A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
A 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.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
A 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.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
A 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.
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.
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.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.
A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.
A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.
A 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.
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.
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.
A cell line derived from cultured tumor cells.
Agents that inhibit PROTEIN KINASES.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.
A 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.
A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.
A cyclin subtype that 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.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION.
A 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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.
Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.
Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
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.
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.
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.
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.
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.
A cyclin D subtype which is regulated by GATA4 TRANSCRIPTION FACTOR. Experiments using KNOCKOUT MICE suggest a role for cyclin D2 in granulosa cell proliferation and gonadal development.
Cells 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.
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.
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.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
The 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.
Established cell cultures that have the potential to propagate indefinitely.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
A 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.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.
An INK4 cyclin-dependent kinase inhibitor containing four ANKYRIN-LIKE REPEATS. INK4B is often inactivated by deletions, mutations, or hypermethylation in HEMATOLOGIC NEOPLASMS.
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.
A cyclin G subtype that is constitutively expressed throughout the cell cycle. Cyclin G1 is considered a major transcriptional target of TUMOR SUPPRESSOR PROTEIN P53 and is highly induced in response to DNA damage.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.
A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.
RNA 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.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
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)
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN REPEATS. Aberrant expression of this protein has been associated with TESTICULAR CANCER.
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.
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.
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.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
The 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.
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.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
A 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).
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.
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.
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.
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.
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.
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.
Elements of limited time intervals, contributing to particular results or situations.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
A 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.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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.
BENZOIC ACID amides.
The rate dynamics in chemical or physical systems.
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.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A cyclin B subtype that colocalizes with GOLGI APPARATUS during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A group of phenyl benzopyrans named for having structures like FLAVONES.

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

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

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

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

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

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

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

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

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

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

Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (6/4670)

