Cyclin dependent kinase inhibitor p21. Medical search

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)

p21 is a cyclin-dependent kinase inhibitor. P21 or P-21 may also refer to: p21/ras, part of the RAt Sarcoma family of proteins ... P21), a submarine of the Royal Navy LÉ Emer (P21), a patrol vessel of the Irish Navy Maltese patrol boat P21, of the Armed ... Transforming protein p21, encoded by the HRAS gene in humans ARA King (P-21), a minelayer and patrol ship of the Argentine Navy ... Forces of Malta Curtiss XP-21, an American experimental fighter aircraft P21 road (Ukraine) Papyrus 21, a biblical manuscript ...

https://en.wikipedia.org/wiki/P21_(disambiguation)

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

https://en.wikipedia.org/wiki/P21

"New functional activities for the p21 family of CDK inhibitors". Genes & Development. 11 (7): 847-62. doi:10.1101/gad.11.7.847 ... Cyclin-dependent kinase inhibitor 1C is a tight-binding inhibitor of several G1 cyclin/Cdk complexes and a negative regulator ... Cyclin-dependent kinase inhibitor 1C (p57, Kip2), also known as CDKN1C, is a protein which in humans is encoded by the CDKN1C ... "Entrez Gene: CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2)". Matsuoka S, Edwards MC, Bai C, Parker S, Zhang P, ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_inhibitor_1C

They are p15, p16, p18, p19, p21, p27, and p57. Russo AA, Jeffrey PD, Patten AK, Massagué J, Pavletich NP (July 1996). "Crystal ... A cyclin-dependent kinase inhibitor protein is a protein which inhibits the enzyme cyclin-dependent kinase (CDK). Several ... Seven cyclin-dependent kinase inhibitor proteins have thus far been identified. They are named by the small letter "p" followed ... Cyclin-Dependent+Kinase+Inhibitor+Proteins at the US National Library of Medicine Medical Subject Headings (MeSH) v t e ( ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_inhibitor_protein

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

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_6

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 ...

https://en.wikipedia.org/wiki/DNA_repair

... cyclin-dependent kinase inhibitor". Cancer Research. 64 (5): 1669-1674. 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 ... June 2010). "T-box 2 represses NDRG1 through an EGR1-dependent mechanism to drive the proliferation of breast cancer cells". ...

https://en.wikipedia.org/wiki/TBX2

"The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases". Cell. 75 (4): 805-16. doi:10.1016/ ... Cyclin-dependent kinase 2 has been shown to interact with: BRCA1, CDK2AP1, CDKN1B CDKN3, CEBPA, Cyclin A1, Cyclin E1, Flap ... CDK2 cyclin-dependent kinase 2". Echalier A, Endicott JA, Noble ME (March 2010). "Recent developments in cyclin-dependent ... Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_2

"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 ...

https://en.wikipedia.org/wiki/Wafik_El-Deiry

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 ...

https://en.wikipedia.org/wiki/CDKN3

"P21-activated kinase 4 regulates the cyclin-dependent kinase inhibitor p57(kip2) in human breast cancer". Anatomical Record. ... "Small-molecule p21-activated kinase inhibitor PF-3758309 is a potent inhibitor of oncogenic signaling and tumor growth". ... "p21-activated kinase group II small compound inhibitor GNE-2861 perturbs estrogen receptor alpha signaling and restores ... pyridine-based p21-activated kinase 4 inhibitor". Bioorganic & Medicinal Chemistry Letters. 26 (11): 2580-3. doi:10.1016/j.bmcl ...

https://en.wikipedia.org/wiki/PAK4

Inactivation of cyclin D is triggered by several cyclin-dependent kinase inhibitor protein (CKIs) like the INK4 family (e.g. ... Another way in which DNA damage targets Cdks is p53-dependent induction of p21, which inhibits cyclin E-Cdk2 complex. In ... activate cyclin D gene in response to integrin. p27kip1 and p21cip1 are cyclin-dependent kinase inhibitors (CKIs) which ... Cyclins are eukaryotic proteins that form holoenzymes with cyclin-dependent protein kinases (Cdk), which they activate. The ...

