substrate, regulates centrosome duplication in human cells. Dev Cell. 2002, 3: 339-350 Huang ... Like all cyclin family members, cyclin E forms a complex with cyclin-dependent kinase (CDK2). Cyclin E/CDK2 regulates multiple ... The Cyclin E/CDK2 complex phosphorylates p27Kip1 (an inhibitor of Cyclin D), tagging it for degradation, thus promoting ... Cyclin E/CDK2 also phosphorylates p27 and p21 during G1 and S phases, respectively. Smad3, a key mediator of TGF-β pathway ...
This complex is one of many cyclin/cyclin-dependent kinase complexes that are the "hearts of the cell-cycle control system" and ... helps to further inhibit p27 and thus further help activate the Cyclin D/Cdk4 complex. Also, p27 acts as an inhibitor of Cyclin ... The Cyclin D/Cdk4 complex is a multi-protein structure consisting of the proteins Cyclin D and cyclin-dependent kinase 4, or ... govern the cell cycle and its progression. As its name would suggest, the cyclin-dependent kinase is only active and able to ...
p21, wolna encyklopedia
Li Y, Jenkins CW, Nichols MA, Xiong Y. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. „ ... proteasome inhibitors overcome Bcl-2 protective function and selectively accumulate the cyclin-dependent kinase inhibitor p27 ... Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell ... The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. „Cell". 75 (4), s. 805-816, 1993. ...
Factor de crecemento transformante beta 1, a enciclopedia libre
"Survival and cell cycle control in early hematopoiesis: role of bcl-2, and the cyclin dependent kinase inhibitors P27 and P21 ... Schnaper HW, Hayashida T, Hubchak SC, Poncelet AC (2003). "TGF-beta signal transduction and mesangial cell fibrogenesis". Am. J ... Gressner AM, Weiskirchen R (2006). "Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major ... "Transforming growth factor-beta 1 induces antigen-specific unresponsiveness in naive T cells". Immunol. Invest. 26 (4): 459-72 ...
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 ... CDKIs) p21 and p27. Not even upregulation of the other Class I HDACs could compensate for the loss of HDAC1. This inability to ... Many cell generations later, in the absence of the inhibitor, the increased gene expression was still expressed, showing ...
Factor de crecimiento transformante beta 1, la enciclopedia libre
Survival and cell cycle control in early hematopoiesis: role of bcl-2, and the cyclin dependent kinase inhibitors P27 and P21 ... Schnaper HW, Hayashida T, Hubchak SC, Poncelet AC (2003). «TGF-beta signal transduction and mesangial cell fibrogenesis.». Am. ... Gressner AM, Weiskirchen R (2006). «Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major ... de 2000). «Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of ...
... plays a pivotal role in G1 cell cycle progression, primarily through regulation of cyclin D1 and cyclin-dependent kinase ... inhibitors (p21 and p27) expression. These regulation pathways activate protein kinases, which subsequently modulate ... This inhibitor specifically targets Rho GTPases to prevent cell growth related to cancer. When tested on breast cancer cells, ... Similarly, RhoA's stimulation of PKN2 kinase activity regulates cell-cell adhesion through apical junction formation and ...
COP9 constitutive photomorphogenic homolog subunit 5
This protein is reported to be involved in the degradation of cyclin-dependent kinase inhibitor CDKN1B/p27Kip1. It is also ... "Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1". Nature. 408 (6809): 211-6 ... "Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1)". Oncogene. 21 (19): 3003-10. doi:10.1038/sj.onc.1205390. PMID ... Tomoda K, Kubota Y, Kato J (1999). "Degradation of the cyclin-dependent-kinase inhibitor p27Kip1 is instigated by Jab1". Nature ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... "Repression of the CDK activator Cdc25A and cell-cycle arrest by cytokine TGF-beta in cells lacking the CDK inhibitor p15". ... 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- ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... and thus regulate separate functions in cell cycle. This cyclin was found to bind to important cell cycle regulators, such as ... Cyclins function as activating subunits of enzymatic complex together with cyclin-dependent kinases (CDKs). Different cyclins ... the A-type cyclins and their associated cyclin-dependent kinases are differentially expressed in the germ-cell lineage". Dev. ...
"Survival and cell cycle control in early hematopoiesis: role of bcl-2, and the cyclin dependent kinase inhibitors P27 and P21 ... CDKN1B has been shown to interact with: AKT1, CKS1B, Cyclin D3, Cyclin E1, Cyclin-dependent kinase 2, Cyclin-dependent kinase 4 ... "Prognostic role of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer". Cancer Res. 57 (16): 3381-5. PMID ... "Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27(Kip1)". Cell. 85 (5): 721-32. doi:10.1016 ...
Woo RA, Poon RY (Jul-Aug 2003). "Cyclin-dependent kinases and S phase control in mammalian cells". Cell Cycle. 2 (4): 316-24. ... "Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex". Nature. 382 (6589): 325 ... Rosner M, Hengstschläger M (November 2004). "Tuberin binds p27 and negatively regulates its interaction with the SCF component ... Cyclin A2 belongs to the cyclin family, whose members regulate cell cycle progression by interacting with CDK kinases. Cyclin ...
... cell proliferation) and suppresses apoptosis by regulating cyclin-dependent kinase 1 (Cdk-1). PFKFB3's synthesis of F2,6BP in ... promotes cell cycle progression and suppresses apoptosis via Cdk1-mediated phosphorylation of p27". Cell Death & Disease. 5 (7 ... Boyd, Scott (April 7, 2015). "Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase PFKFB3". J. Med ... "Nuclear Targeting of 6-Phosphofructo-2-kinase (PFKFB3) Increases Proliferation via Cyclin-dependent Kinases". Journal of ...
Cyclin-dependent kinase 4
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... G1/S transition of mitotic cell cycle. • negative regulation of cyclin-dependent protein serine/threonine kinase activity ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ... CDK4, CMM3, PSK-J3, cyclin-dependent kinase 4, cyclin dependent kinase 4. ...
Cyclin-dependent kinase 4
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... Zhang JM, Wei Q, Zhao X, Paterson BM (1999). "Coupling of the cell cycle and myogenesis through the cyclin D1-dependent ... 1995). "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ...
"Direct induction of cyclin D2 by Myc contributes to cell cycle progression and sequestration of p27". The EMBO Journal. 18 (19 ... "Cyclin D- and E-dependent kinases and the p57(KIP2) inhibitor: cooperative interactions in vivo". Molecular and Cellular ... Cyclins function as regulators of cyclin-dependent kinases. Different cyclins exhibit distinct expression and degradation ... are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Molecular and Cellular Biology. 15 (5): 2672-81. PMC ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... and cell cycle arrest mediated by transcription factor DMP1 is antagonized by D-type cyclins through a cyclin-dependent-kinase- ... Hall M, Peters G (1996). "Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer". ... Cyclins function as regulators of CDKs (Cyclin-dependent kinase). Different cyclins exhibit distinct expression and degradation ...
... cyclins and cyclin-dependent kinases (CDKs), determine a cell's progress through the cell cycle. Leland H. Hartwell, R. Timothy ... As mentioned above, when some genes like the cell cycle inhibitors, RB, p53 etc. mutate, they may cause the cell to multiply ... The cip/kip family includes the genes p21, p27 and p57. They halt cell cycle in G1 phase, by binding to, and inactivating, ... Controlling the Cell Cycle The cell cycle & Cell death Transcriptional program of the cell cycle: high-resolution timing Cell ...
Cycling B-CLL cells are highly susceptible to inhibition of the proteasome: involvement of p27, early D-type cyclins, Bax, and...
... a proliferating pool of cells in proliferation centers might be involved in disease progression. We have previously described ... Although peripheral blood B-CLL cells are arrested in G0 phase of the cell cycle, ... Cell Cycle*. Cell Cycle Proteins / drug effects*. Cell Division / drug effects. Cyclin-Dependent Kinase Inhibitor p27. Cyclins ... 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 616-91-1/Acetylcysteine; EC 3.4.22.-/Caspases; EC 3.4.22.-/Cysteine ...
Cyclin-Dependent Kinase Inhibitor p27 Summary Report | CureHunter
... 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. ... CDK Inhibitor, p27; Cyclin Dependent Kinase Inhibitor 1B; Cyclin Dependent Kinase Inhibitor p27; Kip1 Protein, p27; p27, CDK ...