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

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

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

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

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

(KudoZ) English to Bosnian translation of EURO parity CIP : (cijene...) u EUR na paritetu CIP... [Finance (general) (Bus/Financial)].
Fingerprint Dive into the research topics of The cyclin-dependent kinase inhibitor p21,sup,WAF1/Cip1,/sup, is an antiestrogen-regulated inhibitor of Cdk4 in human breast cancer cells. Together they form a unique fingerprint. ...
Anti-HER2 antibody trastuzumab is emerging as a frontline therapy for patients with metastatic breast cancers that overexpress HER2. Understanding the molecular mechanisms by which the antibody inhibits tumor growth should permit the design of even more effective trastuzumab-based protocols. Several …
Our research line is made of three sublines, specialized in the investigation of brain pathologies, including cerebrovascular diseases, neurodegenerative diseases, and brain ageing.. ...
2017) Keywords: Biomarkers, Tumor Carcinoma, Squamous Cell Cell Transformation, Viral Cyclin-Dependent Kinase Inhibitor p16 DNA, Viral Humans In Situ Hybridization Neoplasm Proteins Oncogene Proteins, .... ...
Chronic lymphocytic leukemia (CLL) cells multiply and become more resistant to immunochemotherapy in proliferation centers within tissues, whereas apoptosis occurs in the periphery. Various models recapitulate these microenvironments in vitro, such as stimulation with CD154 and IL4. Using this system, we observed a 30- to 40-fold induction of wild-type p53 protein in 50 distinct human CLL specimens tested, without the induction of either cell-cycle arrest or apoptosis. In contrast, the mRNA levels for p53 did not increase, indicating that its elevation occurred posttranscriptionally. Mechanistic investigations revealed that under the conditions studied, p53 was phosphorylated on residues associated with p53 activation and increased half-life. However, p53 protein induced in this manner could transcriptionally activate only a subset of target genes. The addition of a DNA-damaging agent further upregulated p53 protein levels, which led to apoptosis. p53 induction relied on the increase in ...
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Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
Folia Histochemica et Cytobiologica (FHC) is an international,English-language journal devoted to the developing fields of histochemistry,cytochemistry,cell biology,cell and tissue biology.It is source of the recent research in fields of and cell biology
Disruption of the cyclin-dependent kinase-inhibitory domain of p27 enhances growth of mice. Growth is attributed to an increase in cell number, due to increased cell proliferation, most obviously in tissues that ordinarily express p27 at the highest levels. Disruption of p27 function leads to nodula …
BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells ...
Harrison, T.A., Smith Adams, L.B., Moore, P.D., Perna, M.K., Sword, J.D.and Defoe, D. M.. Accelerated turnover of taste bud cells in mice deficient for the cyclin-dependent kinase inhibitor p27Kip1.BMC Neuroscience 2011, 12:34 ...
Results: In vitro studies showed a pronounced growth inhibitory and pro-apoptotic effect of LBH589 on both HCC cell lines at low micromolar concentrations (IC50 approx. 0.1 µM). Interstingly, the pro-apoptotic effect of Panobinostat was not paralleled by a breakdown of ΔΨm. p53wt HepG2 cells were more sensitive than the p53-/- Hep3B cells. Quantitative PCR and western blotting showed an involvement of the cell cycle regulators p21cip1/waf1 and Chek1 but not the bax/bcl-2 system. Panobinostat regulated the expression of p21cip1/waf1 via a transcriptional upregulation as evidenced by ChIP ...
The KOMP Repository Collection is located at the MMRRC at the University of California, Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
Due to its role in aging and antitumor defense, cellular senescence has recently attracted increasing interest. However, [the] detection of senescent cells remains difficult due to the lack of specific biomarkers. ndeed, most determinants of cellular senescence, such as the upregulation of p53, p16Ink4a, p21WAF/CIP1 or SASP-associated cytokines, are not exclusively observed in senescence, but can also occur in other types of stress responses. In addition, alterations like SAHF or DNA-SCARS formation are frequently observed, but not necessarily a mandatory feature or exclusive to senescent cells. The current gold standard for the detection of senescence is the so-called senescence-associated β-galactosidase (SA-β-Gal) activity. Although SA-β-Gal has been first suggested as a distinct enzyme, its activity is derived from lysosomal β-Gal encoded by the GLB1 gene. β-Gal is an accepted marker of senescence, but its reliability and specificity have been questioned, as a positive β-Gal reaction ...
1OIT: Imidazo[1,2-A]Pyridines: A Potent and Selective Class of Cyclin-Dependent Kinase Inhibitors Identified Through Structure-Based Hybridisation
Complete information for CDKN2D gene (Protein Coding), Cyclin Dependent Kinase Inhibitor 2D, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for CDKN2B gene (Protein Coding), Cyclin Dependent Kinase Inhibitor 2B, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
1E1X: Identification of Novel Purine and Pyrimidine Cyclin-Dependent Kinase Inhibitors with Distinct Molecular Interactions and Tumor Cell Growth Inhibition Profiles.
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Despite its potential role as a tumor suppressor, p27 gene, a member of the Cip/Kip family of cyclin-dependent kinase inhibitor genes, has never been found mutated in human tumors. We investigated p27 protein expression in a series of 108 non-small cell lung cancers (57.4% stage 1, 16.7% stage 2, and 25.9% stage 3) to determine whether the lack or altered expression of this protein correlates with neoplastic transformation and/or progression. We performed immunohistochemistry and Western blot analysis of each specimen. We found that tumors expressing low to undetectable levels of p27 contained high p27 degradation activity. When we evaluated the outcome of the patients in relationship to p27 expression, we found p27 to be a prognostic factor correlating with the overall survival times (P = 0.0012).. The possibility of a simple assay, such as the immunohistochemical analysis of p27 expression on routinely formalin-fixed, paraffin-embedded specimens, has considerable value for the prognosis of ...
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The major findings in this study are that the Kip/Cip and Ink CKIs differentially regulate cdk2 and cdk4 in VSMCs; this, in turn, leads to differences in the inhibition of VSMC proliferation in vitro and in vivo. The expression of p27Kip1 and p21Cip1 in VSMCs inactivated cdk2 and cdk4, whereas p16Ink4 inhibited only cdk4 activity. In vivo, p27Kip1 significantly inhibited intimal cell proliferation and the development of a neointima after vascular injury, whereas p16Ink4 expression did not lead to a reduction in cell proliferation or neointima formation.. This different pattern of CKI inactivation of the CDKs suggests varied biological roles for p27Kip1 and p21Cip1 compared with p16Ink4 in VSMCs. p27Kip1 was initially characterized as an inhibitor of cyclin E/cdk2 phosphorylation.10 11 p27Kip1 and p21Cip1 are upregulated in several animal models of wound repair. p27Kip1 is constitutively expressed in normal arteries, is downregulated after arterial injury, and is upregulated during the later ...
cGMP Dependent Kinase Inhibitor Peptide chemical properties, What are the chemical properties of cGMP Dependent Kinase Inhibitor Peptide 82801-73-8, What are the physical properties of cGMP Dependent Kinase Inhibitor Peptide ect.
Mammalian taste buds contain several specialized cell types that coordinately respond to tastants and communicate with sensory nerves. While it has long been appreciated that these cells undergo continual turnover, little is known concerning how adeq
Cellular senescence is a cell cycle arrest accompanied by high expression of cyclin dependent kinase inhibitors which counteract overactive growth signals, which serves as a tumor suppressive mechanism. Senescence can be a result of telomere shortening (natural or replicative senescence) or DNA damage resulting from exogenous stressors (induced senescence). Here, we performed gene expression profiling through RNA-seq of replicative senescence, adriamycin-induced senescence, H2O2-induced...
Transforming growth factor-β (TGF-β) plays an important role in regulating hematopoiesis, inhibiting proliferation while stimulating differentiation when appropriate. We previously demonstrated that the type III TGF-β receptor (TβRIII, or betaglycan) serves as a novel suppressor of cancer progression in epithelial tumors; however, its role in hematologic malignancies is unknown. Here we demonstrate that TβRIII protein expression is decreased or lost in the majority of human multiple myeloma specimens. Functionally, restoring TβRIII expression in myeloma cells significantly inhibited cell growth, proliferation, and motility, largely independent of its ligand presentation role. In a reciprocal fashion, shRNA-mediated silencing of endogenous TβRIII expression enhanced cell growth, proliferation, and motility. Although apoptosis was not affected, TβRIII inhibited proliferation through induction of the cyclin-dependent kinase inhibitors p21 and p27. TβRIII further regulated myeloma cell ...
The p57(Kip2) cyclin-dependent kinase inhibitor (CDKi) has been implicated in embryogenesis, stem-cell senescence and pathologies, but little is known of its role in cell cycle control. Here, we show that p57(Kip2) is ...
p21 Waf1/Cip1/CDKN1A抗体(F-8)是单克隆抗-p21 Waf1/Cip1抗体,用于WB, IP, IF和ELISA检测小鼠、大鼠和人p21 Waf1/Cip1。被31篇文献引用
CDKN2A / p14ARF antibody (cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)) for ICC/IF, IHC, IHC-Fr, IHC-P, WB. Anti-CDKN2A / p14ARF pAb (GTX23642) is tested in Human samples. 100% Ab-Assurance.
Effects of exogenous p62-overexpression. (a) H23 cells were transfected with indicated siRNAs for 3 days. After transfection, cell viability was measured, and
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This Histri was built automatically but not manually verified. As a consequence, the Histri can be incomplete or can contain errors ...
This Histri was built automatically but not manually verified. As a consequence, the Histri can be incomplete or can contain errors ...
The cortactin oncoprotein is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC), often due to amplification of the encoding gene (CTTN). While cortactin overexpression enhances invasive potential, recent research indicates that it also promotes cell proliferation, but how cortactin regulates the cell cycle machinery is unclear. In this article we report that stable short hairpin RNA-mediated cortactin knockdown in the 11q13-amplified cell line FaDu led to increased expression of the Cip/Kip cyclin-dependent kinase inhibitors (CDKIs) p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) and inhibition of S-phase entry. These effects were associated with increased binding of p21(WAF1/Cip1) and p27(Kip1) to cyclin D1- and E1-containing complexes and decreased retinoblastoma protein phosphorylation. Cortactin regulated expression of p21(WAF1/Cip1) and p27(Kip1) at the transcriptional and posttranscriptional levels, respectively. The direct roles of p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) ...
TBX3, a member of the T-box family of transcription factors, is essential in development and has emerged as an important player in the oncogenic process. TBX3 is overexpressed in several cancers and has been shown to contribute directly to tumour formation, migration and invasion. However, little is known about the molecular basis for its role in development and oncogenesis because there is a paucity of information regarding its target genes. The cyclin-dependent kinase inhibitor p21WAF1 plays a pivotal role in a myriad of processes including cell cycle arrest, senescence and apoptosis and here we provide a detailed mechanism to show that it is a direct and biologically relevant target of TBX3. Using a combination of luciferase reporter gene assays and in vitro and in vivo binding assays we show that TBX3 directly represses the p21WAF1 promoter by binding a T-element close to its initiator. Furthermore, we show that the TBX3 DNA binding domain is required for the transcriptional repression of p21WAF1
https://www.databridgemarketresearch.com/toc/?dbmr=global-cell-cycle-inhibitors-market. Competitive Landscape and Global Cell Cycle Inhibitors Market Share Analysis. Cell cycle inhibitors market competitive landscape provides details by competitor. Details included are company overview, company financials, revenue generated, market potential, investment in research and development, new market initiatives, global presence, production sites and facilities, company strengths and weaknesses, product launch, clinical trials pipelines, product approvals, patents, product width and breath, application dominance, technology lifeline curve. The above data points provided are only related to the companies focus related to cell cycle inhibitors market.. Global Cell Cycle Inhibitors Market Country Level Analysis. The countries covered in the cell cycle inhibitors market report are U.S., Canada, Mexico in North America, Brazil, Argentina, Peru, Rest of South America, as part of South America, Germany, ...
Background Over the last decade a number of species, from farm animals to rodents, have been cloned using somatic cell nuclear transfer technology (SCNT). This technique has the potential to revolutionize the way that genetically modified animals are made. In its current state, the process of SCNT is very inefficient (|5% success rate), with several technical and biological hurdles hindering development. Yet, SCNT provides investigators with powerful advantages over other approaches, such as allowing for prescreening for the desired level of transgene expression and eliminating the excess production of undesirable wild-type animals. The rat plays a significant role in biomedical research, but SCNT has been problematic for this species. In this study, we address one aspect of the problem by evaluating methods of activation in artificially constructed rat embryos. Principal Findings We demonstrate that treatment with a calcium ionophore (ionomycin) combined with a variety of cyclin-dependent kinase
The Notch family of transmembrane receptors regulates both cell fate decisions and the maintenance of adult stem cells, processes that require precise control of the cell cycle. Although Notch1 activation had previously been shown to alter the cell cycle in hematopoietic progenitor cells and to delay their commitment to the myeloid lineage, a direct link between Notch1 and cell cycle control pathways had not been established in these cells.. Sarmento et al. now find the link and show that constitutive Notch1 activation drives cell cycling by increasing the activity of cyclin-dependent kinase-2 (CDK2), a protein that promotes progression into the S phase of the cell cycle. CDK2 activation resulted from the degradation of the CDK inhibitor protein p27kip1, which was triggered by the Notch1-induced expression of a protein called SKP2-a component of a ubiquitin ligase complex that targets proteins for proteosomal degradation.. How Notch-induced changes in cell cycle kinetics influence ...