https://en.wikipedia.org/wiki/Cyclin_D

... 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, ...

https://en.wikipedia.org/wiki/TBX3

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 ...

https://en.wikipedia.org/wiki/G-quadruplex

Meis1 has been shown to be necessary for the activation of the cyclin-dependent kinase inhibitors p15, p16, and p21. Knockout ... Cyclin-dependent kinases and cyclin-dependent kinase inhibitors play key roles in this process. One gene, jumonji (jmj), has ... Cardiomyocytes have been shown to be encouraged to exit the cell cycle then cyclin-dependent kinases are downregulated, or when ... of the cardiomyocyte cell cycle is believed to be regulated by transcription factors and cyclin dependent kinase inhibitors, ...

https://en.wikipedia.org/wiki/Cardiomyocyte_proliferation

This includes the cyclin-dependent kinase inhibitor P21 and the tumor suppressor gene Pten to promote neural stem cell ... DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors could possibly reverse epigenetic ... DNMT inhibitors and HDAC often produces antidepressant-like effects. Hu XL, Wang Y, Shen Q (April 2012). "Epigenetic control on ... Although these inhibitors improve some phenotypes of HD in mice, such as neuropathology and motor function, these beneficial ...

https://en.wikipedia.org/wiki/Epigenetic_regulation_of_neurogenesis

... and the cyclin dependent kinase inhibitors P27 and P21". Leuk. Lymphoma. 43 (1): 51-7. doi:10.1080/10428190210195. PMID ... Specifically, TGF-β1 prevents the interleukin(IL)-1- & interleukin-2-dependent proliferation in activated T cells, as well as ... "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. ...

https://en.wikipedia.org/wiki/TGF_beta_1

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 ...

https://en.wikipedia.org/wiki/K562_cells

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 ... Dependent on their relative position to daughter cells on myofibers, satellite cells undergo asymmetric and symmetric division ... Relaix F, Rocancourt D, Mansouri A, Buckingham M (June 2005). "A Pax3/Pax7-dependent population of skeletal muscle progenitor ...

https://en.wikipedia.org/wiki/Myosatellite_cell

"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... Cyclins function as activating subunits of enzymatic complex together with cyclin-dependent kinases (CDKs). Different cyclins ... and the Kip/Cip family of CDK-inhibitor proteins. Cyclin-A1 interacts with: CDC20, Cyclin-dependent kinase 2, E2F1, GNB2L1, ... cyclins and cyclin dependent kinases". Oncogene. 15 (2): 143-157. doi:10.1038/sj.onc.1201252. PMID 9244350. Suzuki Y, Yoshitomo ...

https://en.wikipedia.org/wiki/Cyclin_A1

"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... Cyclin-dependent kinase 7, or cell division protein kinase 7, is an enzyme that in humans is encoded by the CDK7 gene. The ... Cyclin-dependent kinase 7 has been shown to interact with: Androgen receptor, Cyclin H, GTF2H1, MNAT1, P53, SUPT5H, and XPB. ... "Entrez Gene: CDK7 cyclin-dependent kinase 7 (MO15 homolog, Xenopus laevis, cdk-activating kinase)". Patel H, Abduljabbar R, Lai ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_7

"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... "Entrez Gene: CDK4 cyclin-dependent kinase 4". "CDK4 - Cyclin-dependent kinase 4 - Homo sapiens (Human) - CDK4 gene & protein". ... See also CDK inhibitor for inhibitors of various CDKs. Cyclin-dependent kinase 4 has been shown to interact with: CDC37, CDKN1B ... 1995). "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_4

"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, ...

https://en.wikipedia.org/wiki/HIST1H1B

"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, ...

https://en.wikipedia.org/wiki/CDKN2C

"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 ... Yang W, Zhang A, Han Y, Su X, Chen Y, Zhao W (2021). "Cyclin-Dependent Kinase Inhibitor 2b Controls Fibrosis and Functional ...

https://en.wikipedia.org/wiki/CDKN2B

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 JA, Promislow DE (August 2008). "A theory of age-dependent mutation and senescence". Genetics. 179 (4): 2061-2073. doi: ...