Alpha-lipoic acid induces p27Kip-dependent cell cycle arrest in non-transformed cell lines and apoptosis in tumor cell lines
... hyperacetylation of histones in vivo and has differential effects on the growth and viability of normal versus transformed cell ... Carcinoma, Squamous Cell * Cell Cycle Proteins / genetics* * Cyclin-Dependent Kinase Inhibitor p27 ... Alpha-lipoic acid induces p27Kip-dependent cell cycle arrest in non-transformed cell lines and apoptosis in tumor cell lines J ... alpha-Lipoic acid caused a post-translational elevation in the levels of the cyclin-dependent kinase inhibitor p27Kip1. Studies ...
p27(Kip1): regulation and function of a haploinsufficient tumor suppressor and its misregulation in cancer
... is to bind and inhibit cyclin/cyclin-dependent kinase complexes, thereby blocking cell cycle progression. As p27 operates at ... the heart of the cell cycle, it is perhaps not surprising that it is emerging as a key player in multiple cell fate decisions ... A major function of p27, also known as Kip1, ... Cyclin-Dependent Kinase Inhibitor p27 * Female * Genes, Tumor ... is to bind and inhibit cyclin/cyclin-dependent kinase complexes, thereby blocking cell cycle progression. As p27 operates at ...
Inhibition of cell growth and induction of G1-phase cell cycle arrest in hepatoma cells by steroid extract from Meretrix...
... has the ability to inhibit growth of hepatoma cells and to induce G1-phase cell cycle arrest in two human hepatoma cell lines ... Cyclin-Dependent Kinase Inhibitor p21 / analysis. Cyclin-Dependent Kinase Inhibitor p27 / analysis. G1 Phase / drug effects*. ... 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Intracellular Signaling Peptides and ... Cell Line, Tumor. Cell Proliferation / drug effects. Cyclin-Dependent Kinase Inhibitor p16 / analysis. ...
Lack of the Cell-Cycle Inhibitor p27Kip1 Results in Selective Increase of Transit-Amplifying Cells for Adult Neurogenesis |...
1996) Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27(Kip1). Cell 85:721-732. ... 1996) A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila ... 1998) Developmental regulation of a cyclin-dependent kinase inhibitor controls cell cycle progression in Caenorhabditis elegans ... 1996) Dacapo, a cyclin-dependent kinase inhibitor, stops cell proliferation during Drosophila development. Cell 87:1225-1235. ...
Cyclin-dependent kinase - definition of Cyclin-dependent kinase by The Free Dictionary
Cyclin-dependent kinase synonyms, Cyclin-dependent kinase pronunciation, Cyclin-dependent kinase translation, English ... dictionary definition of Cyclin-dependent kinase. n. Any of various enzymes that catalyze the transfer of a phosphate group ... Western blotting was used to measure cyclin-dependent kinase (CDK) inhibitors p21 and p27 that arrest cell cycle.. Effects of ... is a member of the CIP1/KIP1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene.. Cell cycle ...
Patent US8017749 - Compositions and methods to treat cancer with cupredoxins and CpG rich DNA - Google Patents
These methods may be used to express therapeutic or diagnostic proteins near cancer cells in a patient suffering from cancer or ... The present invention further relates to methods to express proteins near cancer cells. ... For example, the cargo compound can be a cell cycle control protein, such as p53; a cyclin-dependent kinase inhibitor, such as ... p16, p21 or p27; a suicide protein such as thymidine kinase or nitroreductase; a cytokine or other immunomodulatory protein ...
Deletion of the p27Kip1 gene restores normal development in cyclin D1-deficient mice | PNAS
In addition, D-cyclins play a kinase-independent role by sequestering cell cycle inhibitors p27Kip1 and p21Cip1. In the past, ... These proteins are believed to drive cell cycle progression by associating with their kinase partners, cyclin-dependent kinases ... Is then the ability of cyclin D1 to neutralize p27Kip1 the only relevant function of cyclin D1 in the cell cycle progression? ... in the absence of measurable cyclin D-kinase activity and are resistant to cell cycle arrest induced by D-cyclin inhibitor p16 ...
Targeting AMPK for Therapeutic Intervention in Type 2 Diabetes | IntechOpen
Cyclin-dependent kinase inhibitor 1B, controls cell cycle progression at G1. stabilization of p27; linked to autophagy. nucleus ... inhibition of mTORC1; cell cycle arrest. cytoplasm. Gwinn et al., 2008. Rb. Retinoblastoma protein; regulates cell cycle ... cell growth, cell cycle progression, mitosis, cell polarity, development, auto- and mitophagy (Amato et al., 2011; Bungard et ... cell cycle arrest, DNA repair, apoptosis. stabilization of p300-p53 interaction; controls cell cycle progression. nucleus. ...
Fight Aging! Newsletter, January 6th 2020 - Fight Aging!
... this checkpoint becomes impassable and cells enter the non-dividing state. The cyclin-dependent kinase inhibitor p27 prevents ... All normal dividing somatic cells make a cycle suspension here; but, after a certain number of reduplication cycles, ... An NMNT inhibitor improves NAD+ salvage to increase stem cell function. Nicotinamide riboside improves intestinal stem cell ... It occurs in somatic cells that have few cell divisions left, so will not spread, and these cells will die or become senescent ...
Pathobiology of ALK+ anaplastic large-cell lymphoma | Blood Journal
This effect is mediated, at least partially, via the downregulation of the cyclin-dependent kinase inhibitor p27.77,78 Gu et al ... Adenoviral-mediated transfer of p16, p21, p27, and p53 induces apoptosis and cell-cycle arrest in ALK+ ALCL cell lines and ... Inhibition of Akt increases p27Kip1 levels and induces cell cycle arrest in anaplastic large cell lymphoma. Blood 2005;105:827- ... CD30-mediated cell cycle arrest associated with induced expression of p21CIP1/WAF1 in the anaplastic large cell lymphoma cell ...
Cell Cycle-Dependent Regulation of FLIP Levels and Susceptibility to Fas-Mediated Apoptosis | The Journal of Immunology
The cyclin-dependent kinase inhibitor, p27, is present at high amounts during G0 and G1 phase and decreases as the cell enters ... Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science 269: 682 ... For cell cycle synchronization, CD3+ T cells were CD3 cross-linked in the presence of CsA for 20 h, after which cells were ... Quiescent cells (G0) and cells entering the cell cycle (G1) have a competent apoptotic machinery that is kept inactive by high ...
017613 - C57BL/6-Tg(tetO-Cdkn1b)1Scpr/J
These mice express a cyclin-dependent kinase inhibitor 1B (,i,Cdkn1b,/i,) cDNA under the direction of the tetracycline operator ... CDKN1B, or p27, is a cell cycle inhibitor protein which acts by arresting cell division at G1. Hemizygous mice are viable and ... These mice express a cyclin-dependent kinase inhibitor 1B (Cdkn1b) cDNA under the direction of the tetracycline operator. When ... These mice express a cyclin-dependent kinase inhibitor 1B (Cdkn1b) cDNA under the direction of the tetracycline operator. These ...
TRERF1 transcriptional regulating factor 1 [Homo sapiens (human)] - Gene - NCBI
TReP-132 controls cell proliferation by regulating the expression of the cyclin-dependent kinase inhibitors p21WAF1/Cip1 and ... TReP-132 is a basal cell cycle regulatory protein interacting with Sp1 to activate the p21 and p27 gene promoters. Title: TReP- ... 132 controls cell proliferation by regulating the expression of the cyclin-dependent kinase inhibitors p21WAF1/Cip1 and p27Kip1 ... locus by cell-fusion-mediated gene transfer in human breast-cancer cells. Dorssers LC, et al. Int J Cancer, 1997 Aug 7. PMID ...
Novel insights into cell cycle regulation of cell fate determination | SpringerLink
The stem/progenitor cell has long been regarded as a central cell type in development, homeostasis, and regeneration, largely ... Cloning of p27kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell, ... Extensive studies have demonstrated that cell cycle states determine cell fates, because cells in different cell cycle states ... The cell-cycle state of stem cells determines cell fate propensity. Cell, 155(1):135-147. https://doi.org/10.1016/j.cell. ...
RAS oncogenes: weaving a tumorigenic web. - PubMed - NCBI
RAS also upregulates the levels of cyclin D1 and suppresses the cyclin-dependent kinase inhibitor (CDKI) p27. The newly ... E2F transcription factors transactivate several genes that are required for cell cycle progression, including cyclin E (CCNE) ... synthesized cyclin D1 associates with and activates the cyclin-dependent kinases CDK4 and CDK6, leading to the phosphorylation ... The recruitment of macrophages by neoplastic cells (through RAS-induced nuclear factor-κB (NF-κB)-dependent production of the ...