To confirm that the accumulation of p53 was due to decreased degradation of the protein rather than elevated expression of the p53 gene, we treated three wild-type p53 cancer cell lines with Nutlin-1 for 8 hours and monitored the expression of the p53 and p21 genes by real-time polymerase chain reaction (PCR) (Fig. 2B). The transcription of p21 increased in a dose-dependent manner in all cell lines consistent with accumulation of its transcriptional activator p53 (Fig. 2A). By contrast, transcription of the p53 gene itself was unaffected by Nutlin-1, even at the highest concentration tested (16 μM), which caused an 8- to 10-fold induction of p21 mRNA. These data indicate that the Nutlins up-regulate p53 by means of a posttranslational mechanism.. One of the main cellular consequences of p53 activation in proliferating cells is cell cycle arrest in G1 and G2 phases. The cyclin-dependent kinase inhibitor p21 plays a major role in this arrest (22). Cell cycle analysis of bromodeoxyuridine ...
Substituted guanines and pyrimidines were tested as inhibitors of cyclin B1/CDK1 and cyclin A3/CDK2 and soaked into crystals of monomeric CDK2. O6-Cyclohexylmethylguanine (NU2058) was a competitive inhibitor of CDK1 and CDK2 with respect to ATP (Ki values: CDK1, 5 +/- 1 microM; CDK2, 12 +/- 3 microM) and formed a triplet of hydrogen bonds (i.e., NH-9 to Glu 81, N-3 to Leu 83, and 2-NH2 to Leu 83). The triplet of hydrogen bonding and CDK inhibition was reproduced by 2,6-diamino-4-cyclohexylmethyloxy-5-nitrosopyrimidine (NU6027, Ki values: CDK1, 2.5 +/- 0.4 microM; CDK2, 1.3 +/- 0.2 microM). Against human tumor cells, NU2058 and NU6027 were growth inhibitory in vitro (mean GI50 values of 13 +/- 7 microM and 10 +/- 6 microM, respectively), with a pattern of sensitivity distinct from flavopiridol and olomoucine. These CDK inhibition and chemosensitivity data indicate that the distinct mode of binding of NU2058 and NU6027 has direct consequences for enzyme and cell growth inhibition.
Recombinant human CDKN1B protein, fused to His-tag at N-terminus, was expressed in E. coli and purified by using conventional chromatography. MW: 24.2 kDa.
Looking for exogenous p? Find out information about exogenous p. A group of substances thought to be polysaccharides of microbial origin that produce an increase in body temperature when injected into humans and some animals Explanation of exogenous p
Melanoma resistant to MAPK inhibitors (MAPKi) displays loss of fitness upon experimental MAPKi withdrawal and, clinically, may be resensitized to MAPKi therapy after a drug holiday. Here, we uncovered and therapeutically exploited the mechanisms of MAPKi addiction in MAPKi-resistant BRAFMUT or NRASMUT melanoma. MAPKi-addiction phenotypes evident upon drug withdrawal spanned transient cell-cycle slowdown to cell-death responses, the latter of which required a robust phosphorylated ERK (pERK) rebound. Generally, drug withdrawal-induced pERK rebound upregulated p38-FRA1-JUNB-CDKN1A and downregulated proliferation, but only a robust pERK rebound resulted in DNA damage and parthanatos-related cell death. Importantly, pharmacologically impairing DNA damage repair during MAPKi withdrawal augmented MAPKi addiction across the board by converting a cell-cycle deceleration to a caspase-dependent cell-death response or by furthering parthanatos-related cell death. Specifically in MEKi-resistant NRASMUT or ...
CDKN1A - CDKN1A (untagged)-Human cyclin-dependent kinase inhibitor 1A (p21, Cip1) (CDKN1A), transcript variant 2 available for purchase from OriGene - Your Gene Company.
CDKN2A - CDKN2A (untagged)-Human cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) (CDKN2A), transcript variant 4 available for purchase from OriGene - Your Gene Company.
Raje N, Hideshima T, Mukherjee S, Raab M, Vallet S, Chhetri S, Cirstea D, Pozzi S, Mitsiades C, Rooney M, Kiziltepe T, Podar K, Okawa Y, Ikeda H, Carrasco R, Richardson PG, Chauhan D, Munshi NC, Sharma S, Parikh H, Chabner B, Scadden D, Anderson KC. Preclinical activity of P276-00, a novel small-molecule cyclin-dependent kinase inhibitor in the therapy of multiple myeloma. Leukemia. 2009 May; 23(5):961-70 ...
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Cyclin-dependent kinase inhibitor 1A (p21, Cip1). Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human ... cyclin-dependent protein serine/threonine kinase inhibitor activity. • protein binding. • cyclin-dependent protein kinase ... PCNA-p21 complex. Biological process. • regulation of cyclin-dependent protein serine/threonine kinase activity. • G1/S ... cyclin-dependent protein kinase holoenzyme complex. • nucleus. • nucleoplasm. • cytosol. • intracellular membrane-bounded ...
The cyclin-dependent kinase inhibitor p21 is induced by both p53-dependent and p53-independent mechanisms and can arrest the ... ISBN 978-1-58829-500-2.[page needed] Gartel AL, Tyner AL (June 2002). "The role of the cyclin-dependent kinase inhibitor p21 in ... cell cycle at the G1/S and G2/M checkpoints by deactivating cyclin/cyclin-dependent kinase complexes. The SOS response is the ... In one of the earliest steps, the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), phosphorylates SIRT6 on ...
... cyclin-dependent kinase inhibitor". Cancer Research. 64 (5): 1669-74. doi:10.1158/0008-5472.can-03-3286. PMID 14996726. ... Prince S, Carreira S, Vance KW, Abrahams A, Goding CR (March 2004). "Tbx2 directly represses the expression of the p21(WAF1) ... It is known that Tbx2 functions in a dose-dependent manner; therefore, duplication or deletion of the region encompassing Tbx2 ... "T-box 2 represses NDRG1 through an EGR1-dependent mechanism to drive the proliferation of breast cancer cells". Oncogene. 29 ( ...
"The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases". Cell. 75 (4): 805-816. doi:10.1016/ ... "p21 is a universal inhibitor of cyclin kinases". Nature. 366 (6456): 701-704. Bibcode:1993Natur.366..701X. doi:10.1038/366701a0 ... Yue Xiong and David Beach as a cyclin-CDK-PCNA interacting protein (p21), and as a senescence derived inhibitor by Noda. ... p21(WAF1) was the first mammalian cell cycle inhibitor to be discovered, and was found independently by Wade Harper and Steve ...
1993). "The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases". Cell. 75 (4): 805-16. doi: ... It was identified as a cyclin-dependent kinase inhibitor, and has been shown to interact with, and dephosphorylate CDK2 kinase ... "The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases". Cell. 75 (4): 805-16. doi:10.1016/ ... Cyclin-dependent kinase inhibitor 3 is an enzyme that in humans is encoded by the CDKN3 gene. The protein encoded by this gene ...
... cyclin-dependent kinase inhibitor". Cell Division. 11 (1): 6. doi:10.1186/s13008-016-0019-0. PMC 4840944. PMID 27110270. Li J, ... "The T-box transcription factor TBX3 drives proliferation by direct repression of the p21(WAF1) ... The kinases involved are cyclin A-CDK2 at either SP190 or SP354, p38 mitogen-activated protein (MAP) kinase at SP692 in ... The function of TBX3 is also regulated by phosphorylation by the p38-MAPK, AKT3 and cyclin A/CDK2 and by protein co-factors, ...
The cyclin-dependent cell cycle checkpoint kinase inhibitor-1 CDKN1A (also known as p21) gene harbours promoter G-quadruplex. ... Upon insertion of 8-oxo-dG into thymidine kinase gene of humans, it was determine that if 8-oxo-dG was left unchecked and not ... The RET oncogene functions in the transcription of kinase which has been abundant in certain types of cancer. The guanine rich ... Interaction of this G-quadruplex with TRF2 (also known as TERF2) resulted in epigenetic regulation of p21, which was tested ...
This includes the cyclin-dependent kinase inhibitor P21 and the tumor suppressor gene Pten to promote neural stem cell ... HDAC inhibitors exhibited positive effects on mice with cognitive defects such as Alzheimer's disease and improved the ... DNA demethylation, as well as methylation, of certain genes allows for neurogenesis to proceed in a time dependent manner. One ... It entails many different complex processes which are all time and order dependent. Processes such as neuron proliferation, ...
... and the cyclin dependent kinase inhibitors P27 and P21". Leuk. Lymphoma. 43 (1): 51-7. doi:10.1080/10428190210195. PMID ... Interleukin 1- and interleukin 2-dependent proliferation of activated T cells, and the activation of quiescent helper T cells ... "Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis". Proc. ... "Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation". J. ...
This gene targets the cyclin-dependent kinase inhibitor, p21, and causes cell differentiation, cell cycle arrest in G1, and ... The problem with K562 cells, and many other cancer cell types, is an overabundance of Aurora kinases. These kinases play a role ... However, the overabundance of Aurora kinases allows for uncontrolled cellular division, resulting in cancer. Inhibiting these ...
Increased levels of myostatin up-regulate a cyclin-dependent kinase inhibitor called p21 and thereby inhibit the ... and p21 mRNA levels. This is consistent with the fact that cyclin D1 and p21 upregulation correlates to division and ... Relaix F, Rocancourt D, Mansouri A, Buckingham M (June 2005). "A Pax3/Pax7-dependent population of skeletal muscle progenitor ... Notably, HGF, a cytokine, is transferred from the extracellular matrix into muscles through the nitric-oxide dependent pathway ...
"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... Marzluff WF, Gongidi P, Woods KR, Jin J, Maltais LJ (Oct 2002). "The human and mouse replication-dependent histone genes". ... 1999). "Cloning and characterization of RLPK, a novel RSK-related protein kinase". J. Biol. Chem. 274 (2): 1026-32. doi:10.1074 ... the CDK-activating kinase". J. Biol. Chem. 270 (31): 18195-7. doi:10.1074/jbc.270.31.18195. PMID 7629134. Albig W, Drabent B, ...
The p53 protein binds to DNA, then stimulates the production of a p21, which is also known as cyclin-dependent kinase inhibitor ... However, the p21 cells can trigger apoptosis. Apoptosis or programmed cell death is associated with gradual degradation of the ... Moorad, Jacob A.; Promislow, Daniel E. L. (2008-07-27). "A Theory of Age-Dependent Mutation and Senescence". Genetics. 179 (4 ...
Lastly, studies have also indicated that the mTOR pathway also alters immune responses and stimulates cyclin-dependent kinase ( ... CDK) inhibitors such as p16 and p21. This leads to alteration of the stem-cell niche and results in stem cell exhaustion, ... Mechanistically, the NAD-dependent deacetylase Sirtuin 1 (SIRT-1) is upregulated during low-nutrient periods. SIRT-1 increases ... This cascade results in kinases phosphorylating forkhead transcription factor (FOXO), deactivating it. Deactivation of FOXO ...
Inhibition in MC/CAR Myeloma Cells via Cell Cycle Arrest in Association with Induction of Cyclin-dependent Kinase Inhibitor, ... p21, and Apoptosis". Cancer Research. 60 (3065): 3065-71. PMID 10850458. Retrieved 2010-12-15. "Arsenic in Drinking Water - ... The inositol-requiring enzyme-1 (IRE1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) are two receptors that ... Sykora, P; Snow, E.T (2008). "Modulation of DNA polymerase beta-dependent base excision repair in cultured human cells after ...
"Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ... CDKN2C has been shown to interact with Cyclin-dependent kinase 4 and Cyclin-dependent kinase 6. GRCh38: Ensembl release 89: ... Cyclin-dependent kinase 4 inhibitor C is an enzyme that in humans is encoded by the CDKN2C gene. The protein encoded by this ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". Ewing RM, Chu P, Elisma F, Li H, Taylor P, ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... "Entrez Gene: CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)". Tu Q, Hao J, Zhou X, Yan L, Dai H, Sun B, et al ... Cyclin-dependent kinase 4 inhibitor B also known as multiple tumor suppressor 2 (MTS-2) or p15INK4b is a protein that is ... This gene encodes a cyclin-dependent kinase inhibitor, also known as p15Ink4b protein, which forms a complex with CDK4 or CDK6 ...
CDKN1A, CAP20, CDKN1, CIP1, MDA-6, P21, SDI1, WAF1, p21CIP1, cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase ... cyclin binding. • cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine ... The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.. Cell 75: 805 - 816. PubMed DOI: ... cyclin-dependent protein kinase holoenzyme complex. • PCNA-p21 complex. • perinuclear region of cytoplasm. • клітинне ядро. • ...
2004). "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27( ... Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene. The protein encoded by this ... "Entrez Gene: CDKN2D cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4)". Hirai H, Roussel MF, Kato JY, et al. (1995). " ... 1998). "Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d". ...
"Distinct roles for cyclin-dependent kinases in cell cycle control." Science 262.5142 (1993): 2050-2054. Harlow, E. D., et al. " ... LaBaer, J (1997). "New functional activities for the p21 family of CDK inhibitors". Genes Dev. 11: 847-62. doi:10.1101/gad.11.7 ... "p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5." (1994): 419-423. Meyerson, Matthew, et al. "A family ... Tsai, L (1994). "p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5". Nature. 371: 419-23. doi:10.1038/ ...
... specifically through transcriptional inhibition of cyclin-dependent kinase inhibitors such as p21. CRISPR-Cas9 knockout of the ... Inamoto S, Segil N, Pan ZQ, Kimura M, Roeder RG (November 1997). "The cyclin-dependent kinase-activating kinase (CAK) assembly ... Gonzalez MI, Robins DM (March 2001). "Oct-1 preferentially interacts with androgen receptor in a DNA-dependent manner that ... Schoorlemmer J, Kruijer W (December 1991). "Octamer-dependent regulation of the kFGF gene in embryonal carcinoma and embryonic ...
... primarily through regulation of cyclin D1 and cyclin-dependent kinase inhibitors (p21 and p27) expression. These regulation ... Leung T, Chen XQ, Manser E, Lim L (October 1996). "The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is ... RhoA activates ROCK (RhoA kinase) which stimulates LIM kinase, which then inhibits cofilin, which effectively reorganizes the ... Due to pathophysiological overlap of RhoA and Rho-kinase in asthma, both RhoA and Rho-kinase have become promising new target ...
... and the cyclin dependent kinase inhibitors P27 and P21". Leuk. Lymphoma. 43 (1): 51-7. doi:10.1080/10428190210195. PMID ... CDKN1B has been shown to interact with: AKT1, CKS1B, Cyclin D3, Cyclin E1, Cyclin-dependent kinase 2, Cyclin-dependent kinase 4 ... Cyclin-dependent kinase inhibitor 1B (p27Kip1) is an enzyme inhibitor that in humans is encoded by the CDKN1B gene. It encodes ... vitamin D receptor and cyclin-dependent kinase inhibitors, p21 and p27". Nephrol. Dial. Transplant. 18 Suppl 3 (90003): iii9-12 ...
... and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21". J. Biol. Chem. ... and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21". J. Biol. Chem. ... Henneke G, Koundrioukoff S, Hübscher U (Jul 2003). "Phosphorylation of human Fen1 by cyclin-dependent kinase modulates its role ... FEN1 is an essential enzyme in an inaccurate pathway for repair of double-strand breaks in DNA called microhomology-dependent ...
... and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21". J. Biol. Chem. ... Cyclin D1, Cyclin O, Cyclin-dependent kinase 4, Cyclin-dependent kinase inhibitor 1C, DNMT1, EP300, Establishment of Sister ... "A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor ... "Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... CDK4, CMM3, PSK-J3, cyclin-dependent kinase 4, cyclin dependent kinase 4. ... See also CDK inhibitor for inhibitors of various CDKs. Interactions[edit]. Cyclin-dependent kinase 4 has been shown to interact ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ...
... as well as p21 (cyclin-dependent kinase inhibitor 1), which is involved in pausing cell development for DNA repair. HNRNPK ... May 1999). "Regulated interaction of protein kinase Cdelta with the heterogeneous nuclear ribonucleoprotein K protein". The ... "The multifunctional herpes simplex virus IE63 protein interacts with heterogeneous ribonucleoprotein K and with casein kinase 2 ...