https://en.wikipedia.org/wiki/Evolution_of_ageing

... also regulates cell cycle progression by acting on SETD8 to downregulate transcription of cyclin-dependent kinase inhibitor 1 ( ... CDKN1A), also known as p21. CDKN1A binds to and inhibits CDK2 using its N-terminal binding domain, thus blocking progression ... For CDK2 to be activated, cyclin A must bind to the cyclin-dependent kinase complex (CDKC). Cell division cycle 25A (CDC25A) is ... Cyclin-dependent kinases (CDKs) are a family of enzymes that phosphorylate serine and threonine residues to drive the cell ...

https://en.wikipedia.org/wiki/Deubiquitinating_enzyme

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)". Dehkordi, Shiva Kazempour; Walker, Jamie; Sah, ... 1995). "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. ...

https://en.wikipedia.org/wiki/CDKN2D

"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/ ...

https://en.wikipedia.org/wiki/Ed_Harlow

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 ...

https://en.wikipedia.org/wiki/Disposable_soma_theory_of_aging

"A current and comprehensive review of cyclin-dependent kinase inhibitors for the treatment of metastatic breast cancer". ... They halt the cell cycle in G1 phase by binding to and inactivating cyclin-CDK complexes. p21 is activated by p53 (which, in ... Two key classes of regulatory molecules, cyclins and cyclin-dependent kinases (CDKs), determine a cell's progress through the ... cyclin A, DNA polymerase, thymidine kinase, etc. Cyclin E thus produced binds to CDK2, forming the cyclin E-CDK2 complex, which ...

https://en.wikipedia.org/wiki/Cell_cycle

... regulating the cell cycle and cell proliferation by stimulating p21, cFos, Erg-1, and cMyc or inhibiting N-Myc, Cyclin D1, Cdk4 ... "Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IkappaB kinase". Nature. 403 (6765): 103-8. Bibcode: ... DP2 and DP1 are G protein-coupled receptors, with the DP2 receptor coupled to Gi alpha subunit-dependent depression of cellular ... 15-deoxy-Δ12,14-PGJ2 forms an adduct with the IKK-β subunit of IκB kinase thereby inhibiting the kinases activity thereby ...

https://en.wikipedia.org/wiki/Cyclopentenone_prostaglandins

p21 p53 Cyclin-dependent kinase Cyclin D GRCh38: Ensembl release 89: ENSG00000147889 - Ensembl, May 2017 GRCm38: Ensembl ... p16 is also known as: p16INK4A p16Ink4 Cyclin-dependent kinase inhibitor 2A (CDKN2A) CDKN2 CDK 4 Inhibitor Multiple Tumor ... p16 is an inhibitor of cyclin-dependent kinases (CDK). It slows down the cell cycle by prohibiting progression from G1 phase to ... "Entrez Gene: CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)". Nobori T, Miura K, Wu DJ, Lois A, ...

https://en.wikipedia.org/wiki/P16

SKP2 targets p27Kip-1, an inhibitor of cyclin-dependent kinases (CDKs). CDKs2/4 partner with the cyclins E/D, respectively, ... "N-Terminal ubiquitylation of extracellular signal-regulated kinase 3 and p21 directs their degradation by the proteasome". ... This is achieved by continuous control of cyclins or CDKs levels through ubiquitination and degradation. When cyclin E is ... The level of cyclins, as the name suggests, are high only at certain time point during cell cycle. ...

https://en.wikipedia.org/wiki/Ubiquitin

Cyclin D, Cyclin E transcriptional regulators: Myc, E2f1, p130 cyclin-dependent kinase inhibitors (CKIs): p27Kip1, p21, Wee1 ... Schwob, E (1994-10-21). "The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae". Cell. 79 ... βTRCP recognizes these substrates after they are phosphorylated by Polo-like kinase 1 or Cyclin B-CDK1. Fbw7, which is the ... The phenotype was attributed to a failure to degrade Sic1, an inhibitor of S cyclin-CDK complexes. These findings indicated ...