Renal Biopsy: Use of Biomarkers as a Tool for the Diagnosis of Focal Segmental Glomerulosclerosis
... β is controlled by cell-cycle regulatory proteins. The activation of specific cyclin-dependent kinases (CDK) promotes cell ... The cyclin-CDK complex is negatively regulated by CDK inhibitors p21, p27, and p57. Podocyte injury induces the loss of ... S. Wang, J. H. Kim, K. C. Moon, H. K. Hong, and H. S. Lee, "Cell-Cycle Mechanisms Involved in Podocyte Proliferation in ... H. W. Smith and C. J. Marshall, "Regulation of cell signalling by uPAR," Nature Reviews Molecular Cell Biology, vol. 11, no. 1 ...
Regulation of the cyclin-dependent kinase inhibitor p27 by degradation and phosphorylation - Semantic Scholar
In quiescent cells p27 accumulates without an increase in mRNA or protein synthesis. Cell cycle regulation of p27 levels, both ... These inhibitors regulate the progression through G1 and the G1/S transition via the inhibition of the cyclin-dependent kinase ... p27 is a phosphoprotein and its phosphorylation is cell cycle regulated. Often phosphorylation is a signal for ubiquitination. ... quiescent cells contain a far lower amount of p27 ubiquitinating activity. The specific proteolysis of p27 is probably involved ...
Genetic rescue of cell number in a mouse model of microphthalmia: interactions between Chx10 and G1-phase cell cycle regulators...
The cyclin-dependent kinase inhibitors p19(Ink4d) and p27(Kip1) are coexpressed in select retinal cells and act cooperatively ... Nakayama, K. (1998). Cip/Kip cyclin-dependent kinase inhibitors: brakes of the cell cycle engine during development. BioEssays ... Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27(Kip1). Cell 85,721 -732. ... Toyoshima, H. and Hunter, T. (1994). p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell ...
lncRNA SNHG5 is associated with poor prognosis of bladder cancer and promotes bladder cancer cell proliferation through...
SNHG5, small nucleolar RNA host gene 5; CDK2, cyclin-dependent kinase 2; p27, cyclin-dependent kinase inhibitor 1B; si, small ... D and E) Apoptosis rate and cell cycle distribution of cells co-transfected with si-SNHG5 and si-p27 were measured by flow ... SNHG5, small nucleolar RNA host gene 5; si small interfering; p27, cyclin-dependent kinase inhibitor 1B; BC, bladder carcinoma. ... 4A, silenced SNHG5 in UMUC3 cell and 5637 cell obviously induced cell cycle arrest at G1. And flow cytometric analysis of ...
Gene disruption of p27Kip1 allows cell proliferation in the postnatal and adult organ of Corti | PNAS
Inhibitors of cell-cycle progression include the cyclin-dependent kinase inhibitors (CKIs), which function in both cell-cycle ... Here we report that the cyclin-dependent kinase inhibitor p27Kip1 is selectively expressed in the supporting-cell population of ... This suggests that release from p27Kip1-induced cell-cycle arrest is sufficient to allow supporting-cell proliferation to occur ... At the molecular level terminally differentiated cells have been shown to express high levels of cell-cycle inhibitors, in ...
p21WAF1/CIP1 Expression is Differentially Regulated by Metformin and Rapamycin
High glucose opposed metformin in regulating cell size, proliferation, and protein synthesis. These effects were associated ... Here we investigated the effect of metformin and rapamycin on mTOR-related phenotypes in cell lines of epithelial origin. This ... Several investigators have associated the expression of Cip/Kip cyclin-dependent kinase (CDK) inhibitors, p21 and p27, with ... that glomerular hypertrophy is a consequence of increased cyclin-dependent kinase inhibitor expression-mediated cell cycle ...
Vitamin D-related Therapies in Prostate Cancer | SpringerLink
Cyclin-dependent kinase inhibitor p27 as a mediator of the G1-S phase block induced by 1,25-dihydroxyvitamin D3 in HL60 cells. ... A dual block to cell cycle progression in HL-60 cells exposed to analogues of vitamin D3. Cell Proliferation 27: 37-46, 1994 ... Calcitriol induces a significant G0/G1 arrest and modulates p21Waf1/Cip1 and p27Kip1, the cyclin dependent kinase inhibitors. ... Biggs JR, Kraft AS: Inhibitors of cyclin-dependent kinase and cancer. J Mol Med 73: 509-514, 1995Google Scholar ...
Neurotransmitter receptor activation triggers p27(Kip1)and p21(CIP1) accumulation and G1 cell cycle arrest in oligodendrocyte...
1997) Cyclin-dependent kinase inhibitor p27kip1is expressed at high levels in cells that express a myelinating phenotype. J. ... 1994) Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27Kip1) of cyclin-dependent kinase 4 activation. Cell 79, ... 1997) Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of oligodendrocyte differentiation. EMBO J ... 1997) Changes in cyclin-dependent kinase 2 and p27kip1 accompany glial cell differentiation of Central Glia-4 cells. J. Biol. ...
TGF beta 1 - Wikipedia
"Survival and cell cycle control in early hematopoiesis: role of bcl-2, and the cyclin dependent kinase inhibitors P27 and P21 ... Most immune cells (or leukocytes) secrete TGF-β1. Some T cells (e.g. regulatory T cells) release TGF-β1 to inhibit the actions ... Interleukin 1- and interleukin 2-dependent proliferation of activated T cells, and the activation of quiescent helper T cells ... It is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell ...
The discovery of a new structural class of cyclin-dependent kinase inhibitors, aminoimidazo[1,2-a]pyridines | Molecular Cancer...
Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin- ... p27, cdc25A, DP1, cdh1, cdc6, and orc1 (14-18). Much of this binding specificity comes from the cyclin partner for CDK2, either ... Mechanisms of cyclin-dependent kinase regulation: structures of CDKs, their cyclin activators, and Cip and INK4 inhibitors. J ... Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists. Proc Natl Acad Sci USA. 1999;96:4325-9. ...
Treatment Strategy Suggested for Multi-Lineage Leukemia in Infants | Medpage Today
Inhibitors of an intracellular signaling enzyme could be an effective treatment for mixed lineage leukemia (MLL), a malignancy ... and transformation by a mechanism that ultimately involves destabilization of the cyclin-dependent kinase inhibitor p27Kip1. ... Inhibition of GSK3 apparently causes cell-cycle arrest, the researchers said, probably through the action of p27Kip1. Dr. ... Glycogen synthase kinase 3 (GSK3) appeared to be required for survival of MLL cells in vitro and in a mouse model of the ...
Profilin-1 overexpression inhibits proliferation of MDA-MB-231 breast cancer cells partly through p27kip1 upregulation
G1-S transition of cell cycle is inhibited by cyclin-dependent kinase inhibitors [CDKIs]. Among different CDKIs, p27 is ... E-Cadherin-dependent growth suppression is mediated by the cyclin-dependent kinase inhibitor p27(KIP1) J Cell Biol. 1998;142(2 ... Cell cycle progression is tightly regulated by coordinated activities of cyclin/cyclin-dependent kinase (CDK) complexes. The ... Pfn1 overexpression results in increased protein stability of p27kip1 (p27 - a major cyclin-dependent kinase inhibitor) and ...
Intrinsically Disordered Protein - Proteopedia, life in 3D
Cell signaling and cell cycle regulation, e.g. cyclin dependent kinase inhibitor p21Waf1/Cip1/Sdi1 ... The human p27Kip1 kinase inhibitory domain  The cyclin-dependent kinases (CDKs) have a central role in coordinating the ... Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex. Nature. 1996 Jul 25;382( ... IDPs rapid turnover in the cell allow their tight regulation as many times needed in cell signaling and cell cycle. ...