... and degradation of replication licensing factor Cdt1 and cyclin-dependent kinase inhibitor p21 in a proteasome-dependent manner ... Nishitani H, Shiomi Y, Iida H, Michishita M, Takami T, Tsurimoto T (Oct 2008). "CDK inhibitor p21 is degraded by a ... Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A (Sep 2008). "PCNA-dependent regulation of p21 ubiquitylation and ... "Involvement of CUL4 ubiquitin E3 ligases in regulating CDK inhibitors Dacapo/p27Kip1 and cyclin E degradation". Cell Cycle. 5 ( ...
... regulating protein expression levels of the replication licensing factor protein Cdt1 and cyclin-dependent kinase inhibitor p21 ... loss of Cdt2 expression also result in p21 dependent delayed S-phase entry, and re-expression of p21 in S-phase, which results ... Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A (Sep 2008). "PCNA-dependent regulation of p21 ubiquitylation and ... Nishitani H, Shiomi Y, Iida H, Michishita M, Takami T, Tsurimoto T (Oct 2008). "CDK inhibitor p21 is degraded by a ...
GADD45 also works with the cyclin-dependent kinase inhibitor p21, which can cause growth arrest as well. GADD45G is found to be ... GADD45G prevents the kinase ability of the cyclin b1/Cdk1 complex in a fashion that does not break apart the complex. It plays ... Vairapandi M, Balliet AG, Hoffman B, Liebermann DA (2002). "GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role ... It also interacts with CRIF, which causes the inhibition of Cdc2-cyclin B1 and Cdk-cyclin E. ...
CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1).. *↑ a b Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ. The p21 ... 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 ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... Inhibitors[edit]. Another class of regulatory proteins, the Guanosine nucleotide dissociation inhibitors (GDIs), bind to the ... p21-activated kinases *PAK1. *PAK2. *PAK3. *PAK4. *Rho-associated protein kinase *ROCK1 ...
CDKN1A, CAP20, CDKN1, CIP1, MDA-6, P21, SDI1, WAF1, p21CIP1, cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase ... p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin- ... cyclin binding. • cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine ... p21 is a potent cyclin-dependent kinase inhibitor (CKI). The p21 (CIP1/WAF1) protein binds to and inhibits the activity of ...
All these phases in the cell cycle are highly regulated by cyclins, cyclin-dependent kinases, and other cell cycle proteins. ... CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... Generation of pressure is dependent on formin-mediated F-actin nucleation[71] and Rho kinase (ROCK)-mediated myosin II ... This can occur when cells become overcrowded (density-dependent inhibition) or when they differentiate to carry out specific ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... 1omw: Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and ... Buhl AM, Osawa S, Johnson GL (1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human ... 2bcj: Crystal Structure of G Protein-Coupled Receptor Kinase 2 in Complex with Galpha-q and Gbetagamma Subunits ...
CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bad (a Bcl-2 ... Caspases are proteins that are highly conserved, cysteine-dependent aspartate-specific proteases. There are two types of ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... Using these inhibitors it was discovered that cells can die ...
GTP-dependent protein binding. • GTPase activity. • mitogen-activated protein kinase kinase kinase binding. • protein binding. ... CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... "The MAP kinase kinase kinase MLK2 co-localizes with activated ... Activated Cdc42 activates by conformational changes[4] p21-activated kinases PAK1 and PAK2, which in turn initiate actin ...
... and the cyclin dependent kinase inhibitors P27 and P21.». Leuk. Lymphoma 43 (1): 51-7. PMID 11908736. doi:10.1080/ ... de 2000). «Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of ... Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation». J ...
... cyclins and cyclin dependent kinases". Oncogene. 15 (2): 143-57. doi:10.1038/sj.onc.1201252. PMID 9244350.. ... DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator. • positive ... "miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors". Mol. Cell. 41 (2): 210-20. ... "BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site". Mol. Cell. Biol. 19 (7): ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... Gαs activates the cAMP-dependent pathway by stimulating the production of cyclic AMP (cAMP) from ATP. This is accomplished by ... The cAMP-dependent pathway is used as a signal transduction pathway for many hormones including:. *ADH - Promotes water ... cAMP can then act as a second messenger that goes on to interact with and activate protein kinase A (PKA). PKA can ...
... embryogenesis and showed a drastic reduction in the production but increased expression of Cyclin-Dependent Kinase Inhibitors ( ... CDKIs) p21 and p27. Not even upregulation of the other Class I HDACs could compensate for the loss of HDAC1. This inability to ... Binding of HDACs to MEF2 inhibits muscle differentiation, which can be reversed by action of Ca2+/calmodulin-dependent kinase ( ... HDAC inhibitor trichostatin A was reported to reduce stress induced cardiomyocyte autophagy.[54] Studies on p300 and CREB- ...
CDK抑制因子(英语:Cyclin-dependent kinase inhibitor protein). *INK4a/ARF(p14arf/p16、p15、p18、p19) ... Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle. BioEssays. June 1995, 17 (6): 471-80. PMID ... 細胞週期的進行是由不同的週期素(Cyclin)所調控。週期素意味著這些蛋白質的表現量會隨著細胞週期的進行而有所變化,進而確認週期素原來是扮演細胞
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... Indirect/downstream NO modulators: ACE inhibitors/AT-II receptor antagonists (e.g., captopril, losartan) ... p21-activated kinases *PAK1. *PAK2. *PAK3. *PAK4. *Rho-associated protein kinase *ROCK1 ...
... leading to an accumulation of cyclin-dependent kinase inhibitors p21 and p27, and to subsequent G1-phase arrest, as seen in ... Lovastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), an enzyme that catalyzes the ... The first breakthrough in efforts to find a potent, specific, competitive inhibitor of HMG CoA reductase occurred in 1976, when ... Endo, Akira; Kuroda M.; Tsujita Y. (December 1976). "ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis ...
... cyclin-dependent kinase and DREAM complex. When it is time for a cell to enter S phase, complexes of cyclin-dependent kinases ( ... Furthermore, triple knockout, p16 addition, and Cdk 4/6 inhibitor addition experiments confirmed that Cyclin D- Cdk 4/6 is the ... "Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein" ... cyclin E and cyclin A), which push the cell through the cell cycle by activating cyclin-dependent kinases, and a molecule ...
... is inhibited by cyclin dependent kinases (CDKs). CDKs are in turn inhibited by p21. Thus MyoD enhances its own activity in ... In one model of Setdb1 action on MyoD, Setdb1 represses an inhibitor of MyoD. This unidentified inhibitor likely acts ... Both MyoD and pRb are necessary for the repression of cyclin D1, but rather than acting directly on cyclin D1, they act on Fra- ... Cyclin-dependent kinase 4,[30][31]. *Cyclin-dependent kinase inhibitor 1C,[32] ...
"Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ... CDKN2C, INK4C, p18, p18-INK4C, cyclin-dependent kinase inhibitor 2C, cyclin dependent kinase inhibitor 2C. ... CDKN2C‏ (Cyclin dependent kinase inhibitor 2C) هوَ بروتين يُشَفر بواسطة جين CDKN2C في الإنسان.[1][2][3] ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". مؤرشف من الأصل في 05 ديسمبر 2010.. الوسيط , ...
CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... CDK-activating kinase. ... "Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... In humans, cAMP works by activating protein kinase A (PKA, cAMP-dependent protein kinase), one of the first few kinases ... an enzyme called protein kinase A (PKA).[12]. The PKA enzyme is also known as cAMP-dependent enzyme because it gets activated ... Main article: function of cAMP-dependent protein kinase. ... Lim kinase *LIMK1. *LIMK2. *p21-activated kinases *PAK1. *PAK2 ...
CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... April 2010). "Apoptosis induced by Oropouche virus infection in HeLa cells is dependent on virus protein expression". Virus Res ... Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bas (a Bcl-2 ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... Using these inhibitors it was discovered that cells can die ...
... *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... cyclin E, A (Cdk2,1) cyclin A, B, B3 (Cdk1) H. sapiens cyclin D 1,2,3 (Cdk4, Cdk6) cyclin E (Cdk2) cyclin A (Cdk2, Cdk1) cyclin ... Cyclin A / CDK2 - active in S phase.. *Cyclin D / CDK4, Cyclin D / CDK6, and Cyclin E / CDK2 - regulates transition from G1 to ...
The cyclin-dependent kinase inhibitor SCH 727965 (dinacliclib) induces the apoptosis of osteosarcoma cells. „Mol Cancer Ther". ... 6p12-p21. W 16-75% przypadków kostniakomięsaka stwierdza się amplifikację regionu 6p12-p21[75]. W regionie 6p12-p21 jest ... W regionie 6p12-p21 zlokalizowane są również inne istotne geny dla procesu nowotworzenia: protoonkogen PIM1[118], gen VEGF-A ... Glycogen synthase kinase-3β, NF-κB signaling, and tumorigenesis of human osteosarcoma. „J Natl Cancer Inst". 104 (10), s. 749- ...
"Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1". FEBS Letters. 474 (2-3): ... "Sustained activation of the JNK cascade and rapamycin-induced apoptosis are suppressed by p53/p21(Cip1)". Molecular Cell. 11 (6 ... Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 (MAPKK 6) or MAPK/ERK kinase 6 is ... protein kinase binding. • protein serine/threonine kinase activity. • identical protein binding. • MAP kinase kinase activity. ...
de 1993). «The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases». Cell (UNITED STATES) 75 ... de 2002). «Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4». Mol. Cell ... cyclins and cyclin dependent kinases». Oncogene (ENGLAND) 15 (2): 143-57. ISSN 0950-9232. PMID 9244350. doi:10.1038/sj.onc. ... a b «Entrez Gene: CDK2 cyclin-dependent kinase 2». *↑ Berthet C, Aleem E, Coppola V, Tessarollo L, Kaldis P (octubre de 2003). ...
... molecular weight protein inhibitor of cyclin-dependent protein kinases (CDKs) - which has been localised to the p21 region of ... CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) Archived 2004-11-17 at the Wayback Machine from ... Another mutation in the same gene results in a nonfunctional inhibitor of CDK4, a cyclin-dependent kinase that promotes cell ... BRAF inhibitors, such as vemurafenib and dabrafenib and a MEK inhibitor trametinib are the most effective, approved treatments ...
Expression of Myc is highly dependent on BRD4 function in some cancers.[22][23] BET inhibitors have been used to successfully ... The first to be discovered was its capability to drive cell proliferation (upregulates cyclins, downregulates p21), but it also ... "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proceedings of the National ... Gupta S, Davis RJ (October 1994). "MAP kinase binds to the NH2-terminal activation domain of c-Myc". FEBS Letters. 353 (3): 281 ...
MAPKs belong to the CMGC (CDK/MAPK/GSK3/CLK) kinase group. The closest relatives of MAPKs are the cyclin-dependent kinases ( ... Although no MKK1/2 or ERK1/2 inhibitors were developed for clinical use, kinase inhibitors that also inhibit Raf kinases (e.g. ... "Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated ... MAP kinase kinase kinase (MAP3K or MKKK). *MAP kinase kinase kinases *MAP3K1 ...
The MLL fusion gene, MLL-AF4, regulates cyclin-dependent kinase inhibitor CDKN1B (p27kip1) expression. „Proc Natl Acad Sci U S ... p21;q23), t(5;12)(q33;p12), t(5;7)(q33;q11.2), t(5;17)(q33;p13), t(5;10)(q33;q21), t(3;5)(q25;q34). ... Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases.. „Cancer Cell". 19 (1 ... Incorporating FLT3 inhibitors into acute myeloid leukemia treatment regimens. „Leuk Lymphoma". 49 (5), s. 852-63, May 2008. DOI ...
... p21 (WAF1, Cip1), p27Kip1, p16, and p15INK4B, that physically associate with cyclins, cyclin-dependent kinases, or cyclin-Cdk ... Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism. M B ... Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism ... Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism ...
The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.. Harper JW1, Adami GR, Wei N, ... The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has been implicated in the control of the G1 to S ... tight-binding inhibitor of Cdks and can inhibit the phosphorylation of Rb by cyclin A-Cdk2, cyclin E-Cdk2, cyclin D1-Cdk4, and ... Cyclin-Dependent Kinase 2. *Cyclin-Dependent Kinase Inhibitor p21. *Cyclin-Dependent Kinases* ...
Cyclin-Dependent Kinase Inhibitor Proteins [D12.776.624.776.355]. *Cyclin-Dependent Kinase Inhibitor p21 [D12.776.624.776. ... Cyclin-Dependent Kinase Inhibitor p21*Cyclin-Dependent Kinase Inhibitor p21. *Cyclin Dependent Kinase Inhibitor p21 ... "Cyclin-Dependent Kinase Inhibitor p21" by people in Harvard Catalyst Profiles by year, and whether "Cyclin-Dependent Kinase ... A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with ...
The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has been implicated in the control of the G1 to S ... The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases Cell. 1993 Nov 19;75(4):805-16. doi: ... The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has been implicated in the control of the G1 to S ... tight-binding inhibitor of Cdks and can inhibit the phosphorylation of Rb by cyclin A-Cdk2, cyclin E-Cdk2, cyclin D1-Cdk4, and ...
Cyclin kinase inhibitor p21 potentiates bile acid-induced apoptosis in hepatocytes that is dependent on p53. Qiao, L., ... Normal remodeling of the oxygen-injured lung requires the cyclin-dependent kinase inhibitor p21(Cip1/WAF1/Sdi1). Staversky, R.J ... Targeted in vivo expression of the cyclin-dependent kinase inhibitor p21 halts hepatocyte cell-cycle progression, postnatal ... The lack of cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21) in mice increases renal proximal tubular cell death and ...
Cooperative repression of cyclin-dependent kinase inhibitor p21 gene expression by hepatitis B virus X protein and hepatitis C ... and HCV core protein additively repress the universal cyclin-dependent kinase inhibitor p21 gene at the transcription level. ... The transforming growth factor-beta responsive element and Sp1 site of the p21 promoter were responsible for the effect of HCV ... Furthermore, cell growth was additively stimulated by them, suggesting that additive repression of the p21 might be important ...
The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells.. W Poluha, D ... The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells. ... The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells. ... The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells. ...
1994) The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 369:574-578. ... Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in ... Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in ... Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in ...
Expression of cyclin B1 and cyclin dependent kinase inhibitor p21 in lymphocytes in patients with systemic lupus erythematosus. ... Expression of cyclin B1 and cyclin dependent kinase inhibitor p21 in lymphocytes in patients with systemic lupus erythematosus. ... Expression of cyclin B1 and cyclin dependent kinase inhibitor p21 in lymphocytes in patients with systemic lupus erythematosus. ... Expression of cyclin B1 and cyclin dependent kinase inhibitor p21 in lymphocytes in patients with systemic lupus erythematosus. ...