https://en.wikipedia.org/wiki/SCF_complex

Accumulation of cyclin B increases the activity of the cyclin dependent kinase Cdk1 human homolog Cdc2 as cells prepare to ... p53 regulates the function of the Cdk2 inhibitor p21 and the 14-3-3 proteins that phosphorylate (and thereby inactivate) and ... The cell cycle is driven by proteins called cyclin dependent kinases that associate with cyclin regulatory proteins at ... Chk1 is an effector protein kinase that maintains mitotic cyclin in an inactive state and is phosphorylated by rad3 between S ...

https://en.wikipedia.org/wiki/G2-M_DNA_damage_checkpoint

At this point, E2F 1-3 proteins bind to DNA and transcribe Cyclin A and Cdc 6. Cyclin-dependent kinase inhibitor 1B (CDKN1B), ... p53 also transactivates p21, and both p21 and the 14-3-3 in turn inhibit cyclin B-cdc2 complexes through the phosphorylation ... The G1 phase cyclin-dependent kinase works together with S phase cyclin-dependent kinase targeting p27 for degradation. In turn ... Progression through these checkpoints is largely determined by the activation of cyclin-dependent kinases by regulatory protein ...

https://en.wikipedia.org/wiki/Cell_cycle_checkpoint

... 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 ...

https://en.wikipedia.org/wiki/Flap_structure-specific_endonuclease_1

Dutta discovered how the cell cycle factor p21 interacts with and inhibits cyclin-dependent kinases and PCNA, identifying the ... Machida, YJ; Dutta, A (15 January 2007). "The APC/C inhibitor, Emi1, is essential for prevention of rereplication". Genes & ... Takeda, DY; Wohlschlegel, JA; Dutta, A (19 January 2001). "A bipartite substrate recognition motif for cyclin-dependent kinases ... Abbas, T; Sivaprasad, U; Terai, K; Amador, V; Pagano, M; Dutta, A (15 September 2008). "PCNA-dependent regulation of p21 ...

https://en.wikipedia.org/wiki/Anindya_Dutta

... 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 ...

https://en.wikipedia.org/wiki/CDKN1B

... cyclin-dependent kinase inhibitor p19 MeSH D12.776.624.776.355.500 - cyclin-dependent kinase inhibitor p21 MeSH D12.776.624.776 ... cyclin-dependent kinase inhibitor p27 MeSH D12.776.624.776.355.700 - cyclin-dependent kinase inhibitor p57 See List of MeSH ... cyclin-dependent kinase inhibitor p15 MeSH D12.776.624.776.355.200 - cyclin-dependent kinase inhibitor p16 MeSH D12.776.624.776 ... cyclin-dependent kinase 5 MeSH D12.776.167.200.067.900 - cyclin-dependent kinase 9 MeSH D12.776.167.200.580.500 - cdc2 protein ...

https://en.wikipedia.org/wiki/List_of_MeSH_codes_(D12.776)

"Interactions between protein kinase CK2 and Pin1. Evidence for phosphorylation-dependent interactions". The Journal of ... Inhibitors of Pin1 may have therapeutic implications for cancer and immune disorders. The gene encoding Pin1 was identified in ... Wulf GM, Liou YC, Ryo A, Lee SW, Lu KP (Dec 2002). "Role of Pin1 in the regulation of p53 stability and p21 transactivation, ... but protects phosphorylated cyclin D from ubiquitination and proteolysis. Recent data also implicate Pin1 as playing an ...

https://en.wikipedia.org/wiki/PIN1

It specifically recognizes and promotes the degradation of phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also ... such as p27 and p21. Here, SKP2 has been implicated in double negative feedback loops with both p21 and p27, that control cell ... Progression through the cell cycle is tightly regulated by cyclin-dependent kinases (CDKs), and their interactions with cyclins ... "Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated ...