InhibitionComplexesCdk2CDKsKip1 and p21 Cip1MammalianCDK4 and CDK6Role of p27PathwayCDKN1BExtracellularNuclearExpression of p27PhaseOverexpressionDownstreamInhibit cell cycleCip1 and p27 Kip1MechanismDegradation of p27UpregulationDownregulationAccumulationProgenitorTumorsPhosphorylateTranscriptionVascular SmoothTyrosine kinase inApoptoticEpithelialProtein levelsEmbryonicCytoplasmic p27Involvement of cyclinCatalyticBinds
- Cycling B-CLL cells are highly susceptible to inhibition of the proteasome: involvement of p27, early D-type cyclins, Bax, and caspase-dependent and -independent pathways. (biomedsearch.com)
- In the present study, we investigated the effect of proteasome inhibition in proliferating B-CLL cells. (biomedsearch.com)
- CONCLUSION: Proteasome inhibition is highly effective in proliferating B-CLL cells and induces apoptosis using a caspase-dependent and -independent pathway. (biomedsearch.com)
- Inhibition of cell growth and induction of G1-phase cell cycle arrest in hepatoma cells by steroid extract from Meretrix meretrix. (biomedsearch.com)
- Inhibitors of the kinase inhibitory protein (Kip) family can also bind CDK4/cyclin D complexes, although with lower affinity than the INKs, but this event does not result in efficient functional inhibition of enzymatic activity ( Sherr and Roberts, 1995 ). (jneurosci.org)
- Inhibition of IL-2 production by cyclosporin A, or inhibition of IL-2 signaling by rapamycin or anti-IL-2 neutralizing Abs prevents the decrease in FLIP levels and confers resistance to Fas-mediated apoptosis following T cell activation. (jimmunol.org)
- TReP-132 is a novel progesterone receptor coactivator required for the inhibition of breast cancer cell growth and enhancement of differentiation by progesterone. (nih.gov)
- Therefore, this investigation has been directed at the potential role of cell-cycle inhibition in the supporting-cell population of the organ of Corti. (pnas.org)
- Moreover, we report the identification of structural features required for kinase inhibition, co-crystal structures of CDK2 in complex with initial leads, and evidence for a selective inhibition of CDK2 in tumor cells. (aacrjournals.org)
- Dr. Cleary and colleagues said the research "provides a rationale to develop inhibitors with suitable pharmacodynamic properties for clinical trials to determine whether GSK3 inhibition may have therapeutic efficacy in a distinctive subset of poor prognosis leukemia. (medpagetoday.com)
- Inhibition of GSK3 apparently causes cell-cycle arrest, the researchers said, probably through the action of p27 Kip1 . (medpagetoday.com)
- Recent reports from our lab suggest that in the presence of diabetes mellitus, elevation of extracellular signal response kinase activity may promote decreased p27 Kip1 mRNA and produce a relative resistance to mTOR inhibition. (mdpi.com)
- Because the Notch-Hes signaling pathway is crucial for neural precursor self-renewal and inhibition of premature differentiation, we asked whether the cell cycle protein p107 may be regulating the neural precursor population and progenitor differentiation by the repression of Hes1. (rupress.org)
- HDAC inhibition resulted in a transcriptional and posttranscriptional regulation of the cyclin-dependent kinase inhibitors p21 Cip1 and p27 Kip . (ahajournals.org)
- Furthermore, HDAC inhibition repressed mitogen-induced cyclin D1 mRNA expression and cyclin D1 promoter activity. (ahajournals.org)
- As a result of this differential cell cycle-regulatory gene expression by HDAC inhibition, the retinoblastoma protein retains a transcriptional repression of its downstream target genes required for S phase entry. (ahajournals.org)
- Finally, we provide evidence that these observations are applicable in vivo by demonstrating that HDAC inhibition decreased neointima formation and expression of cyclin D1 in a murine model of vascular injury. (ahajournals.org)
- Phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was found to regulate PDCD4 expression because inhibition of PI3K by LY294002 and wortmannin or of mTOR by rapamycin induced PDCD4 protein and mRNA expression. (aacrjournals.org)
- Conversely in MCF-7/ADR cells, inhibition of miR-222 resulted in increased PTEN expression and decreased p-Akt expression. (cancerindex.org)
- Taken together, these data elucidated that miR-222 mediated ADR-resistance of breast cancer cells partly through regulation of PTEN/Akt/FOXO1 signaling pathway and inhibition of miR-222 may improve the prognosis of breast cancer patients. (cancerindex.org)
- Both dominant-negative inhibition and siRNA knockdown of Cdk1 were able to restore the ability of TLS-ERG-expressing L-G cells to undergo terminal differentiation. (aacrjournals.org)
- It inhibits G 1 cyclin-CDK complexes that prevent phosphorylation of retinoblastoma protein (Rb), leading to subsequent inhibition of E2F dependent transcription of S-phase regulatory proteins ( Toyoshima and Hunter, 1994 ). (biologists.org)
- Inhibition of glycogen synthase kinase-3 by Akt-dependent phosphorylation promotes accumulation of β-catenin, which forms complexes with T-cell factor/lymphoid enhancer factor transcription factors and transcriptionally up-regulates cyclin D1, Myc, and other positive growth regulators. (aacrjournals.org)
- Indeed, evidence suggests that inhibition of Rho isoprenylation mediates many of the cholesterol-independent effects of statins not only in vascular wall cells 8 10 but also in leukocytes 11 and bone. (ahajournals.org)
- The immune system functions by maintaining an intricate balance between CD28/costimulation-mediated T cell activation and CTLA-4/immune checkpoint-mediated inhibition. (frontiersin.org)
- Several independent studies suggest that mimosine may modulate the synthesis of some proteins, which in turn may cause inhibition of DNA replication and cell cycle arrest ( 6 - 9 ). (mcponline.org)
- 5 Specific Ang II receptor antagonists can also partially inhibit neointima formation, which suggests that the inhibition of neointima formation by ACE inhibitors is, in part, because of a decreased level of Ang II. (ahajournals.org)
- The increase in local kinin accumulation may also be involved in the inhibition of neointima formation because icatibant, a bradykinin B 2 receptor antagonist, can partially block the protective effect of ACE inhibitors. (ahajournals.org)
- Rapamycin influences the cell cycle by up-regulation of p27, down-regulation of p21, and inhibition of p70 s6k phosphorylation. (aspetjournals.org)
- We also demonstrated that these effects of EGCG may be mediated through the inhibition of nuclear factor kappa B that has been associated with cell cycle regulation and cancer. (dr-rath-foundation.org)
- Concurrent with the I3C-induced growth inhibition, Northern blot and Western blot analyses demonstrated that I3C selectively abolished the expression of cyclin-dependent kinase 6 (CDK6) in a dose- and time-dependent manner. (wellnessresources.com)
- Inhibition was contact dependent and reliant on the absence of IL-2. (dcu.ie)
- These three articles describe a third way in which Akt resists G1 arrest, namely by a p27 KIP1 phosphorylation that impairs nuclear import and prevents its inhibition of cyclin-CDK complexes. (biomedcentral.com)
- More recent work indicates that the induction of cyclin D-CDK complexes results in the redistribution of CDK inhibitor p27 Kip1 from cyclin E-CDK2 complexes to cyclin D-CDK4/6 complexes, thereby triggering the kinase activity of cyclin E-CDK2 holoenzyme ( 6 ). (pnas.org)
- The newly synthesized cyclin D1 associates with and activates the cyclin-dependent kinases CDK4 and CDK6, leading to the phosphorylation of RB and the subsequent dissolution of the RB-E2F transcription factor complexes. (nih.gov)
- They exert these functions by binding to and inactivating cyclin-cyclin-dependent kinase (CDK) complexes. (pnas.org)
- CIP/KIP family proteins bind a wide range of G1/S and S-phase cyclin-CDK complexes including cyclin D-CDK4,6 and cyclin E-, A-CDK2 complexes. (wikipedia.org)
- The first evidence of this came from the observation that p27 would frequently immunoprecipitate with active cyclin D-CDK4 complexes. (wikipedia.org)
- Futhurmore, mouse embryonic fibroblasts deficient for p21 and p27 had lower levels of cyclin D1 and immunoprecipitated cyclinD-CDK complexes had no kinase activity. (wikipedia.org)
- CIP/KIP proteins can regulate transcription indirectly through stabilization of cyclinD-CDK and uninhibiting cyclin-CDK2 complexes that are crucial for Rb phosphorylation and release of the E2F transcription factor. (wikipedia.org)
- In this way my group has accumulated an extensive body of work on the 3D structure and function of protein complexes that ensure genome stability and provided new insights for the molecular understanding of signal transduction mechanisms underpinning cell division in eukaryotic organisms. (brookes.ac.uk)