... cyclin-dependent kinase (Cdk), and many others. Expression of the p21 gene is mainly regulated at the transcriptional level. By ... Transfection of recombinant constructs bearing mutations in the p21 NFI site demonstrated that NFI acts as a repressor of p21 ... thereby establishing a role for NFI in the cell cycle dependent expression of p21. ... Inhibition of NFI in human skin fibroblasts through RNAi considerably increased p21 promoter activity suggesting that NFI is a ...
The p21 protein is a negative regulator of mammalian cell cycle progression that functions both by inhibiting cyclin dependent ... This p21-associated cell cycle arrest is associated both with significant inhibition of the phosphorylation of the ... In addition, we demonstrate that localized arterial infection with a p21-encoding adenovirus at the time of balloon angioplasty ... Taken together, these studies demonstrate the important role of p21 in regulating Rb phosphorylation and cell cycle progression ...
Results: The treatment resulted in inhibition of cell proliferation in a dose-and time-dependent manner. p53, p21WAF1and ... "Inhibitory Effect of Ginseng on Breast Cancer Cell Line Growth Via Up-Regulation of Cyclin Dependent Kinase Inhibitor, p21 and ... Inhibitory Effect of Ginseng on Breast Cancer Cell Line Growth Via Up-Regulation of Cyclin Dependent Kinase Inhibitor, p21 and ... Inhibitory Effect of Ginseng on Breast Cancer Cell Line Growth Via Up-Regulation of Cyclin Dependent Kinase Inhibitor, p21 and ...
Cyclin-Dependent Kinase 4 * Cyclin-Dependent Kinase Inhibitor p21 * Cyclin-Dependent Kinases* ... p21 is a universal inhibitor of cyclin kinases Nature. 1993 Dec 16;366(6456):701-4. doi: 10.1038/366701a0. ... Our results indicate that p21 may be a universal inhibitor of cyclin kinases. ... We find that p21 inhibits the activity of each member of the cyclin/CDK family. Furthermore, overexpression of p21 inhibits the ...
... a cyclin dependent kinase (CDK), and a cyclin dependent kinase inhibitor (CDKI). The progression of cells through the cell ... cyclin-dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene. 1995, 11: 211 ... The expression of cyclin-dependent kinase inhibitors p15, p16, p21, and p27 during ovarian follicle growth initiation in the ... Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. Two major classes of CDK ...
The p21 protein, a cyclin-dependent kinase (CDK) inhibitor, is capable of binding to both cyclin-CDK and the proliferating cell ... Dependent Kinase Inhibitor p21 Cyclins metabolism DNA Primers DNA Replication DNA-Binding Proteins metabolism Enzyme Inhibitors ... Waga, S., Stillman, B. (July 1998) Cyclin-dependent kinase inhibitor p21 modulates the DNA primer-template recognition complex. ... Cyclin-dependent kinase inhibitor p21 modulates the DNA primer-template recognition complex ...
p21. Cyclin-dependent kinase inhibitor 1A. PBS. Phosphate-buffered saline. qRT-PCR. Quantitative real-time polymerase chain ... p21 inhibits cyclin D/cyclin-dependent kinase 4 (CDK4) and cyclin E/cyclin-dependent kinase 2 (CDK2), thereby inhibiting cell ... These results suggest that p21 inhibits the function of cyclin-dependent kinase (CDK), arrests the cell cycle, and inhibits ... Moreover, the expression of p21 and MMP1 genes were reduced by embelin in H2O2-treated HDFs in a dose-dependent manner. However ...
... channels and membrane depolarization also caused accumulation of the cyclin-dependent kinase inhibitors p27Kip1 and p21CIP1 in ... Channels and Membrane Depolarization Regulate Accumulation of the Cyclin-Dependent Kinase Inhibitors p27Kip1 and p21CIP1 in ... Channels and Membrane Depolarization Regulate Accumulation of the Cyclin-Dependent Kinase Inhibitors p27Kip1 and p21CIP1 in ... Channels and Membrane Depolarization Regulate Accumulation of the Cyclin-Dependent Kinase Inhibitors p27Kip1 and p21CIP1 in ...
Tissue Microarray Analysis of Cyclin-Dependent Kinase Inhibitors p21 and p16 in Fuchs Dystrophy. Matthaei, Mario; Lackner, Eva- ... Vascular Endothelial Growth Factor Inhibitors for Treatment of Corneal Neovascularization: A Meta-Analysis. Papathanassiou, ...
Cyclin-dependent kinase inhibitor 1A (p21, Cip1). Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human ... cyclin-dependent protein serine/threonine kinase inhibitor activity. • protein binding. • cyclin-dependent protein kinase ... PCNA-p21 complex. Biological process. • regulation of cyclin-dependent protein serine/threonine kinase activity. • G1/S ... cyclin-dependent protein kinase holoenzyme complex. • nucleus. • nucleoplasm. • cytosol. • intracellular membrane-bounded ...
CDKN1A, CAP20, CDKN1, CIP1, MDA-6, P21, SDI1, WAF1, p21CIP1, cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase ... p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin- ... cyclin binding. • cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine ... p21 is a potent cyclin-dependent kinase inhibitor (CKI). The p21 (CIP1/WAF1) protein binds to and inhibits the activity of ...
PI3K Delta InhibitorsThis drug class inhibits one or more of the phosphoinositide 3-kinase enzymes, which are part of the PI3K/ ... p21, inhibitor of cyclin-dependent kinases. ... Pan class I phosphatidylinositol-3-kinase (PI3K) inhibitor with ... Antineoplastics, PI3K Delta Inhibitors. This drug class inhibits one or more of the phosphoinositide 3-kinase enzymes, which ... PI3K, phosphatidylinositide-3 kinase; AKT, protein kinase B; PTEN, phosphatase and tensin homolog; PIP2, phosphatidylinositol-4 ...
... p21, inhibitor of cyclin-dependent kinases. ... PIP3 is generated as a result of BCR-dependent PI3K activation ... PI3K, phosphatidylinositide-3 kinase; AKT, protein kinase B; PTEN, phosphatase and tensin homolog; PIP2, phosphatidylinositol-4 ... B-cell receptor signaling activates PI3K-mediated activation of the kinase AKT, which activates many downstream signaling ... 5-bisphosphate; PIP3, phosphatidylinositol-4,5-trisphosphate; IKK, IkB kinase; mTOR, mammalian target of rapamycin; FoxO, ...
The cyclin-dependent kinase inhibitor p21WAF1 plays a pivotal role in a myriad of processes including cell cycle arrest, ... The T-box transcription factor TBX3 drives proliferation by direct repression of the p21WAF1 cyclin-dependent kinase inhibitor ... Phosphorylation of TBX3 at SP190 can affect its ability to repress p21. a Alignment showing conservation of the S190 residue ( ... b ATDC5 and SW1353 cells were co-transfected with a p21 promoter luciferase reporter construct together with pCMV empty, TBX3 ...
Vitamin D receptor and cyclin-dependent kinase inhibitors, p21 and p27. Together they form a unique fingerprint. * Cyclin- ... T2 - Vitamin D receptor and cyclin-dependent kinase inhibitors, p21 and p27 ... Vitamin D receptor and cyclin-dependent kinase inhibitors, p21 and p27. Nephrology Dialysis Transplantation, 18(SUPPL. 3), iii9 ... Vitamin D receptor and cyclin-dependent kinase inhibitors, p21 and p27, Nephrology Dialysis Transplantation, vol. 18, no. ...
The cyclin-dependent kinase inhibitor p21WAF1/Cip1 is an antiestrogen-regulated inhibitor of Cdk4 in human breast cancer cells ... The cyclin-dependent kinase inhibitor p21,sup,WAF1/Cip1,/sup, is an antiestrogen-regulated inhibitor of Cdk4 in human breast ...
The cyclin-dependent kinase inhibitor p21 (p21WAF1/Cip1) is a multifunctional protein known. * Post author By cellsignaling ... The cyclin-dependent kinase inhibitor p21 (p21WAF1/Cip1) is a multifunctional protein known to promote cell cycle arrest and ... Intro p21cip1/Waf1 (herein after called p21) can be a member from the Cip/Kip family members inhibitors of cell routine ... 1 Fig and C-D. S1A). Therefore p53 can be dispensable for p21 delicate induction of apoptosis by hunger. Knock down of p21 was ...
The p53 homolog p73, contributes to this control by directly upregulating the cyclin dependent kinase inhibitor, p21waf1/cip1. ... Here we provide evidence that p73 upregulates p21 TA in BC tissues and upregulated p21 TA may result from E2F1 upregulation of ... Among BC cell lines with inactivated p53 and wild type p73 (N = 7) there was positive correlation between p73α and p21 TA (p , ... siRNA mediated reduction of p73 TA in the N417 BC cell line was associated with a significant reduction in p21 TA level (p , ...
A functional role of the cyclin-dependent kinase inhibitor 1 (p21(WAF1/CIP1)) for neuronal preconditioningстатья Статья ... A functional role of the cyclin-dependent kinase inhibitor 1 (p21(waf1/cip1)) for neuronal preconditioning / P. Mergenthaler, C ... we show that the HIF-1 target gene cyclin-dependent kinase inhibitor 1, p21(WAF1/CIP1), is essential for neuroprotection by ... that the HIF-1 target gene cyclin-dependent kinase inhibitor 1, p21(WAF1/CIP1), is essential for neuroprotection by hypoxic/ ...
This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin- ... Cyclin-Dependent Kinase 2): CDK2 antibodies CDK2 ELISA Kits CDK2 Proteins CDK2AP2 (Cyclin-Dependent Kinase 2 Associated Protein ... Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which ... MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8): MAP3K8 antibodies MAP3K8 ELISA Kits MAP3K8 Proteins ...
COMP: cartilage oligomeric matrix protein; Sox-9: transcription factor SOX-9; p21: cyclin-dependent kinase inhibitor 1A; p53: ... AMP-activated protein kinase (AMPK), forkhead box O3 (FOXO-3), and sirtuin-1 (SIRT1) genes [30]. In addition to its antioxidant ... In order to evaluate apoptosis in cells, expression of p53 (a), p21 (b), caspase-3 (c), Bcl-2 (d), and BAX (e) was analyzed by ... Using RT-PCR, we showed that ASCEMS treated with AZA/RES displayed diminished expression of the proapoptotic p21 transcript ...
  • The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. (nih.gov)
  • CIP1 encodes a novel 21 kd protein that is found in cyclin A, cyclin D1, cyclin E, and Cdk2 immunoprecipitates. (nih.gov)
  • Berberine enhances posttranslational protein stability of p21/cip1 in breast cancer cells via down-regulation of Akt. (harvard.edu)
  • We show that the Cdk inhibitor p21 Sdi1,Cip1,Waf1 , which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active. (asm.org)
  • The finding that senescent HDF contain elevated amounts of the ubiquitously acting cyclin-dependent kinase inhibitor (CKI) p21 Sdi1,Cip1,Waf1 (p21) ( 40 ) suggested instead that cyclin E-Cdk2 complexes in senescent cells might be inactivated by increased binding of p21. (asm.org)
  • The cyclin-dependent kinase inhibitor 1A (CDKN1A), also known as p21 (WAF1/CIP1) modulates cell cycle, apoptosis, senescence and differentiation via specific protein-protein interactions with the cyclins, cyclin-dependent kinase (Cdk), and many others. (semanticscholar.org)
  • UV radiation is a transcriptional inducer of p21(Cip1/Waf1) cyclin-kinase inhibitor in a p53-independent manner. (semanticscholar.org)
  • Apoptosis, cell proliferation and modulation of cyclin-dependent kinase inhibitor p21(cip1) in vascular remodelling during vein arterialization in the rat. (semanticscholar.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)
  • Our results demonstrate that blockage of K + channels and cell depolarization induce G1 arrest in the OP cell cycle through a mechanism that may involve p27 Kip1 and p21 CIP1 and further support the conclusion that OP cell cycle arrest and differentiation are two uncoupled events. (jneurosci.org)
  • Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA . (wikipedia.org)
  • This article is about the p21 Cip1 protein. (wikipedia.org)
  • p21 Cip1 (alternatively p21 Waf1 ), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1 , is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, [5] though is primarily associated with inhibition of CDK2 . (wikipedia.org)
  • The p21 (CIP1/WAF1) protein binds to and inhibits the activity of cyclin - CDK2 , - CDK1 , and - CDK4 /6 complexes, and thus functions as a regulator of cell cycle progression at G 1 and S phase . (wikipedia.org)
  • The cyclin-dependent kinase inhibitor p21 (p21WAF1/Cip1) is a multifunctional protein known to promote cell cycle arrest and survival in response to p53-dependent and p53 independent stimuli. (cell-signaling-pathways.com)
  • Here, we show that the HIF-1 target gene cyclin-dependent kinase inhibitor 1, p21(WAF1/CIP1), is essential for neuroprotection by hypoxic/aglycemic or erythropoietin preconditioning using wild-type and p21(WAF1/CIP1)-deficient neurons. (ipmnet.ru)
  • Furthermore, overexpression of wild-type p21(WAF1/CIP1) or phospho-mutants significantly increased cell death after hypoxia/aglycemia. (ipmnet.ru)
  • Moreover, deferoxamine-induced endogenous tolerance did not involve p21(WAF1/CIP1) expression in cortical neurons. (ipmnet.ru)
  • Our data suggest that balanced expression and potentially posttranslational regulation of p21(WAF1/CIP1) is required for hypoxic preconditioning. (ipmnet.ru)
  • Here we show that p21 WAF1/CIP1, the prototype inhibitor of cyclin-dependent kinases (CDKs), is required for this coordination in human cells. (biomedsearch.com)
  • Activated STAT proteins specifically recognized the conserved STAT-responsive elements in the promoter of the gene encoding the cyclin-dependent kinase (CDK) inhibitor p21 WAF1/CIP1 and regulated the induction of p21 messenger RNA. (sciencemag.org)
  • The Kip/Cip CKIs, p27 Kip1 and p21 Cip1 , are upregulated during arterial repair and negatively regulate the growth of vascular smooth muscle cells (VSMCs). (ahajournals.org)
  • We hypothesized that a variation in the inactivation of cdk2 and cdk4 during the G 1 phase of the cell cycle by p27 Kip1 , p21 Cip1 , and p16 Ink4 leads to different effects on VSMC growth in vitro and in vivo. (ahajournals.org)
  • Methods and Results -The expression of p27 Kip1 and p21 Cip1 in serum-stimulated VSMCs inactivated cdk2 and cdk4, leading to G 1 growth arrest. (ahajournals.org)
  • Conclusions -p27 Kip1 and p21 Cip1 are potent inhibitors of VSMC growth compared with p16 Ink4 because of their different molecular mechanisms of cyclin-dependent kinase inhibition in the G 1 phase of the cell cycle. (ahajournals.org)
  • The CKIs p27 Kip1 and p21 Cip1 inactivate the cyclin-CDK complexes in the G 1 phase leading to cell cycle arrest, and thus function in growth regulation and wound repair. (ahajournals.org)
  • 6 The molecular mechanisms accounting for the differences in the expression and function of p27 Kip1 , p21 Cip1 , and p16 Ink4 in blood vessels are not known. (ahajournals.org)
  • We hypothesized that differences in the activation of cdk2 and cdk4 by p27 Kip1 , p21 Cip1 , and p16 Ink4 would lead to differential effects on VSMC growth. (ahajournals.org)
  • To test this hypothesis, we examined the effects of p27 Kip1 , p21 Cip1 , and p16 Ink4 on cdk2 and cdk4 activity, G 1 growth arrest, and VSMC proliferation in vitro and in vivo. (ahajournals.org)
  • Recombinant replication-defective adenoviral vectors encoding human p27 Kip1 , p21 Cip1 , p16 Ink4 , and a control vector, AdΔE1, were constructed in an E1A/E3-deleted adenoviral plasmid containing a cytomegalovirus promoter and bovine growth human polyadenylation signal. (ahajournals.org)
  • The cyclin-dependent kinase inhibitor p21 (CIP1, WAF1, CDKN1A ) is thought to be the main executor of p53-induced growth arrest ( 1 - 4 ). (aacrjournals.org)
  • Treatment with lenalidomide significantly inhibited CLL-cell proliferation, an effect that was associated with the p53-independent upregulation of the cyclin-dependent kinase inhibitor p21WAF1/Cip1 (p21). (slideshare.net)
  • Another potent CDK inhibitor, p21 WAF1/CIP1 , is a downstream effector of p53 and controls cell cycle progression by inhibiting the activity of a broader range of CDKs. (nature.com)
  • p27(KIP1) is a member of the CIP1/KIP1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. (thefreedictionary.com)
  • Invitrogen is now offering two new assay kits to measure p27 Kip1 and p21 Waf1/Cip1 protein levels in cell lysates. (thermofisher.com)