https://en.wikipedia.org/wiki/SKP2

... has been shown to interact with: ARHGEF2, ARPC1B, BMX, C-Raf, CDC42, Cyclin-dependent kinase 5, DYNLL1, LIMK1, NCK1, ... "p21-activated kinase-1 signaling regulates transcription of tissue factor and tissue factor pathway inhibitor". The Journal of ... Shin YJ, Kim YB, Kim JH (September 2013). "Protein kinase CK2 phosphorylates and activates p21-activated kinase 1". Molecular ... "p21-activated kinase-1 signaling mediates cyclin D1 expression in mammary epithelial and cancer cells". The Journal of ...

https://en.wikipedia.org/wiki/PAK1

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 ...

https://en.wikipedia.org/wiki/Arsenic_biochemistry

In addition to p53 and Rb, cyclin dependent kinase inhibitors (CKIs), such as p21, p27, and p57, are also important for ... Immunoprecipitation kinase assays revealed that cyclin C has Rb kinase activity. Furthermore, unlike cyclins D and E, cyclin ... co-immunoprecipitation assays revealed that cyclin-dependent kinase 3 (cdk3) promotes G0 exit by forming a complex with cyclin ... Under normal conditions, the yeast cyclin-dependent kinase complex, Pho80-Pho85, inactivates the Pho4 transcription factor ...

https://en.wikipedia.org/wiki/G0_phase

... 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 ...

https://en.wikipedia.org/wiki/HNRNPK

... is required for activation of a subset of NF-kappaB-dependent genes by recruiting cyclin-dependent kinase 9/cyclin T1 complexes ... "Regulation of NF-κB RelA Phosphorylation and Transcriptional Activity by p21 and Protein Kinase Cζ in Primary Endothelial Cells ... Yang JP, Hori M, Sanda T, Okamoto T (May 1999). "Identification of a novel inhibitor of nuclear factor-kappaB, RelA-associated ... TANK-binding kinase-1 (TBK1) and TRAF2-associated kinase (T2K)). The fact that RELA can be modified by a collection of kinases ...

https://en.wikipedia.org/wiki/RELA

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

https://en.wikipedia.org/wiki/Histone_acetylation_and_deacetylation

S interface of the cell cycle by modulating cyclin-dependent inhibitory kinase (CKI) pathways. The OGF-OGFr axis is a tonically ... Cyclin-Dependent Kinase Inhibitor p16 / metabolism * Cyclin-Dependent Kinase Inhibitor p21 / metabolism ... S interface of the cell cycle by modulating cyclin-dependent inhibitory kinase (CKI) pathways. The OGF-OGFr axis is a tonically ... Cyclin-Dependent Kinase Inhibitor p16 * Cyclin-Dependent Kinase Inhibitor p21 * Narcotic Antagonists ...

https://pubmed.ncbi.nlm.nih.gov/22687282/

... p21, inhibitor of cyclin-dependent kinases. ... PIP3 is generated as a result of BCR-dependent PI3K activation ... Following signaling via the BCR, protein kinase C (PKC) beta-dependent serine phosphorylation within the CARD11 linker domain ... PI3K, phosphatidylinositide-3 kinase; AKT, protein kinase B; PTEN, phosphatase and tensin homolog; PIP2, phosphatidylinositol-4 ... 10] Alternatively, activation of NFkB results from the proteasome degradation of its inhibitor (inhibitor of kappa B [IkB]). ...

https://www.medscape.com/answers/202969-188120/what-is-included-in-patient-education-about-diffuse-large-b-cell-lymphoma-dlbcl

... p21, inhibitor of cyclin-dependent kinases. ... PIP3 is generated as a result of BCR-dependent PI3K activation ... PI3K, phosphatidylinositide-3 kinase; AKT, protein kinase B; PTEN, phosphatase and tensin homolog; PIP2, phosphatidylinositol-4 ... B-cell receptor signaling activates PI3K-mediated activation of the kinase AKT, which activates many downstream signaling ... usually anaplastic lymphoma kinase [ALK]) positive). [49] While each of these variants can be determined by pathological ...

https://emedicine.medscape.com/article/202969-workup

Cyclin-Dependent Kinase Inhibitor p21. Nian H, Delage B, Pinto JT, Dashwood RH. 2008. Allyl mercaptan, a garlic-derived ...