- Once cells enter S phase, cyclin E is degraded and cyclin A enters into complexes with cdk2. (aacrjournals.org)
- The degradation of this protein, which is triggered by its CDK dependent phosphorylation and subsequent ubiquitination by SCF complexes, is required for the cellular transition from quiescence to the proliferative state. (genetex.com)
- CDC6 interacts specifically with the active Cyclin A/CDK2 complex in vitro and in vivo, but not with Cyclin E or Cyclin B kinase complexes. (sdbonline.org)
- We are studying the effect of these antagonists on p27, cyclin E, and cyclin D/cdk complexes. (mskcc.org)
- Taken together, our study suggests that EGCG causes an induction of G1-phase ckis, which inhibit the cyclin-cdk complexes operative in G0/G1 phase of the cell cycle thereby causing a G0/G1-phase arrest of the cell cycle, which is an irreversible process ultimately resulting in an apoptotic cell death. (dr-rath-foundation.org)
- 13 Two families of cdk inhibitors regulate cyclin/CDK complexes. (ahajournals.org)
- Upregulation of cyclin D2 and D3 in activated B-CLL cells was inhibited while the expression of cdk2, cdk4, and cyclin E remained unchanged. (biomedsearch.com)
- CDK2, in contrast, is positively regulated by cyclin E and negatively regulated by the Kips. (jneurosci.org)
- Much of this binding specificity comes from the cyclin partner for CDK2, either cyclin E or cyclin A, which is required for catalytic activity ( 19 ). (aacrjournals.org)
- however it was later discovered that CIP/KIP proteins, while inhibiting CDK2 activity, may also activate cyclin D-CDK4,6 activity by facilitating stable binding between cyclin D and CDK4,6. (wikipedia.org)
- The crystal structure of p27 in a complex with cyclinA-CDK2 was published in 1996. (wikipedia.org)
- The structure shows that p27 interacts with both cyclin A and CDK2. (wikipedia.org)
- This model is supported by the finding that expression of either wild-type or catalytically inactive CDK4 can sequester CIP/KIP proteins resulting in cyclin E-CDK2 activation. (wikipedia.org)
- p21 and p27 cleavage are known to promote apoptosis through activation of CDK2 activation. (wikipedia.org)
- Accumulation of cyclin D-dependent kinases during G 1 phase sequesters cdk2 inhibitors of the Cip/Kip family, complementing the effects of the E2F transcriptional program by facilitating cyclin E-cdk2 activation at the G 1 -S transition. (aacrjournals.org)
- INK4 proteins oppose the activities of the various cyclin D-dependent kinases, whereas Cip/Kip proteins specifically inhibit cyclin E-cdk2 and cyclin A-cdk2. (aacrjournals.org)
- Interestingly, Nodal signaling also induced nuclear export of p27 and CDK2. (biologists.org)
- In G1, CDC6 is nuclear and it relocalizes to the cytoplasm when Cyclin A/CDK2 is activated. (sdbonline.org)
- however, it is unlikely that the mutations destroy the structure of the proteins, since both mutants are capable of binding Cyclin A/CDK2. (sdbonline.org)
- CDK5 has strong homology with the mammalian Cdk2 and yeast cdc2 and is an unusual molecule in the Cyclin-dependent kinases (Cdks) protein family[ 4 ]. (jcancer.org)
- These results suggest that the two NESs of Cdc6 work cooperatively and distinctly for the cytoplasmic translocation of Cdc6 phosphorylated at S74 and S54 by cyclin A/Cdk2. (chemweb.com)
- Immunoprecipitation studies demonstrated increased association of both p21 Cip1 and p27 Kip1 with Cdk2 as well as diminished Cdk2 kinase activity after isoprenoid exposure, indicating a cell cycle-inhibitory role for p21 Cip1 and p27 Kip1 in pancreatic adenocarcinoma cells. (aspetjournals.org)
- CDK2 activation resulted from the degradation of the CDK inhibitor protein p27 kip1 , 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. (rupress.org)
- cAMP inhibits both platelet-derived growth factor-stimulated cyclin-dependent kinase (cdk) 2 and cdk4 activation through upregulation of the cdk2 inhibitor p27 Kip1 and downregulation of cyclin D1 expression, which leads to a complete arrest of the cells in phase G 1 . (ahajournals.org)
- In contrast, cGMP inhibits cyclin D1 expression, inhibits cdk4 activation, and delays platelet-derived growth factor-mediated cdk2 activation, resulting in a delay in G 1 /S transition. (ahajournals.org)
- A transient increase in p27 Kip1 in cdk2 immunoprecipitates, without changes in total cellular p27 Kip1 levels, correlates with the delay in cdk2 activation caused by cGMP. (ahajournals.org)
- 12 Cyclin D1/cdk4 and cyclin E/cdk2 are known to be required for G 1 /S transition and DNA synthesis. (ahajournals.org)
- Antibodies against cAMP-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG) were obtained from Calbiochem Corp. cdk2, cdk4, and cyclin E were purchased from Santa Cruz Biochemicals. (ahajournals.org)
- and is modulated by the enzymatic activity of cyclin-dependent kinases (CDKs). (jneurosci.org)
- Cyclin-dependent kinases (CDKs) and their cyclin partners are key players in regulating the entry into, passage through, and exit from the cell cycle ( 1 -8 ). (aacrjournals.org)
- Because of the critical role of the CDKs in the regulation of the cell cycle and the observed expression/activity pattern in most human cancers, considerable effort has been focused on the development of small molecule inhibitors ( 24 -26 ). (aacrjournals.org)
- Cdks 1, 2, 4, and 6 are the key Cdks that regulate the cell cycle, and are a target for a cancer treatment. (sigmaaldrich.com)
- Cyclin dependent kinases (CDKs) are typical serine/threonine kinases that display the 11 subdomains shared by all kinases. (sigmaaldrich.com)
- In ESCs, a biased cell cycle with a shortened G1-phase and an extended S-phase has been observed, which may be attributed to the reduced level of the cyclin-dependent kinases (CDKs) . (thefreelibrary.com)
- G1 cdks and cdk inhibitors. (aacrjournals.org)
- Thus, in T cells stimulated through PD-1, Cdks were not activated, and two critical Cdk substrates were not phosphorylated. (sciencemag.org)
- Cyclin-dependent kinases (CDKs) are essential for regulating key transitions in the cell cycle, including initiation of DNA replication, mitosis and prevention of re-replication. (sdbonline.org)
- Unlike the other Cdks, CDK5 has no known cell cycle or mitotic function and is not activated by cyclins[ 5 ]. (jcancer.org)
- 12 Under the appropriate stimulation, quiescent cells travel through the cell cycle as a consequence of the activation of specific cdks. (ahajournals.org)
Kip1 and p21 Cip13
- In addition, D-cyclins play a kinase-independent role by sequestering cell cycle inhibitors p27 Kip1 and p21 Cip1 . (pnas.org)
- Blockage of K + channels and membrane depolarization also caused accumulation of the cyclin-dependent kinase inhibitors p27 Kip1 and p21 CIP1 in OP cells. (jneurosci.org)
- Antibodies to cyclin D1 were from Upstate Biotechnology Inc. Antibodies to p27 Kip1 and p21 Cip1/Waf1 were obtained from Pierce Chemical and Santa Cruz Biochemicals. (ahajournals.org)
- The subventricular zone (SVZ) is the largest germinal layer in the adult mammalian brain and comprises stem cells, transit-amplifying progenitors, and committed neuroblasts. (jneurosci.org)
- D-type cyclins (cyclins D1, D2, and D3) are key components of cell cycle machinery in mammalian cells. (pnas.org)
- Also, signalling through the RAS effectors RASSF1, NORE1, mammalian STE20-like protein kinase 1 (MST1) and JUN N-terminal kinase (JNK) can lead to apoptotic death via the activation of caspase 3 and the pro-apoptotic proteins BCL-2-associated X protein (BAX) and BCL-2-homologous antagonist/killer 1 (BAK1). (nih.gov)
- In the postembryonic and adult mammalian auditory sensory epithelium, the organ of Corti, no hair-cell regeneration has ever been observed. (pnas.org)
- This finding may provide an important pathway for inducing hair-cell regeneration in the mammalian hearing organ. (pnas.org)
- The activation of the mammalian target of rapamycin (mTOR), a serine/threonine kinase, plays a pivotal role in the pathologic forms of hypertrophy in the kidneys [ 10 - 12 ]. (hindawi.com)
- One class of agents that are highly effective in the prevention of in-stent restenosis is the mammalian Target of Rapamycin (mTOR) inhibitors. (mdpi.com)
- Inhibitors of the mammalian Target of Rapamycin (mTOR) are highly effective at blocking intimal hyperplasia and have been used in drug-eluting stents. (mdpi.com)
- The CIP/KIP (CDK interacting protein/Kinase inhibitory protein) family is one of two families (CIP/KIP and INK4) of mammalian cyclin dependent kinase (CDK) inhibitors (CKIs) involved in regulating the cell cycle. (wikipedia.org)