  • CDK function is tightly regulated by cell cycle inhibitors such as p21 Waf1/Cip1 and p27 Kip1 proteins. (thermofisher.com)
  • Following anti-mitogenic signals or DNA damage, p21 Waf1/Cip1 and p27 Kip1 bind to cyclin-CDK complexes to inhibit their catalytic activity and induce cell cycle arrest. (thermofisher.com)
  • Figure 2 -Apicidin treatment (2 µg/ml for 24 hours) increases p21 Waf1/Cip1 expression level in MCF-7 cells. (thermofisher.com)
  • Cell extracts were prepared and cell lysates (200 mg/ml) were analyzed with p21 Waf1/Cip1 ELISA Kit (Cat. (thermofisher.com)
  • p21 (WAF1/Cip1) inhibits the activity of each member of the cyclin/Cdk family and over expression of this protein inhibits the proliferation of mammalian cells (5). (genetex.com)
  • Liver mRNA levels of transforming growth factor (TGF)-β1, connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF)-β, cyclin-dependent kinase inhibitor p27 kip (p27), and cyclin-dependent kinase inhibitor p21 WAF1/CIP1 (p21) were quantified by real-time polymerase chain reaction. (aspetjournals.org)
  • DNA-damaging reactive oxygen species (ROS) are a by-product of ionizing radiation that lead to the activation of p53, transcription of p21(cip1/waf1) and, in the case of wild-type TP53 HNSCC cells, cause senescence. (nih.gov)
  • STAT5-induced expression of pim-1 , p21 WAF/Cip1 , and suppressor of cytokine signaling-1/STAT-induced STAT inhibitor-1/Janus kinase binding protein is responsible for induction of proliferation, differentiation, and apoptosis, respectively. (jimmunol.org)
  • Reversible phosphorylation at the C-terminal regulatory domain of p21(Waf1/Cip1) modulates proliferating cell nuclear antigen binding. (wikipedia.org)
  • The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells. (asm.org)
  • identified a protein p21 (WAF1) which was present in cells expressing wild type p53 but not those with mutant p53, moreover constitutive expression of p21 led to cell cycle arrest in a number of cell types. (wikipedia.org)
  • Intro p21cip1/Waf1 (herein after called p21) can be a member from the Cip/Kip family members inhibitors of cell routine progression that affiliates using the BKM120 (NVP-BKM120) cyclin/CDK complexes and with PCNA a processivity element for replication polymerase resulting in the inhibition of CDK actions and DNA replication [1]. (cell-signaling-pathways.com)
  • Białko p21 (WAF1) jest w stanie oddziaływać z jądrowym antygenem komórek proliferujących ( proliferating cell nuclear antigen − PCNA), czynnikiem dodatkowym polimerazy DNA , i tym samym odgrywać rolę regulatora zarówno przy replikacji materiału genetycznego w fazie S jak i przy naprawie łańcucha [5] . (wikipedia.org)
  • Białko p21 (WAF1) należy do CKI bezpośrednio hamujących aktywność kompleksów: cyklina E/CDK2 i cyklina D/CDK4. (wikipedia.org)
  • In addition, CDKN1A mRNA and p21 protein expression were significantly increased in all breast cancer cell lines upon β-catenin silencing. (pubmedcentralcanada.ca)
  • This monoclonal antibody is highly specific to CDKN1A and shows no cross-reaction with other closely related mitotic inhibitors. (abnova.com)
  • The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has been implicated in the control of the G1 to S phase transition in mammals. (nih.gov)
  • p21CIP1 is a potent, tight-binding inhibitor of Cdks and can inhibit the phosphorylation of Rb by cyclin A-Cdk2, cyclin E-Cdk2, cyclin D1-Cdk4, and cyclin D2-Cdk4 complexes. (nih.gov)
  • Phosphorylation of pRb during G 1 phase is carried out by cyclin D-Cdk4 and cyclin D-Cdk6 (cyclin D-Cdk4/6) and cyclin E-Cdk2 complexes ( 44 , 50 , 55 ). (asm.org)
  • In contrast, we have shown previously that although serum-stimulated senescent HDF (IMR90) have abundant cyclin E-Cdk2 complexes, they lack cyclin E-associated kinase activity, a finding consistent with their failure to phosphorylate pRb ( 14 ). (asm.org)
  • Regulation of Cdk2 activity by activating (Thr-160) and inhibiting phosphorylations (Thr-14, Tyr-15) did not account for the lack of cyclin E-Cdk2 kinase activity in senescent cells, i.e., even though approximately one-half of the cyclin E-associated Cdk2 was phosphorylated on Thr-160, treatment with Cdc25 phosphatase to dephosphorylate Thr-14 and Tyr-15 did not increase activity. (asm.org)
  • Cyclin E forms complexes during this interval with CDK2. (biomedcentral.com)
  • Experiments looking at CDK2 activity within single cells have also shown p21 to be responsible for a bifurcation in CDK2 activity following mitosis, cells with high p21 enter a G 0 /quiescent state, whilst those with low p21 continue to proliferate. (wikipedia.org)
  • [15] Follow up work, found evidence that this bistability is underpinned by double negative feedback between p21 and CDK2, where CDK2 inhibits p21 activity via ubiquitin ligase activity. (wikipedia.org)
  • also found that γ-irradiation of fibroblasts induced a p53 and p21 dependent cell cycle arrest, here p21 was found bound to inactive cyclin E / CDK2 complexes. (wikipedia.org)
  • We further show that the CDK inhibitor p21 begins rising in G2 in mother cells whose daughters exit mitosis into the pre-Restriction Point, CDK2 low state. (pnas.org)
  • Furthermore, degradation of p21 coincides with escape from the CDK2 low state and passage through the Restriction Point. (pnas.org)
  • Białko p21 jest silnym inhibitorem kinaz zależnych od cyklin (CKI): wiąże się z kompleksami cyklin CDK2 lub CDK4 , hamując ich aktywność. (wikipedia.org)
  • p16 Ink4 inhibited cdk4, but not cdk2, kinase activity, producing partial inhibition of VSMC growth in vitro. (ahajournals.org)
  • Progression through G 1 and entry into the S phase is regulated by the formation and activation of cyclin/cyclin-dependent kinase (CDK) complexes, predominantly cyclin D-cdk4/6 and cyclin E-cdk2. (ahajournals.org)
  • The occurrence of p21 in the nucleus executes binding and inhibition activity of cyclin dependent kinases Cdk1 and Cdk2, and blocks the transition from G1 phase into S phase or from G2 phase into mitosis after DNA damage, which enables the repair of damaged DNA. (thermofisher.com)
  • Transcriptionally induced by p53, the p21 protein binds and inhibits the cdk2-cyclin B/E complexes but increases stability and nuclear localization of cyclin D, stimulating assembly of the cdk4-cyclin D complex ( 3 , 5 - 13 ). (aacrjournals.org)
  • The p21 protein binds to and inhibits the activity of cyclin-CDK2 and cyclin-CDK1 complexes, and thus functions as a regulator of cell cycle progression at G1 and S phase. (cmelist.com)
  • We also provide new evidence that p21 may play a role in inactivation of the DNA replication factor proliferating cell nuclear antigen during early senescence. (asm.org)
  • In normal cells, CDKs exist predominantly in multiple quaternary complexes, each containing a CDK, cyclin, proliferating cell nuclear antigen and the p21 protein. (nih.gov)
  • However, in many transformed cells, proliferating cell nuclear antigen and p21 are lost from these multiprotein enzymes. (nih.gov)
  • The p21 protein, a cyclin-dependent kinase (CDK) inhibitor, is capable of binding to both cyclin-CDK and the proliferating cell nuclear antigen (PCNA). (cshl.edu)
  • p21 interacts with proliferating cell nuclear antigen ( PCNA ), a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. (wikipedia.org)
  • Furthermore, the senescent-cell-cycle arrest occurs prior to the accumulation of the Cdk4-Cdk6 inhibitor p16 Ink4a , suggesting that p21 may be sufficient for this event. (asm.org)
  • Instead, the cyclin D1-Cdk4 and cyclin D1-Cdk6 complexes in these cells are associated with an increased amount of p21, suggesting that p21 may be responsible for inactivation of both cyclin E- and cyclin D1-associated kinase activity at the early stage of senescence. (asm.org)
  • Moreover, even in the late stage of senescence when p16 is high, cyclin D1-Cdk4 complexes are persistent, albeit reduced by ≤50% compared to young cells. (asm.org)
  • The protein encoded by the p16INK4a inhibits formation of CDK-cyclin-D complexes by competitive binding of CDK4 and CDK6. (genome.jp)
  • 23 24 p16 INK4a exerts a tumor-suppressive function by specifically interfering with the catalytic activity of complexes between cyclin D and cyclin-dependent kinase 4 (CDK4) or CDK6. (nature.com)
  • 25 This inhibitory effect on cyclin D/CDK4(6) complexes prevents phosphorylation of the retinoblastoma protein (Rb) and the subsequent release of transcription factors that are required for passage into and through S phase, in particular members of the E2F transcription factor family. (nature.com)
  • Real-time RT-PCR demonstrated that the expression of the cell cycle-driving molecule, cyclin-dependent kinase 4 (Cdk4), in HCC was significantly reduced by the treatments with vitamin K2, K3 and K5. (thefreedictionary.com)
  • The increased protein expression of p27 results in cellular arrest by binding to cyclin/Cdk complexes, like cyclin D1/Cdk4 (4,8). (genetex.com)
  • The irreversible G 1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G 1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). (asm.org)
  • Cyclins and CDKs assemble into complexes with one another as cells progress through G1 phase, cyclins being required to activate the serine-threonine kinase activity of their catalytic partners. (biomedcentral.com)
  • The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (biomedcentral.com)
  • Here we have investigated the significance of this phenomenon by molecular cloning of p21 and in vitro reconstitution of the quaternary cell-cycle kinase complexes. (nih.gov)
  • We also suggest that the p21-PCNA complex that remains attached to DNA might function to tether cyclin-CDK complexes to specific regions of the genome. (cshl.edu)
  • [12] [13] The binding of p21 to CDK complexes occurs through p21's N-terminal domain, which is homologous to the other CIP/KIP CDK inhibitors p27 and p57 . (wikipedia.org)
  • The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at the G1 pahse. (jax.org)
  • Cyclin-dependent kinase inhibitor 1C is a tight-binding inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. (wikipedia.org)
  • It encodes a cell cycle inhibitor that binds to G1 cyclin-CDK complexes. (wikipedia.org)
  • p53 and p21 may form complexes with many other proteins. (aacrjournals.org)
  • Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (biomedcentral.com)
  • Seven cyclin-dependent kinase inhibitor proteins have thus far been identified. (wikipedia.org)
  • In recent years, many orthologues of the Snail family have been identified throughout the animal kingdom, and their study is providing new clues about the EMT-dependent and -independent functions of Snail proteins. (biologists.org)
  • Silencing cereblon (CRBN), a known molecular target of lenalidomide, impaired the capacity of lenalidomide to induce expression of p21, inhibit CD154-induced CLL-cell proliferation, or enhance the degradation of Ikaros family zinc finger proteins 1 and 3 (IKZF1 and IKZF3). (slideshare.net)
  • Interactions of endogenous proteins p53 and p21 in IMR-32 neuroblastoma and H460 lung cancer cells. (aacrjournals.org)
  • A major finding of our article is that the p53/p21 complex is a functional unit that can act on multiple cellular components and that prosurvival Bcl-2 proteins are targets of the p53/p21 complex. (aacrjournals.org)
  • Histone deacetylase inhibitors (HDACi) are a recently developed class of anticancer agents that cause increased acetylation of core histones and nonhistone proteins leading to modulation of gene expression and protein activity involved in cancer cell growth and survival pathways. (aacrjournals.org)
  • As cyclin-dependent kinase (CDK) inhibitors, both proteins are negative cell cycle regulators that play an important role in tumor suppression. (thermofisher.com)
  • The TARA proteins share evolutionarily conserved motifs with several recently characterized mammalian nuclear proteins, including the cyclin-dependent kinase regulator TRIP-Br1/p34 SEI-1 , the related protein TRIP-Br2/Y127, and RBT1, a partner of replication protein A. These data raise the possibility that TARA-α/-β play a role in integrating chromatin structure with cell cycle regulation. (genetics.org)
  • Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). (biomedcentral.com)
  • CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs). (biomedcentral.com)
  • The progression of cells through the cell cycle is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs). (biomedcentral.com)
  • Cyclins function as the positive regulators of CDKs. (biomedcentral.com)
  • Compared with normal human fibroblasts, cells transformed with a variety of viral oncoproteins show striking changes in the subunit composition of the cyclin-dependent kinases (CDKs). (nih.gov)
  • More than 10 years ago, the discovery of cyclin-dependent ki- nases (Cdks) ushered in a new era in the understanding of cell proliferation and its control. (springer.com)
  • For example, although Cdks appear to be highly conserved phylogenetically, cyclins are much less so. (springer.com)
  • Eukaryotic cell cycle progression is driven by cyclin-dependent kinases (CDKs) and cyclins. (biologists.org)
  • Cell division relies on the activation of cyclins, which bind to CDKs to induce cell cycle progression towards S phase and later to initiate mitosis. (thermofisher.com)
  • Cell cycle progression is regulated by cyclins and their cognate Cdks (1-3). (genetex.com)
  • The treatment resulted in inhibition of cell proliferation in a dose-and time-dependent manner. (waocp.org)
  • Software analysis and PCR array analysis showed an increase in the expression of p21 and p38 MAP kinases after the inhibition of miR-21 and decreased expression of cyclins and cyclin dependent kinases. (pubmedcentralcanada.ca)
  • We found that JunB suppresses p21 induction through inhibition of its promoter activity. (biochemj.org)
  • Inhibition of cyclin D1 expression and phosphorylation of retinoblastoma protein by phosmidosine, a nucleotide antibiotic. (nii.ac.jp)
  • Both glutaminase siRNA and glutaminase inhibition have been shown to be effective in in vitro models of cancer and HAD, suggesting a potential role for small molecule glutaminase inhibitors. (worldwidescience.org)
  • The newly identified inhibitors exhibited 10 to 1500-fold greater affinities than DON and BPTES and over 100-fold increased efficiency of inhibition. (worldwidescience.org)
  • Rapamycin influences the cell cycle by up-regulation of p27, down-regulation of p21, and inhibition of p70 s6k phosphorylation. (aspetjournals.org)
  • The TGF-beta-induced cell cycle arrest has been partially attributed to the regulatory effects of TGF-beta on both the levels and the activities of the G1 cyclins and their kinase partners. (pnas.org)
  • We demonstrate that TGF-beta also causes a rapid transcriptional induction of p21, suggesting that p21 can respond to both intracellular and extracellular signals for cell cycle arrest. (pnas.org)
  • A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. (harvard.edu)
  • Since p21 decreases after senescence is achieved, this upregulation of p16 may be essential for maintenance of the senescent-cell-cycle arrest. (asm.org)
  • are not involved in ion channel-dependent cell cycle arrest in OP cells. (jneurosci.org)
  • [6] [7] p21 represents a major target of p53 activity and thus is associated with linking DNA damage to cell cycle arrest. (wikipedia.org)
  • Studies of p53 dependent cell cycle arrest in response to DNA damage identified p21 as the primary mediator of downstream cell cycle arrest. (wikipedia.org)
  • p21 can be a p53 focus on gene which is another mediator of p53 induced cell BMPR1A routine arrest in response to DNA damaging real estate agents and/or oncogenic tension [1] [2]. (cell-signaling-pathways.com)
  • In the absence of p21, DNA-damaged cells arrest in a G2-like state, but then undergo additional S phases without intervening normal mitoses. (biomedsearch.com)