https://lpi.oregonstate.edu/biblio?f%5Bauthor%5D=5541&o=asc&s=keyword

Tbx2 directly represses the expression of the p21(WAF1) cyclin-dependent kinase inhibitor. Prince, S., Carreira, S., Vance, K. ... The long non-coding RNA Paupar promotes KAP1-dependent chromatin changes and regulates olfactory bulb neurogenesis. Pavlaki, I. ...

https://researchportal.bath.ac.uk/en/persons/keith-vance/publications/?ordering=title&descending=false

Mechanisms of MEOX1 and MEOX2 regulation of the cyclin dependent kinase inhibitors p21 and p16 in vascular endothelial cells. ...

https://medlineplus.gov/genetics/gene/meox1/

The cyclin-dependent kinase inhibitor p21 is induced by both p53-dependent and p53-independent mechanisms and can arrest the ... "The role of the cyclin-dependent kinase inhibitor p21 in apoptosis". Molecular Cancer Therapeutics. 1 (8): 639-49. PMID ... cell cycle at the G1/S and G2/M checkpoints by deactivating cyclin/cyclin-dependent kinase complexes.[57] ... Checkpoint Proteins can be separated into four groups: phosphatidylinositol 3-kinase (PI3K)-like protein kinase, proliferating ...

https://en.m.wikipedia.org/wiki/DNA_repair

... such as platinum chemotherapy and PARP inhibitors. Olaparib is currently indicated for maintenance therapy in metastatic PDAC ... p53 is needed to activate p21, a cyclin-dependent kinase inhibitor, which induces the G1-S checkpoint arrest. A depletion in ... Thus, WEE1 kinase inhibitors are salient partners for platinum chemotherapy [109]. A study by Hartman and colleagues analyzed a ... PARP Inhibitors in Combination with Other Agents. PARP inhibitors have also been tested in the combination setting in BRCA- ...

https://www.mdpi.com/2072-6694/14/10/2453

p53 is a transcription factor for Waf-1/p21, a cyclin-dependent kinase inhibitor. Certain polymorphic variants of Waf-1 and p53 ...

http://www2a.cdc.gov/nioshtic-2/BuildQyr.asp?s1=genetic&f1=TI&Startyear=&t1=1&s2=genetic&terms=3&Adv=1&ct=&B1=Search&f2=KW&Limit=500&Sort=DP+DESC&D1=10&EndYear=&PageNo=52&RecNo=519&View=f&

The cyclin-dependent kinase inhibitor p21 is an important player in stress pathways exhibiting both tumor-suppressive and ... Nucleolar GTP-binding Protein-1 (NGP-1) Promotes G1 to S Phase Transition by Activating Cyclin-dependent Kinase Inhibitor p21 ... CDK inhibitor, p21, enhances cell proliferation in certain situations.Significance: This study provides evidence that p21 ... Although tyrosine kinase inhibitors provide an effective treatment for these diseases, they generally do not kill leukemic stem ...

https://www.jbc.org/Gene-Regulation?startPage=&KeywordRaw=p53

Luminal cells expressed negative regulators of the cell cycle, including the cyclin-dependent kinase inhibitors p21CIP1/WAF1 ( ... The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75: 805-816 ... RNase inhibitor (Roche Diagnostics Ltd, Burgess Hill, UK) was used at a concentration of 0.5 U μl−1 in all solutions. ... Thien CB, Langdon WY (2001) Cbl: many adaptations to regulate protein tyrosine kinases. Nat Rev Mol Cell Biol 2: 294-307 ...

https://www.nature.com/articles/6604774?error=cookies_not_supported

These data were supported by an increase in the cyclin-dependent kinase inhibitor p21 (Supplemental Figure 6E) associated with ... This FXN-dependent effect was robustly increased with hydroxyurea, a ribonucleotide reductase inhibitor that depletes ... While certain FXN-dependent phenotypes share similarities with those resulting from deficiencies of other HIF-α-dependent Fe-S ... First, tamoxifen-dependent endothelial (EC) Fxn-/- mice (Cdh5(PAC)-Cre-ERT2+ mice [71] crossed with Fxn flox/flox mice; ref. 72 ...