- It is intriguing to reflect on this point, because many of the G 1 phase regulators that prove so important in accelerating or braking the cell cycle engine of mammalian cells are encoded by nonessential genes, whose elimination from the germ line needs not lead to deleterious effects on organismal development. (aacrjournals.org)
- Mammalian cells respond to extracellular mitogens and antiproliferative cytokines from the time that they exit mitosis ( vertical arrow at top ) until they reach the restriction point, after which they can complete the cell division cycle in the absence of extracellular growth factors. (aacrjournals.org)
- l -Mimosine, a plant amino acid, can reversibly block mammalian cells at late G 1 phase and has been found to affect translation of mRNAs of the cyclin-dependent kinase inhibitor p27, eIF3a (eIF3 p170), and ribonucleotide reductase M2. (mcponline.org)
- l -Mimosine, a plant amino acid derived from seeds of Leucaena leucocephala or Mimosa pudica , can specifically and reversibly block mammalian cells at late G 1 phase ( 1 , 2 ). (mcponline.org)
- In contrast with the ability of Cdc18p and the non-phosphorylatable mutant of Cdc18p to induce re-replication when overexpressed, no evidence is available that overexpression of CDC6 or the non-phosphorylatable mutants of CDC6 are sufficient by themselves to induce re-replication in mammalian cells. (sdbonline.org)
CDK4 and CDK61
- Mitogen-dependent, cyclin D-dependent kinases (cdk4 and cdk6) phosphorylate the retinoblastoma (Rb) tumor suppressor protein, helping to cancel its growth-inhibitory effects and enabling E2F transcription factors to activate genes required for entry into the DNA synthetic phase (S) of the cell division cycle. (aacrjournals.org)
Role of p273
- p27 is required for the normal histogenesis of the RPE, but the role of p27 in the mature RPE remains elusive. (molvis.org)
- To define the role of p27 in the maintenance and function of the RPE, we investigated the effects of p27 deletion on the responses of the RPE after photoreceptor damage. (molvis.org)
- These findings provide evidence for the role of p27 in the control of RPE responses to retinal damage. (molvis.org)
- TCR activation decreases the steady state protein levels of FLIP (FLICE-like inhibitory protein), an inhibitor of the Fas signaling pathway. (jimmunol.org)
- Studies on skeletal muscle cells have shown that, through a negative feedback mechanism, the activation of the mTOR pathway may lead to insulin resistance [ 15 ]. (hindawi.com)
- Dr. Cleary added that it might be possible to target elements further downstream in the GSK3 pathway such as p27. (medpagetoday.com)
- MiR-222 promotes drug-resistance of breast cancer cells to adriamycin via modulation of PTEN/Akt/FOXO1 pathway. (cancerindex.org)
- Disruption of "the Rb pathway" results from direct mutational inactivation of Rb function, by overexpression of cyclin D-dependent kinases, or through loss of p16 INK4a , an inhibitor of the cyclin D-dependent kinases. (aacrjournals.org)
- In addition to upregulation of genes related to antigen presentation and the MHC class I pathway, and cytotoxic effector molecules, cell-cycle-promoting genes were downregulated in the tumor on days 3 and 5 after CTL transfer. (aacrjournals.org)
- Skp2 is an essential member of the ubiquitin ligase protein degradation pathway responsive for degrading the cell cycle cyclin dependent kinase inhibitor p27. (bu.edu)
- Among the inhibitory immune mediators, the pathway consisting of the programed cell death 1 (PD-1) receptor (CD279) and its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273) plays an important role in the induction and maintenance of peripheral tolerance and for the maintenance of the stability and the integrity of T cells. (frontiersin.org)
- Therapeutic targeting of this pathway has resulted in successful enhancement of T cell immunity against viral pathogens and tumors. (frontiersin.org)
- Here, we will provide a brief overview on the properties of the components of the PD-1 pathway, the signaling events regulated by PD-1 engagement, and their consequences on the function of T effector cells. (frontiersin.org)
- The best-studied pathway for T cell costimulation includes B7-1/B7-2-CD28/CTLA-4 superfamily, which is essential for T cell activation and tolerance ( 9 - 13 ). (frontiersin.org)
- Isolated β cells of control but not clodronate-treated mice subjected to PDL had greater expression of Smad7 , which is both a transcriptional target of transforming growth factor β (TGFβ) signaling and encodes an inhibitor of this pathway, as well as greater expression of CyclinD1 and CyclinD2 , which encode cell cycle activating proteins. (sciencemag.org)
- Using these inhibitors along with commercially available inhibitors of the PI3k pathway, we are delineating which cellular phenotypes of ansamycins are attributive to which pathway. (mskcc.org)
- An example of a G-protein-dependent pathway is activation of phospholipase C with the subsequent production of inositol 1,4,5-phosphate and diacylglycerol. (asnjournals.org)
- Thus, our observations have uncovered a previously undefined antiproliferative pathway for I3C that implicates CDK6 as a target for cell cycle control in human breast cancer cells. (wellnessresources.com)
- The study indicates that cytoplasmic location of p27 KIP1 in breast tumours is a prognostic indicator and that the Akt pathway may be a good target for anti-cancer therapy. (biomedcentral.com)
- These mice express a cyclin-dependent kinase inhibitor 1B ( Cdkn1b ) cDNA under the direction of the tetracycline operator. (jax.org)
- CDKN1B, or p27, is a cell cycle inhibitor protein which acts by arresting cell division at G1. (jax.org)
- The TREP27 transgene was designed with the tetracycline operator ( tetO or tet-operator) driving expression of cyclin-dependent kinase inhibitor 1B ( Cdkn1b ) cDNA. (jax.org)
- CDKN1B, also known as cyclin-dependent kinase inhibitor 1B, belongs to the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitor proteins. (creativebiomart.net)
- TargetScans algorithm-based prediction demonstrated that CDKN1B (p27, Kip1), a cell cycle regulator, was a putative target of miR-24, and was confirmed by luciferase assay. (thefreelibrary.com)
- Immunoblotting was utilized to determine the protein level of p-extracellular signal-regulated kinase (ERK) 1/2, p-Akt, p-phosphoinositide 3-kinase (PI3K), p-Janus kinase 2 (JAK2), p-p53, and p21 Cip1 . (termedia.pl)
- PD-1 suppressed SKP2 transcription by inhibiting phosphoinositide 3-kinase-Akt and Ras-mitogen-activated and extracellular signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling. (sciencemag.org)
- Initially, the technology of restoring pluripotency in differentiated cells was developed in 1952 by R. Briggs and T.J. King who used the method of nuclear transplantation . (thefreelibrary.com)
- Beginning with this event, the era of genetic cell reprogramming without the use of nuclear transplantation has started. (thefreelibrary.com)
- The RPE in the KO retinas developed aberrant protrusions into the outer nuclear layer in response to photoreceptor damage and engulfed outer segment debris, as well as TUNEL-positive photoreceptor cells. (molvis.org)
- In the normal WT retinas, p27 was localized to the nuclei of RPE cells while nuclear and cytoplasmic p27 was detected in RPE cells undergoing EMT, suggesting a role for cytoplasmic p27 in the phenotype changes of RPE cells. (molvis.org)
- Adverse prognostic effect of obesity seems limited to patients with nuclear p27 expression, suggesting a host-tumor interaction. (aacrjournals.org)
- In neurons, the function of CDK5 as a cell cycle suppressor is independent of its kinase activity, but its nuclear localization via association with p27 (also known as KIP1)[ 11 ] and p35-mediated full assemble of the E2F1-CDK5 complex are needed[ 12 , 13 ]. (jcancer.org)
- The nuclear abundance of the cyclin-dependent kinase inhibitor 1β (also known as p27) was decreased in β cells from mice subjected to PDL, those overexpressing Smad7, or those cocultured with M2 macrophages. (sciencemag.org)
- Blockade of Akt activation by the phosphatidyl inositol 3'-kinase (PI3K) inhibitor LY294002, or transfection with the mutant p27 KIP1 -T157A, led to nuclear p27 KIP1 localisation. (biomedcentral.com)
- The best prognostic subgroup of breast tumours had strong, exclusively nuclear p27 KIP1 staining, while cancers with lower expression levels, but cytoplasmic localisation, had the worst survival rates. (biomedcentral.com)
Expression of p271
- Using cell cycle-blocking agents, we demonstrate that activated T cells arrested in G 1 phase contain high levels of FLIP protein, whereas activated T cells arrested in S phase have decreased FLIP protein levels. (jimmunol.org)