  • The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. (jax.org)
  • Cells pre-Restriction Point are uncommitted to the cell cycle and can arrest at the Restriction Point, whereas cells post-Restriction Point are no longer dependent on mitogens and will complete one round of division, even in the absence of mitogens. (pnas.org)
  • 2 Cyclin-dependent kinase inhibitors (CKIs) are naturally occurring gene products that inhibit the cyclin-CDK activity leading to G 1 arrest. (ahajournals.org)
  • p21 is a main effector of growth arrest induced by p53. (aacrjournals.org)
  • Interestingly, a second p53-induced transcript from the p21 gene, p21B ( Fig. 1 ) was recently identified and found to encode a protein expressing proapoptotic activity ( 14 ), suggesting a role for the p21 gene in both cell cycle arrest and apoptosis. (aacrjournals.org)
  • In addition to growth arrest, p21 can mediate cellular senescence. (cmelist.com)
  • Western blotting was used to measure cyclin-dependent kinase (CDK) inhibitors p21 and p27 that arrest cell cycle. (thefreedictionary.com)
  • These findings indicate that amifostine-induced G1 arrest and cytoprotection are mediated via a pathway that is dependent on p53 protein and that amifostine-induced expression of p21 protein is not sufficient to sustain a G1 arrest or to mediate cytoprotection. (nih.gov)
  • Cooperative repression of cyclin-dependent kinase inhibitor p21 gene expression by hepatitis B virus X protein and hepatitis C virus core protein. (nih.gov)
  • Here, we demonstrated that HBV X protein (HBx) and HCV core protein additively repress the universal cyclin-dependent kinase inhibitor p21 gene at the transcription level. (nih.gov)
  • Expression of the p21 gene is mainly regulated at the transcriptional level. (semanticscholar.org)
  • The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. (antibodies-online.com)
  • The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. (antibodies-online.com)
  • This gene encodes a potent cyclin-dependent kinase inhibitor. (jax.org)
  • Cyclin-dependent kinase inhibitor 1C (p57, Kip2), also known as CDKN1C, is a protein which in humans is encoded by the CDKN1C imprinted gene. (wikipedia.org)
  • p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors. (uniprot.org)
  • We previously analyzed p21 status in breast cancer and reported two novel polymorphisms of the p21 gene. (aacrjournals.org)
  • We detected five polymorphisms of the p21 gene. (aacrjournals.org)
  • The finding of an association between locally advanced breast cancer and one particular polymorphism of the p21 gene suggests this polymorphism to be related to tumor behavior, including enhanced growth rate. (aacrjournals.org)
  • Point mutations within the K-RAS gene inactivate GTPase activity and the p21-RAS protein continuously transmits growth signals to the nucleus. (genome.jp)
  • Gene expression profiles of ovarian cancer cells treated with ACFP were generated by cDNA microarray, and the expression of apoptotic-specific genes, such as bcl -xl, bax , akt , caspase -3, CDC 25C and cyclin B1, was assessed by real time PCR and western blot analysis. (biomedcentral.com)
  • Gene expression profiling highlighted that ACFP treatment in ovarian cancer cells repressed the expression of bcl- xl, akt , CDC 25C and cyclin B1 and promoted the expression of bax and caspase -3 in a time- and dose-dependent manner. (biomedcentral.com)
  • However p21 may inhibit apoptosis and does not induce cell death on its own. (wikipedia.org)
  • [23] The ability of p21 to inhibit apoptosis in response to replication fork stress has also been reported. (wikipedia.org)
  • Although p21 may become an apoptosis inducer using instances results acquired in many versions indicate it comes with an anti-apoptotic impact when cells are treated by genotoxic real estate agents [7]-[10]. (cell-signaling-pathways.com)
  • Therefore p53 can be dispensable for p21 delicate induction of apoptosis by hunger. (cell-signaling-pathways.com)
  • Serum-nutrient starvation induced an apoptosis response mediated by Puma BKM120 (NVP-BKM120) and Bax in p21? (cell-signaling-pathways.com)
  • we assessed apoptosis amounts in wild-type p21? (cell-signaling-pathways.com)
  • This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of cyclin-dependent kinase2, and may be instrumental in the execution of apoptosis following caspase activation. (jax.org)
  • Rodriguez R, Meuth M. Chk1 and p21 cooperate to prevent apoptosis during DNA replication fork stress . (wikipedia.org)
  • In this study, we compared chemosensitivity, cell cycle distribution, and apoptosis on noscapine treatment in four cell lines derived from the colorectal carcinoma HCT116 cells: p53 +/+ (p53-wt), p53 −/− (p53-null), p21 −/− (p21-null), and BAX −/− (BAX-null). (aacrjournals.org)
  • Interestingly, despite increased levels of p53, p21-null cells were resistant to apoptosis, suggesting a proapoptotic role of p21 and implying that p53 is a necessary but not sufficient condition for noscapine-mediated apoptosis. (aacrjournals.org)
  • P21 exhibits a dual function in carcinogenesis, and acts as a tumor suppressor, prevents apoptosis, and acts as an oncogene. (thermofisher.com)
  • We discussed the possibility that the p53/p21 complex regulates cell functions other than invasion and apoptosis by binding to other targets. (aacrjournals.org)
  • Altered prostatic epithelial proliferation and apoptosis, prostatic development and serum testosterone in mice lacking cyclin-dependent kinase inhibitors," Biology of Reproduction 73(5): 951-958. (thefreedictionary.com)
  • LincRNA-p21 participates in TP53 -dependent transcriptional repression leading to apoptosis and seem to have to effect on cell-cycle regulation. (rcsb.org)
  • Using these constitutively active forms of STAT5, we found that activation of STAT5 induced cytokine-independent growth of IL-3-dependent cells ( 8 , 9 ), and that STAT5 manifested a variety of biological functions including proliferation, differentiation, and apoptosis of Ba/F3 cells through up-regulation of a variety of target genes of STAT5 ( 10 ). (jimmunol.org)
  • Extracellular-Regulated Protein Kinase 5-Mediated Control of p21 Expression Promotes Macrophage Proliferation Associated with Tumor Growth and Metastasis. (harvard.edu)
  • The lncRNA SLNCR Recruits the Androgen Receptor to EGR1-Bound Genes in Melanoma and Inhibits Expression of Tumor Suppressor p21. (harvard.edu)
  • In quiescent young HDF, cyclin D1 and cyclin E are present in low amounts, but upon serum stimulation both their expression and their associated kinase activities increase during the mid and late G 1 phases, respectively ( 14 , 50 ). (asm.org)
  • Expression of cyclin B1 and cyclin dependent kinase inhibitor p21 in lymphocytes in patients with systemic lupus erythematosus. (jrheum.org)
  • We measured the expression of cyclin B1 and CDK inhibitor p21 in peripheral blood lymphocytes (PBL) from patients with SLE and controls. (jrheum.org)
  • Bivariate distribution of cyclin B1 or p21 expression versus cellular DNA content was assessed by flow cytometry. (jrheum.org)
  • Expression of cyclin B1 was similar in all groups. (jrheum.org)
  • Adenovirus-mediated over-expression of the cyclin/cyclin-dependent kinase inhibitor, p21 inhibits vascular smooth muscle cell proliferation and neointima formation in the rat carotid artery model of balloon angioplasty. (semanticscholar.org)
  • In this study we tested the expression of CDKIs p15, p16, p21 and p27 by immunohistochemistry to determine the role of CDKIs in the initiation of primordial follicle growth. (biomedcentral.com)
  • Expression of p15, p16, p21 and p27 did not vary in granulosa and theca cells by the follicle stage. (biomedcentral.com)
  • p15, p16, p21 and p27 in mouse ovaries by immunohistochemistry to assess whether the initiation of primordial follicle growth was associated with the expression of CDKIs. (biomedcentral.com)
  • Moreover, the expression of p21 and MMP1 genes were reduced by embelin in H 2 O 2 -treated HDFs in a dose-dependent manner. (springer.com)
  • b ATDC5 and SW1353 cells were co-transfected with a p21 promoter luciferase reporter construct together with pCMV empty, TBX3 WT, TBX3 S190A or TBX3 S190E expression constructs. (biomedcentral.com)
  • In order to elucidate the mechanism of parathyroid cell proliferation, the expression of CDKIs, p21 and p27, and the VDR was analysed immunohistochemically, and compared among nodular and diffuse hyperplastic parathyroid glands, and histologically normal parathyroid glands. (elsevier.com)
  • The expression of both p21 and p27 was also significantly lower in nodular hyperplasias than in diffuse hyperplasias or normal parathyroid glands. (elsevier.com)
  • Sections of parathyroid glands with a high expression of nuclear VDR highly expressed both p21 and p27. (elsevier.com)
  • In nodular hyperplasias, the expression of both p21 and p27 correlated either positively with the nuclear VDR expression or inversely with the glandular weight. (elsevier.com)
  • Therefore, the reduced expression of p21 and p27, being VDR dependent, is a major pathogenic factor for nodular parathyroid gland growth in advanced 2HPT. (elsevier.com)
  • Of take note p53 expression had not been suffering from knock down of p21 by RNA disturbance in HCT116 wt cells recommending that cell loss of life induced in p21 depleted cells can be unlikely to derive from improved p53 amounts (Fig. 1C). (cell-signaling-pathways.com)
  • cells to hunger can be genuinely because of the insufficient p21 expression which stabilisation of p53 can be unlikely to are likely involved. (cell-signaling-pathways.com)
  • Western blot analysis showed an increase in the expression of p21 and p38 MAP kinase genes and a reduction in cyclin E2. (pubmedcentralcanada.ca)
  • Li Y, Jenkins CW, Nichols MA, Xiong Y. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21 . (wikipedia.org)
  • Bedelbaeva K, Snyder A, Gourevitch D, Clark L, Zhang X-M, Leferovich J, Cheverud JM, Lieberman P, Heber-Katz E. Lack of p21 expression links cell cycle control and appendage regeneration in mice . (wikipedia.org)
  • Conversely, loss of p53 and p21 alleles had a counter effect on both BAX and Bcl-2 expression and the p53-null and p21-null cells were significantly resistant to the antiproliferative and apoptotic effects of noscapine. (aacrjournals.org)
  • Although drug-dependent microtubule disruption results in the up-regulation of p53 expression, the relationship between p53-driven genes and drug sensitivity remains controversial as the response is drug and cell type dependent. (aacrjournals.org)
  • Background -The cyclin-dependent kinase inhibitors (CKIs) have different patterns of expression in vascular diseases. (ahajournals.org)
  • Because c-Abl promotes expression of the cyclin-dependent kinase inhibitor p21 upon stimulation with the DNA-damaging agent Adriamycin (doxorubicin), we analysed the involvement of JunB in Adriamycin-induced p21 expression. (biochemj.org)
  • Therefore JunB is likely to be a key target of c-Abl in expression of p21 in Adriamycin-induced DDR. (biochemj.org)
  • In the following experiments, we found that CDCA2 regulated CCND1 expression through activating the PI3K/AKT pathway, and confirmed this using a specific PI3K inhibitor (LY294002). (springer.com)
  • Alterations in the levels of p53 or p21 expression did not significantly influence cell growth during similar incubation periods ( 3 ). (aacrjournals.org)
  • Furthermore, infected cells abolished their expression of the tumor protein p53 and induced an increase in the expression of cyclin-dependent kinase inhibitors p21 and p27 to 2.6-fold and 4.2-fold of controls, respectively. (biologists.org)
  • Ruiling Zhang and team from Xinxiang Medical University explored the correlation between cyclin-dependent kinase 5 expression in the hippocampus and neurological impairments following prenatal ethanol exposure, and found that prenatal ethanol exposure could affect cyclin-dependent kinase 5 and its activator p35 in the hippocampus of offspring rats. (thefreedictionary.com)
  • The expression of p21 is inducible by a wide range of stress stimuli and its transcription can be enhanced by p53 (6). (genetex.com)
  • Primary antibody (at 1:200) used to detect p21 expression by western blot. (genetex.com)
  • Amifostine induced the expression of p53 protein in p53-proficient cells and the expression of p21 protein in both p53-proficient and -deficient cells. (nih.gov)
  • The expression of p21 and production of ROS have been associated with the induction of cellular senescence, but the intricate relationship between p21 and ROS and how they work together to induce senescence remains elusive. (nih.gov)
  • For the first time, we show that persistent exposure to low levels of the ROS, hydrogen peroxide, leads to the long-term expression of p21 in HNSCC cells with a partially functional TP53, resulting in senescence. (nih.gov)
  • Our data offer a rationale to consider the use of either ROS inducing agents or therapies that increase p21 expression in combination with radiation as approaches in cancer therapy and emphasizes the importance of considering TP53 status when selecting a patient's treatment options. (nih.gov)
  • Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. (wikipedia.org)
  • P21 is able to bind to and inhibit caspase 3, as well as the apoptotic kinases ASK1 and JNK. (thermofisher.com)
  • Silencing p21 with small interfering RNA (siRNA) impaired the capacity of lenalidomide to inhibit CLL-cell proliferation. (slideshare.net)
  • These results indicate that lenalidomide can directly inhibit proliferation of CLL cells in a CRBN/p21-dependent, but p53-independent, manner at concentrations achievable in vivo, potentially contributing to the capacity of this drug to inhibit disease- progression in patients with CLL. (slideshare.net)
  • Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16. (asm.org)
  • Phosphorylation of TBX3 at SP190 can affect its ability to repress p21. (biomedcentral.com)
  • The phosphomimetic JunB, which was generated by glutamic acid substitutions at the phosphorylation sites, failed to repress p21 induction. (biochemj.org)
  • Not only were both of the known cell cycle transitions, from G 1 to S phase and G2 to M phase, found to be dependent on these protein kinases, but the reg- ulatory assumption intrinsic to cyclin-dependent kinases, a stable inactive catalytic subunit (the Cdk) and an unstable requisite positive regulatory activating subunit (the cyclin), led to a simple model for cell cycle control. (springer.com)
  • The cell line studied in these experiments, HaCaT, contains two mutant alleles of p53, which are unable to activate transcription from the p21 promoter when overexpressed. (pnas.org)
  • The crucial role of DNA-dependent protein kinase and myelin transcription factor 1-like protein in the miR-141 tumor suppressor network. (harvard.edu)
  • In the myelomonocytic cell line, active vitamin D 3 is known to activate the transcription of both p21 and p27, cyclin-dependent kinase inhibitors (CDKIs), regulating the transition from the G 1 to the S phase of the cell cycle, in a VDR-dependent manner. (elsevier.com)
  • Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. (rcsb.org)
  • We conclude that the level of ROS is crucial in initiating p53's transcription of p21 leading to senescence. (nih.gov)
  • Our findings suggest that the regulation of c-Myc in breast cancer cells is dependent on the molecular subtype, and that β-catenin-mediated regulation of c-Myc and p21 may control the balance of cell death and proliferation in breast cancer. (pubmedcentralcanada.ca)
  • Taken together, these findings suggest that TGF-beta can induce p21 through a p53-independent pathway. (pnas.org)
  • This drug class inhibits one or more of the phosphoinositide 3-kinase enzymes, which are part of the PI3K/AKT/mTOR pathway, an important signalling pathway for many cellular functions such as growth control, metabolism and translation initiation. (medscape.com)