https://www.jci.org/articles/view/136459

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 ... Channels and Membrane Depolarization Regulate Accumulation of the Cyclin-Dependent Kinase Inhibitors p27Kip1 and p21CIP1 in ...

https://www.jneurosci.org/content/19/13.index-by-author

Androgen induction of cyclin-dependent kinase inhibitor p21 gene: role of androgen receptor and transcription factor Sp1 ... Androgen regulation of the cyclin-dependent kinase inhibitor p21 gene through an androgen response element in the proximal ... Elevated cyclins and cyclin-dependent kinase activity in the rhabdomyosarcoma cell line RD. Cancer Res ... It has been shown by our group and others that androgen induces accumulation of cyclin D1, cyclin A, and p21cip1 in LNCaP cells ...

https://aacrjournals.org/cancerres/article/65/1/54/517917/Xenoestrogen-Action-in-Prostate-Cancer-Pleiotropic

Injection of the cdk (cyclin-dependent kinase) inhibitor p21 into one blastomere of a dividing embryo blocks centrosome ... Cyclin-dependent kinase control of centrosome duplication PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES ... Cyclin-dependent kinase control of motile ciliogenesis ELIFE Vladar, E. K., Stratton, M. B., Saal, M. L., Salazar-De Simone, G ... depletion of either cdk2 or of the two activating cyclins, cyclin A and cyclin E, eliminates centriole separation activity. In ...

https://profiles.stanford.edu/tim-stearns

NM_000389.1 cyclin-dependent kinase inhibitor 1A (p21, Cip1) 1.3 9.8 8.6 1.0 2.0 2.0 1.0 8.0 7.5 ... AB012305.1 cyclin-dependent kinase 2 -1.7 -3.5 -5.3 -2.0 -2.1 -2.1 NC -2.8 -3.5 ... AF112857.1 cyclin E2 splice variant 1 mRNA 1.2 -3.5 -3.2 NC -2.0 -1.6 -1.4 -7.0 -8.6 ... NM_001237.1 cyclin A2 (CCNA2) -1.2 -5.7 -12.1 NC NC -2.1 -1.1 -8.6 -13.9 ...

https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-5-7/tables/3

Induction of the cyclin-dependent kinase inhibitor p21(Sdi1/Cip1/Waf1) by nitric oxide-generating vasodilator in vascular ... Inhibitors of the proteasome block the myogenic differentiation of rat L6 myoblasts. 1998, Pubmed Kuzin, Nitric oxide regulates ... NF-kappaB-dependent expression of nitric oxide synthase is required for membrane fusion of chick embryonic myoblasts. 1997, ... Nitric oxide synthase inhibitors attenuate transforming-growth-factor-beta 1-stimulated capillary organization in vitro. 1997, ...

https://www.xenbase.org/entry/literature/article.do?method=display&articleId=8126

In conclusion, we for the first time demonstrated that hinokitiol upregulates p21 expression and attenuates IFN-,i,γ,/i, ... and Cdk4 expression and upregulated p21 expression. These results revealed that hinokitiol may regulate immune responses. ... In addition, hinokitiol also downregulated cyclin D3, E2F1, ... "Role of cyclin kinase inhibitor p21 in systemic autoimmunity," ... The cell cycle inhibitor p21, which belongs to the Cip/Kip family, interferes with cycling by inhibiting all cyclin-dependent ...

https://www.hindawi.com/journals/ecam/2015/595824/

Taken together, these results implicate Tbx2 as a novel direct regulator of p21 expression and have implications for our ... The p21WAF1 cyclin-dependent kinase inhibitor plays a key role in senescence and in cell cycle arrest after DNA damage. Here, ... Moreover, small interfering RNA-mediated down-regulation of Tbx2 expression results in a robust activation of p21 expression. ... we show that Tbx2 can bind and repress the p21 promoter in vitro and in vivo. ...

https://www.ndm.ox.ac.uk/publications/92996

ATM and p53 relay a signal that causes the induction of a family of inhibitors of cyclin dependent kinases (including p21 and ... While some genetic expression or lack thereof in senescence are dependant on the type of cell involved, ie; cd28 in T cells and ... However most of the genetic changes like the expression of ATM, p53, P21 and P16 as well as other biochemicals like ...