- 2013. A short G1 phase is an intrinsic determinant of naïve embryonic stem cell pluripotency. (springer.com)
- As a result, phase I and II trials of calcitriol either alone or in combination with the carboplatin, paclitaxel, or dexamethasone have been initiated in patients with androgen-dependent and -independent prostate cancer and advanced cancer. (springer.com)
- Overexpression of cyclin E drives cells into S phase ( 20 , 21 ). (aacrjournals.org)
- NSC43067 arrests the cell cycle at the G0/G1 phase at lower concentrations and at the G2/M cell cycle phase at higher concentrations. (sigmaaldrich.com)
- Transient knockdown of RhoA in FaDu cells decreased expression of Skp2, enhanced the level of Cip/Kip CDKIs, and attenuated S-phase entry. (garvan.org.au)
- Proteasome inhibitors such as PS-341, a dipeptide boronic acid analogue, represent an interesting new class of potential anticancer drugs, which are entering early-phase clinical trials. (aacrjournals.org)
- Three days after CTL transfer, we observed diffuse infiltration of CTLs into the tumor with a large number of tumor cells arrested at the G 1 phase of the cell cycle, and the presence of spotty apoptotic or necrotic areas. (aacrjournals.org)
- Furthermore, in C2, the cyclin-dependent kinase inhibitor (p27 KIP1 ) was much more abundant than in pC, and the cell cycle was arrested at the G1 phase. (ahajournals.org)
- These events induced additional inhibitory checkpoints in the cell cycle by increasing the abundance of the G 1 phase inhibitor p15 INK4 and repressing the Cdk-activating phosphatase Cdc25A. (sciencemag.org)
- This reduction was clearly linked to cell cycle blockade, occurring at G2/M phase. (sigmaaldrich.com)
- In yeast, CDK activity is required both for entry into S phase of the cell cycle and for restricting replication to 'once and only once' per cell cycle. (sdbonline.org)
- Furthermore, work is in progress to identify functional targets of src kinases at the G2-M phase of the cell cycle. (mskcc.org)
- E7 oncoprotein binds to pRb tumor-suppressor family[ 5 , 6 ], and interacts with transcription factor EZH2, a member of the Polycomb Repressive Complex 2 (PRC2) that involves in S phase of cell cycle[ 7 ]. (jcancer.org)
- an inhibitor of the D cyclins, which are the rate-limiting effectors of the G1-S phase transition ( Ohtsubo and Roberts, 1993 ). (elifesciences.org)
- Indeed, overexpression of D-cyclins is seen in a large number of human cancers ( 2 , 3 ). (pnas.org)
- Low energy and unadjusted fat intakes were associated with cyclin D 1 overexpression ( P = 0.02 and 0.007, respectively), whereas cyclin E overexpression was positively correlated with fat intake. (biomedcentral.com)
- Immunofluorescence labeling was used to measure the cell surface area, and 3H-leucine incorporation was used to detect the synthesis of total protein in neonatal rat cardiac myocytes (NRCMs) with the overexpression of miR-24. (thefreelibrary.com)
- Our results provide genetic evidence that p27 Kip1 functions downstream of cyclin D1. (pnas.org)
- In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI) for EGFR downstream signaling is initially effective. (mdpi.com)
- However, the transcriptional mechanisms downstream of FoxM1 that control these cell cycle events remain to be determined. (jax.org)
- Targeting cyclin D1, a downstream effector of INI1/hSNF5, in rhabdoid tumors. (springer.com)
Inhibit cell cycle2
- The data indicate that p27 KIP1 normally acts as a tumour suppressor protein, but that the oncogenic activation of Akt leads to mislocation of p27 KIP1 to the cytoplasm where it is unable to inhibit cell cycle proteins. (biomedcentral.com)
- One mechanism involves changing the level of a factor beyond a threshold at which it can stimulate or inhibit cell cycle entry. (elifesciences.org)
Cip1 and p27 Kip12
- When siRNA was used to inhibit expression of p21 Cip1 and p27 Kip1 proteins in MIA PaCa-2 cells, conditional resistance to all three isoprenoid compounds was evident. (aspetjournals.org)
- Given similar findings in this cell line and in BxPC-3 human pancreatic adenocarcinoma cells, we conclude that the chemotherapeutic isoprenoid compounds perillyl alcohol, farnesol, and geraniol invoke a p21 Cip1 - and p27 Kip1 -dependent antiproliferative mechanism in human pancreatic adenocarcinoma cells. (aspetjournals.org)
- The relevance of this molecular mechanism in controlling peripheral T cell homeostasis is highlighted by the fact that mutations in Fas or FasL result in deficient AICD responses, and hence in autoimmune and lymphoproliferative-like diseases ( 9 , 10 , 11 , 12 , 13 ). (jimmunol.org)
- The molecular mechanism by which Fas/FasL interactions control AICD of peripheral T cells is poorly understood. (jimmunol.org)
- In particular, a class of cell cycle inhibitory proteins has been cloned and characterized but details of the molecular mechanism of their action have yet to be resolved. (semanticscholar.org)
- We examined the mechanism of the antiproliferative effect of retinoids on human coronary artery smooth muscle cells (human CASMCs). (semanticscholar.org)
- Liver regeneration is a mechanism by which hepatic cells compensate for the loss of liver mass. (springer.com)
- PI3Ks are also activated by receptor kinases through a second mechanism involving binding of p110 to Ras. (aacrjournals.org)
- In particular, we recently established that the AGR2 protein serves an essential role in EGFR presentation to the cell surface, and represents a novel mechanism of regulating cell signaling. (stanford.edu)
- We highlight the evidence suggesting that polyphenolic compounds have a dose and disorder dependent effects in improving neurological dysfunctions, and so their mechanism of action could stimulate the UPS, induce the protein degradation or inhibit UPS and reduce protein degradation. (frontiersin.org)
- Although central tolerance mechanism results in the removal of the most of the autoreactive T cells during thymic selection, a fraction of self-reactive lymphocytes escapes to the periphery and pose a threat to cause autoimmunity. (frontiersin.org)
- To identify a potential mechanism by which PI3K could exert its proliferative and antiapoptotic effects, we focused on cyclin-dependent kinase (CDK) inhibitor p27 KIP1 . (asm.org)
- In this study, we investigated isoprenoid effects on the cell cycle and observed a similar antiproliferative mechanism of action among the three compounds. (aspetjournals.org)
- We are currently assessing the mechanism of its antiproliferative activity and effects on cell cycle. (mskcc.org)
- To further elucidate the mechanism of this promising synergy between NBT and ATST, herein, we measured the levels of NBT, its major metabolites and ATST in the colonic tissue of rats fed NBT (0.05% w/w, in diet) + ATST (0.02% w/w, in diet), and determined the mode of interaction between the major NBT metabolite and ATST in inhibiting colon cancer cell growth. (rsc.org)
- Our results demonstrated a strong synergy produced by the 4DN/ATST co-treatment in inhibiting colon cancer cell growth, which provided a novel mechanism by which NBT/ATST in combination synergistically inhibit colon carcinogenesis. (rsc.org)
- In conclusion, this study showed the expression profiles of circRNAs regulated by HPV16 E7 in cervical cancer cells and provides novel insights into the new potential candidates for future mechanism studies. (jcancer.org)
- Take the example of α-catenin: first identified as a cytoplasmic protein that binds indirectly to classical cadherin cell adhesion molecules, its function and mechanism(s) of action have long been defined in terms of this interaction. (biologists.org)
- In this study, our aim was to delineate the molecular mechanism underlying cAMP and cGMP suppression of cell cycle transition in human SMCs. (ahajournals.org)
- Thus melanoma cells remain sensitive to negative growth regulatory signals originating from fibrillar collagen, and the proteolytic degradation of fibrils is a mechanism allowing tumor cells to escape these restrictive signals. (jove.com)
Degradation of p272
- Moreover, upregulation of miR-222 expression in MCF-7/S cells is associated with decreased PTEN expression levels and increased phospho-Akt (p-Akt) expression. (cancerindex.org)
- Low RhoH levels on the other hand led to an upregulation of IL3-dependent cell growth, STAT5 activity and an increase of CD123 surface expression, linking RhoH to a CD123/STAT5 phenotype that has been described in AML patients. (pubmedcentralcanada.ca)
- Zhou et al demonstrated that downregulation of lncRNA MEG3 mediated by DNMT3b contributed to nickel malignant transformation of human bronchial epithelial cells via modulating PHLPP1 transcription and HIF -1α translation ( 11 ). (spandidos-publications.com)