  • Under these circumstances p21 prevents Puma and its own downstream effector Bax from triggering the mitochondrial apoptotic pathway. (cell-signaling-pathways.com)
  • lacking cells To check if the mitochondrial apoptotic pathway could take into account hunger induced cell loss of life in HCT116 p21? (cell-signaling-pathways.com)
  • The key regulator of the PI3K/Akt pathway is Akt/PKB, a family of three closely related serine/threonine-protein kinases. (antibodies-online.com)
  • The STAT signaling pathway appears to negatively regulate the cell cycle by inducing CDK inhibitors in response to cytokines. (sciencemag.org)
  • We have previously discovered the naturally occurring antitussive alkaloid noscapine as a tubulin-binding agent that attenuates microtubule dynamics and arrests mammalian cells at mitosis via activation of the c-Jun NH 2 -terminal kinase pathway. (aacrjournals.org)
  • Mike Nickerson ( [email protected] ) included negative feedback to IRS1 and 2 from the PI3 kinase pathway. (cancer.gov)
  • Activation of two major intracellular signaling cascades, the phosphoinositide-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and the mitogen-activated Erk kinase (MEK)/extracellular signal-regulated kinase (Erk) pathway, have been found to be involved in the survival and proliferation of SCLC ( 3 , 5 - 8 ). (aacrjournals.org)
  • p21 is a potent cyclin-dependent kinase inhibitor (CKI). (wikipedia.org)
  • Here, we report the identification of potent and selective small-molecule inhibitors of the MDM2-p53 interaction with in vitro and in vivo antitumor activity. (sciencemag.org)
  • However, there are no potent, selective inhibitors of glutaminase currently available. (worldwidescience.org)
  • Through its binding to PCNA, p21 can regulate the function of PCNA differentially in replication and repair. (cshl.edu)
  • It has been hypothesized that voltage-dependent K + channel activity could regulate mitogenesis in the nervous system by maintaining the membrane potential hyperpolarized, a condition necessary for progression through G1 phase restriction points ( Wonderlin and Strobl, 1996 ). (jneurosci.org)
  • and (2) cyclins and cyclin-dependent kinase inhibitors (cdkis) known to regulate cell cycle progression through this phase are affected by ion channel activity or changes in membrane potential. (jneurosci.org)
  • For both cell lines, RP215 and anti-antigen receptors were found to regulate similarly and consistently a number of genes including NFκB-1, IgG, P21, Cyclin D1, ribosomal P1 and c-fos with only exceptions for EGFR and ribosomal P0. (omicsonline.org)
  • We found that p21 knockdown with or without cytoplasmic p53 (p53 K305N ) did not significantly influence cell growth in serum-free and 10% FBS-containing media ( Fig. 2 ), suggesting that p21 can regulate cell invasion without significantly altering cell growth. (aacrjournals.org)
  • Kinases regulate many essential cellular processes. (thefreedictionary.com)
  • Using these isogenic variants, we investigated the roles of p53, BAX, and p21 in the cellular response to treatment with noscapine. (aacrjournals.org)
  • In this scenario, the role played by p21 is particularly intriguing because this protein can be activated by both p53-dependent and p53-independent mechanisms and can assume proapoptotic or antiapoptotic functions, depending on the cellular context ( 14 ). (aacrjournals.org)
  • The binding of the p53/p21 complex to its targets may depend on various factors, including subcellular localization of p53 and p21, cellular physiology, and extracellular stressors. (aacrjournals.org)
  • These results indicate that SSRP1 is a novel cellular protein involved in LANA-dependent DNA replication. (labome.org)
  • Jim DeCaprio ( [email protected] ) suggested adding cyclin D2 (CCND2) and 3 (CCND3) in addition to Cyclin D1 (CCND1) as MAPK targets. (cancer.gov)
  • Which medications in the drug class Antineoplastics, PI3K Delta Inhibitors are used in the treatment of Diffuse Large Cell Lymphoma? (medscape.com)
  • Pan class I phosphatidylinositol-3-kinase (PI3K) inhibitor with predominant inhibitory activity against PI3K-alpha and PI3K-delta isoforms expressed in malignant B cells. (medscape.com)
  • Upon activation by receptor tyrosine kinase PI3K phosphorylates PIP2 to PIP3 which then activates Akt signaling. (antibodies-online.com)
  • p53 overexpression did not induce p21, bax, or mdm2 in neurons. (jneurosci.org)
  • This anti-apoptotic impact can be exerted through the cytosol nonetheless it can be unrelated to the power of p21 to hinder the effector caspase 3. (cell-signaling-pathways.com)
  • Protein analysis of treated tumor biopsies revealed elevated amounts of cell cycle regulators such as p21 and proapoptosis factors, such as caspase 3 and 7 and cleaved poly[ADP-ribose] polymerase, coupled with decreased levels of antiapoptotic factors such as Bcl-2 and Bcl-X L . These studies together suggest that panobinostat may be a useful adjunct in the treatment of thoracic malignancies, especially SCLC. (aacrjournals.org)
  • Interestingly, even though HR was stimulated by the presence of a viral origin of DNA replication, virally stimulated HR could proceed in the presence of the DNA synthesis inhibitor aphidicolin. (labome.org)
  • D-type cyclins are usually synthesized by mid-G1 phase and accumulate to a maximum as cells advance through the G1/S boundary. (biomedcentral.com)
  • Furthermore, overexpression of p21 inhibits the proliferation of mammalian cells. (nih.gov)
  • The antiproliferative effects of K + channel blockers and veratridine were still present in OP cells isolated from INK4a −/− mice, lacking the cyclin-dependent kinase inhibitors p16 INK4a and p19 ARF . (jneurosci.org)
  • [26] Working in mouse models, it was also shown that whilst mice lacking p21 were healthy, spontaneous tumours developed and G1 checkpoint control was compromised in cells derived from these mice. (wikipedia.org)
  • Left panel lysates from SW1353 cells transfected with empty vector, TBX3WT, TBX3 S190A or TBX3 S190E constructs were incubated with a biotinylated probe matching the T-element at position -121 bp of the p21 promoter. (biomedcentral.com)
  • Therefore an insufficient source in nutrients might not come with an overt influence on tumor cell viability because of p21 induction nonetheless it primes these cells to perish and sensitizes these to the deleterious ramifications of Bcl-xL inhibitors no matter their p53 position. (cell-signaling-pathways.com)
  • Therefore that p21 might are likely involved in the success of tumor cells that will go beyond circumstances of BKM120 (NVP-BKM120) the p53 reliant response to severe genotoxic stress. (cell-signaling-pathways.com)
  • cells to hunger induced cell loss of life was a primary outcome of p21 lack. (cell-signaling-pathways.com)
  • Silencing of p21 was adequate to sensitize HCTT116 wt cells to hunger induced cell loss of life (Fig. 1C). (cell-signaling-pathways.com)
  • On the other hand silencing of p53 got no influence on the viability of starved HCT116 wt cells and didn't protect HCT116 p21? (cell-signaling-pathways.com)
  • Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21. (biomedsearch.com)
  • The method according to the invention utilizes biomarkers from blood cells from patients treated with HDAC inhibitors which are easy to assay. (freepatentsonline.com)
  • The canonical Restriction Point model suggests that cells are born into a state in which they are uncommitted to the cell cycle, but will activate cyclin-dependent kinase 2 and cross the Restriction Point several hours later if sufficient nutrients are available. (pnas.org)
  • Together, these data support a model in which only a subset of cells returns to a pre-Restriction Point state after mitosis and where the Restriction Point is sensitive to not only mitogens, but also inherited DNA replication stress via p21. (pnas.org)
  • All but the p53-null cells displayed p53 protein accumulation in a time-dependent manner on noscapine treatment. (aacrjournals.org)
  • P21 is important in the response of cells to genotoxic stress and a major transcriptional target of p53 protein. (thermofisher.com)
  • We isolated CLL cells from the blood of patients before and after short-term treatment with low-dose lenalidomide (5 mg per day) and found the leukemia cells also were induced to express p21 in vivo. (slideshare.net)
  • As they requested, we have presented coimmunoprecipitation data showing endogenous p53-p21 protein interaction in IMR-32 and H460 cells ( Fig. 1 ). (aacrjournals.org)
  • Levels of the p53-p21 complex elevated upon γ-irradiation of H460 cells, consistent with the ability of γ-irradiation to increase p53 and p21 levels. (aacrjournals.org)
  • A and B, Empty or p53 K305N -encoding pcDNA3 vectors and control and p21-targeting siRNAs were introduced into H1299 cells in the indicated combinations. (aacrjournals.org)
  • Mechanisms of MEOX1 and MEOX2 regulation of the cyclin dependent kinase inhibitors p21 and p16 in vascular endothelial cells. (medlineplus.gov)
  • Mixed Lineage Kinase 3 deficiency delays viral clearance in the lung and is associated with diminished influenza-induced cytopathic effect in infected cells. (rochester.edu)
  • Pneumocystis stimulates MCP-1 production by alveolar epithelial cells through a JNK-dependent mechanism. (rochester.edu)
  • Lucilactaene, a New Cell Cycle Inhibitor in p53-Transfected Cancer Cells, Produced by a Fusarium sp. (nii.ac.jp)
  • An antisense construct targeting Bcl-2 or a Bcl-2-specific inhibitor was able to sensitize resistant SCLC cells to RAD001. (aacrjournals.org)
  • Furthermore, it has been found that the ribosomal protein S6 kinases-1 and -2 (S6K1, 2) are highly overexpressed in SCLC cells compared with normal human type II pneumocytes, and that mTOR transduces mitogen-induced proliferation in SCLC ( 6 ). (aacrjournals.org)
  • Historically, it has been difficult to develop small-molecule inhibitors of non-enzyme protein-protein interactions. (sciencemag.org)
  • RAR-beta is a nuclear receptor that bears vitamin-A-dependent transcriptional activity. (genome.jp)
  • PCNA is a co-factor of cyclin-D and it makes a complex with cyclin-D, a cyclin dependent kinase (CDK), and a cyclin dependent kinase inhibitor (CDKI). (biomedcentral.com)
  • To gain an understanding of the precise mechanism by which p21 affects PCNA function, we have designed a new assay for replication factor C (RFC)-catalyzed loading of PCNA onto DNA, a method that utilizes a primer-template DNA attached to agarose beads via biotin-streptavidin. (cshl.edu)
  • rather, p21 formed a stable complex with PCNA on the DNA. (cshl.edu)
  • In contrast, the formation of a p21-PCNA complex on the DNA resulted in the displacement of RFC from the DNA. (cshl.edu)
  • The nonhydrolyzable analogs of ATP, adenosine-5'-O-(3-thiotriphosphate) (ATPgammaS) and adenyl-imidodiphosphate, each stabilized the primer recognition complex containing RFC and PCNA in the absence of p21. (cshl.edu)
  • We propose that p21 stimulates the dissociation of the RFC from the PCNA-DNA complex in a process that requires ATP hydrolysis and then inhibits subsequent PCNA-dependent events in DNA replication. (cshl.edu)
  • Cyclin-dependent kinase inhibitor 1C has been shown to interact with: LIMK1, MYBL2, MyoD, and PCNA. (wikipedia.org)
  • Cell cycle progression is delayed or stopped by cyclin-dependent kinase inhibitors, abbreviated CDIs, CKIs or CDKIs. (wikipedia.org)
  • However, COL1A1 genes were increased by embelin in H 2 O 2 -treated HDFs in a dose-dependent manner. (springer.com)
  • One of the activated genes is an inhibitor of cyclin-dependent kinases. (rcsb.org)
  • In addition, TGF-beta and p53 act through distinct elements in the p21 promoter. (pnas.org)
  • The transforming growth factor-beta responsive element and Sp1 site of the p21 promoter were responsible for the effect of HCV core and HBx, respectively. (nih.gov)
  • Recruitment of JunB to the p21 promoter was promoted by Adriamycin stimulation and was further enhanced by co-treatment with the c-Abl inhibitor imatinib. (biochemj.org)
  • Taken together, these results suggest that, although JunB represses p21 promoter activity, c-Abl phosphorylates JunB and conversely inhibits its suppressive role on p21 promoter activity upon Adriamycin stimulation. (biochemj.org)
  • We recently described p21/p21B status in 73 locally advanced breast cancers ( 15 ), observing no promoter methylation or somatic mutations. (aacrjournals.org)
  • Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. (rcsb.org)
  • Moreover, the overexpression of p21 and p27 inhibits cell proliferation. (elsevier.com)
  • CONCLUSION: Downregulated p21 in PHA stimulated PBL from patients with SLE may be closely related to aberration of cell division in SLE lymphocytes. (jrheum.org)
  • The WST-1 assay demonstrated that decreased cell viability by H 2 O 2 was restored by embelin in a dose-dependent manner. (springer.com)
  • Membrane potential-dependent transport of essential metabolic substrates during the cell cycle and/or volume regulation could also play a role (for review, see Wonderlin and Strobl, 1996 ). (jneurosci.org)
  • Recent work exploring p21 activation in response to DNA damage at a single-cell level have demonstrated that pulsatile p53 activity leads to subsequent pulses of p21, and that the strength of p21 activation is cell cycle phase dependent. (wikipedia.org)
  • Knock down of p21 was effective to sensitize to hunger induced cell loss of life in HCT116 p53? (cell-signaling-pathways.com)
  • Modulation of cyclin accumulation, and thereby Cdk activation, was proposed to be the overarching principle governing the passage through cell cycle phases. (springer.com)
  • The non-receptor-type tyrosine kinase c-Abl functions as a cytoplasmic signal transducer upon activation of cell-surface receptors. (biochemj.org)
  • We have additionally investigated whether p21 influences cell growth under our experimental conditions. (aacrjournals.org)
  • A, IMR-32 cell lysates were immunoprecipitated (IP) using an anti-p21 antibody. (aacrjournals.org)
  • p21 and p53 K305N do not significantly influence cell growth. (aacrjournals.org)
  • Consequently, the functional outcome of TGF-β signalling is strongly context-dependent and is influenced by various factors including cell, tissue and cancer type. (mdpi.com)
  • Based on our data, targeting mTOR by the commercially available and clinically approved inhibitor RAD001 (Everolimus) significantly reduces SCLC cell growth and proliferation. (aacrjournals.org)
  • OBJECTIVE: The roles of cyclins and cyclin dependent kinase (CDK) inhibitors of lymphocytes in the pathogenesis of systemic lupus erythematosus (SLE) are unclear. (jrheum.org)
  • The results further suggest unique roles for Rad5 and abasic endonuclease-dependent DNA intermediates in regulating AFB1-induced mutagenicity. (labome.org)
  • Previously, we demonstrated that the p53/p21 complex promotes Mdm2-dependent Slug ubiquitination and degradation ( 7 ). (aacrjournals.org)
  • N-Terminal ubiquitination of extracellular signal-regulated kinase 3 and p21 directs their degradation by the proteasome. (wikipedia.org)
  • We find that p21 inhibits the activity of each member of the cyclin/CDK family. (nih.gov)
  • The synthesis of another G1 phase cyclin, cyclin E, increases in late G1 and decreases once DNA replication is initiated. (biomedcentral.com)
  • Embelin decreased the SA-β-galactosidase activity in a dose-dependent manner in H 2 O 2 -treated HDFs. (springer.com)
  • Trichocyalides A and B, new inhibitors of alkaline phosphatase activity in bone morphogenetic protein-stimulated myoblasts, produced by Trichoderma sp. (nii.ac.jp)
  • In contrast to DNA damage, however, induction of p21 by TGF-beta is not dependent on wild-type p53. (pnas.org)