- Notably, normal colon cells and keratinocytes were less susceptible to combo-induced cell death and EGFR downregulation. (sigmaaldrich.com)
- In this study, undifferentiated human monocytoid U937-1 cells were used as a model of normal monocytes and analysed regarding accumulation of boronophenylalanine (BPA) in vitro . (diva-portal.org)
- B cell chronic lymphocytic leukemia (B-CLL) is characterized by malignant accumulation of small CD5 positive lymphocytes in the peripheral blood. (tum.de)
- b ), with type B cells being the primary precursors (stem cells) that generate migratory neuroblasts via the highly proliferative transit-amplifying progenitor (type C cell). (jneurosci.org)
- Disruptions in the number of CNS progenitor cells result in malformations that seriously impair or eliminate CNS function ( Walsh, 1999 ). (biologists.org)
- 1990 ) Ion channel expression by white matter glia: the O-2A glial progenitor cell. (biologists.org)
- In addition to the iPSC technology, the first reports about the possibility for direct transdifferentiation of somatic cells (including those of mesodermal origin) into neural stem/progenitor cells have appeared [5, (thefreelibrary.com)
- However, both polarising region and oligodendrocyte progenitor cells require permissive signals to maintain them in a proliferative state. (elifesciences.org)
- In addition, both polarising region and oligodendrocyte progenitor cells require an instructive hydrophobic signal. (elifesciences.org)
- A large number of studies have reported that p27 expression is frequently downregulated in human tumors. (nih.gov)
- It then became evident that the majority of these tumors are derived from lymphoid cells of T or null immunophenotype. (bloodjournal.org)
- This" multicellular resistance" reflects the relative intrinsic drug-resistant phenotype of most solid tumors growing in vivo and is due to factors such as limited drug penetration or reduced fractions of proliferating cells. (aacrjournals.org)
- Among 630 colon cancers (stage I-IV) in two prospective cohort studies, we detected p27 alterations (cytoplasmic p27 localization or p27 loss) in 500 tumors (79%) by immunohistochemistry. (aacrjournals.org)
- The remaining 130 (21%) tumors were "p27-nuclear+. (aacrjournals.org)
- Src kinase activity is elevated in some human tumors, including breast and colon cancer. (mskcc.org)
- Amplification of the HER family of tyrosine kinases occurs in a subset of tumors. (mskcc.org)
- We are studying the basis for the sensitivity of some tumors to these inhibitors. (mskcc.org)
- Description - Mast cell tumors (MCTs) or mastocytomas are the most common cutaneous tumor found in dogs. (wearethecure.org)
- Mast cell tumors have been classified according to their degree of proliferativeness. (wearethecure.org)
- Most mast cell tumors belong to Grade I. (wearethecure.org)
- Mast cell tumors should be staged because it gives us an idea abou how they have metatasized in the body. (wearethecure.org)
- Of the 63 tumors evaluated 23 [36.5%] were positive for p27 within the nucleus. (biomedcentral.com)
- These kinases phosphorylate Y449 on the IL-7Rα intracellular domain, creating a docking site for Stat5 ( 17 , 18 ) and the p85 subunit of PI3K ( 19 ). (jimmunol.org)
- Wild type and constitutively active Akt were both shown to phosphorylate p27 KIP1 at threonine157, leading to cytoplasmic localisation of p27 KIP1 . (biomedcentral.com)
- Cell fate determination by transcription factors. (springer.com)
- Reverse transcription-quantitative polymerase chain reaction was performed to determine the level of SNHG5 in the BC tissues and cell lines. (spandidos-publications.com)
- IL-3 was found to repress the expression of the cyclin-dependent kinase inhibitor p27 KIP1 through activation of PI3K, and this occurs at the level of transcription. (asm.org)
- Ligand-activated VDR competed with T cell transcription factor (TCF)-4 for β-catenin binding. (rupress.org)
- S transition in vascular smooth muscle cells. (semanticscholar.org)
- 1 9 Indeed, Rho-associated protein kinase increases the sensitivity of vascular smooth muscle to calcium in hypertension 13 and coronary spasm. (ahajournals.org)
- LAM cells show strong reactivity (A). Pulmonary vascular smooth muscle cells are also strongly positive (arrow). (atlasgeneticsoncology.org)
- However, its effect on vascular smooth muscle cells (VSMCs) is poorly understood. (ahajournals.org)
- Dysregulated growth and motility of vascular smooth muscle cells (VSMCs) contribute to neointimal lesion development during the pathogenesis of vascular obstructive disease, including atherosclerosis, restenosis after percutaneous interventions, and bypass graft stenosis. (ahajournals.org)
- Vascular smooth muscle cells (SMCs) in the normal arterial media are quiescent, contractile, and resistant to growth factor stimuli. (ahajournals.org)
Tyrosine kinase in1
- The differential selectivity of the pro-apoptotic effects of alpha-lipoic acid for transformed cells supports its potential use in the treatment of neoplastic disorders. (nih.gov)
- In combination with calcitriol, dexamethasone results in a significant time- and dose-dependent increase in VDR protein and an enhanced apoptotic response as compared to calcitriol alone. (springer.com)
- PS-341 induced apoptotic cell death in carcinoma cells in both culture systems. (aacrjournals.org)
- IL-7 is required for early T cell development in the thymus, mainly to protect cells at the double-negative (DN 3 ) 2 and DN3 stages from apoptotic cell death ( 4 ). (jimmunol.org)
- Here we investigated the effect of metformin and rapamycin on mTOR-related phenotypes in cell lines of epithelial origin. (hindawi.com)
- Treatment of nonneoplastic human prostate epithelial cells (PWR-1E) with berberine under identical conditions did not significantly affect their viability. (aacrjournals.org)
- The effectiveness of berberine in checking the growth of androgen-insensitive, as well as androgen-sensitive, prostate cancer cells without affecting the growth of normal prostate epithelial cells indicates that it may be a promising candidate for prostate cancer therapy. (aacrjournals.org)
- B to E, dose- and time-dependent effect of berberine on the viability of human prostate carcinoma cells and nonneoplastic human prostate epithelial (PWR-1E) cells. (aacrjournals.org)
- Higher-magnification view of tissue shown in C. A strong granular reaction is present in large epithelioid LAM cells adjacent to epithelial cells covering LAM lung nodules (arrow) (D) (original magnification x1000). (atlasgeneticsoncology.org)
- In addition, WT RPE cells exhibited evidence of the epithelial-mesenchymal transition (EMT), including morphological changes, induction of α-smooth muscle actin expression, and attenuated expression of tight junction protein ZO-1 while these changes were absent in the KO retinas. (molvis.org)
- Volume fractions of connective tissue, bile duct epithelial, and desmin- and actin-positive cells were lower in BDL SIR than in BDL CTR rats. (aspetjournals.org)
- In a number of cell lines (including HeLa cells, U-2 OS osteosarcoma cells and Hs 578Bst breast epithelial cells), ectopic expression of cyclin A increases hormone-dependent and hormone-independent transcriptional activation by the estrogen receptor. (sdbonline.org)
- β-Catenin is a protooncogene encoding a cytoskeleton-associated protein, which in normal epithelial cells is bound mostly to the cytoplasmic tail of E-cadherin at the adherens junctions (for review see Morin, 1999 ). (rupress.org)
- Type 2 mutations demonstrated an epithelial morphology similar to wild-type VHL in the majority of the renal cell lines used. (biomedcentral.com)
- Knockdown of p27 in cells with wild-type VHL led to perturbations of both epithelial morphology and ZO-1 localization to tight junctions. (biomedcentral.com)
- We found that Nodal increased p27 mRNA and protein levels by enhancing their stability. (biologists.org)
- Liver protein levels of p27, p21, p70 S6 kinase (p70 s6k ), phosphorylated p70 s6k ( p -p70 s6k ), eukaryotic initiation factor 4E-binding protein (4E-BP1), p -4E-BP1 (Thr37/46), and p -4E-BP1 (Ser65/Thr70) were determined by Western blotting. (aspetjournals.org)
- 2010. A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity. (springer.com)
- However, the first truly pluripotent cells were the embryonic stem cells isolated in 1981 by two independent groups from early murine embryos . (thefreelibrary.com)
- Truly, pluripotent cells are embryonic stem cells (ESCs) derived from the internal cell mass in blastocysts. (thefreelibrary.com)
- Early embryonic cell cycles exhibit rapidly alternating S and M phases without gap phases between them. (aacrjournals.org)