http://www.bio.net/bionet/mm/ageing/1998-September/003336.html

... in part by inducing transcription of genes such as CDKN1A encoding the inhibitor of G1 cyclin-dependent kinases, p21CIP1, thus ... Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase ... The Ca2+/calmoldulin-dependent protein kinase kinases are AMP-activated protein kinase kinases ... Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells ...

https://portlandpress.com/biochemj/article/479/22/2327/232102/AMP-activated-protein-kinase-a-journey-from-1-to?searchresult=1

The cyclin-dependent kinase inhibitor p21 limits murine mesangial proliferative glomerulonephritis. Monkawa, T., Pippin, J., Yo ...

https://keio.pure.elsevier.com/en/publications/?page=1543&ordering=type&descending=true&showAdvanced=false&allConcepts=true&inferConcepts=true&originalSearch=&improvedLayoutOrganisationUuid=&format=

... was not dependent on the cyclin dependent kinase inhibitor p21WAF1/CIP1, rather it was associated with an upregulation of p- ... 5023), cyclin D1 (catalog no. 2978), cyclin B1 (catalog no. 12231), phosphorylated (p)-cyclin dependent kinase 2 (p-Cdc2Tyr15; ... phosphorylated cyclin dependent kinase 2; PE, phycoerythrin; SFN, sulforaphane. ... phosphorylated-cyclin dependent kinase 2; PE, phycoerythrin; SFN, sulforaphane. ...

https://www.spandidos-publications.com/10.3892/mmr.2017.6789

... and by negatively regulating the cyclin-dependent kinase inhibitors p27 Kip1 (15) and p21 Waf1/Cip1 (16). Akt also plays a ... LY294002 is a specific PI3 kinase inhibitor (11). Another essential Akt function is the regulation of glycogen synthesis ... Akt, also referred to as PKB or Rac, plays a critical role in controlling survival and apoptosis (1-3). This protein kinase is ... an inhibitor of mTOR within the mTOR-raptor complex (18,19).. * Franke, T.F. et al. (1997) Cell. 88, 435-7. ...

https://www.cellsignal.com/products/elisa-kits/total-akt2-sandwich-elisa-kit-mouse-preferred/7930?N=102262+4294964832+4294956287&fromPage=plp

Transcriptional repression of cyclin-dependent kinase inhibitor p21 gene by phospholipase D1 and D2. Kwun, H. J., Lee, J. H., ... Transcriptome analysis of IBET-151, a bet inhibitor alone and in combination with paclitaxel in gastric cancer cells. Kang, S. ...

https://yonsei.pure.elsevier.com/en/publications/?showAdvanced=false&allConcepts=true&inferConcepts=true&publicationYear=2018&publicationYear=2019&publicationYear=2020&publicationYear=2021&author=ef803592-5a7c-4c84-9732-79f8ef7f3679&format=&nofollow=true&ordering=type&descending=true&page=1637

The proliferation-inhibiting and apoptosis-inducing effects of Haelan are highly dependent on cell type and concentration ... and its anticancer activity may be potentiated when administered with calpain inhibitors. ... We investigated the effects of the isoflavone containing beverage Haelan 951 and the calpain inhibitor PD150606 on the ... the protease cleaves inhibitors of cyclin-dependent kinases p21/Cip1 and p27/Kip1, which in turn facilitates cell proliferation ...

https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-015-0734-0

... followed by the genes encoding phosphoglycerate kinase 1 (PGK1) and succinate dehydrogenase complex subunit A (SDHA). A careful ... One of P53s most important transcriptional targets is the cyclin-dependent kinase inhibitor p21, which can provoke cell-cycle ... namely phospho-inositide kinases, check point kinases 1 and 2 and the group of BRCT (breast cancer C-terminal repeats) proteins ... Garrido C, Schmitt E, Candé C, Vahsen N, Parcellier A, Kroemer G: HSP27 and HSP70: potentially oncogenic apoptosis inhibitors. ...

https://bmcresnotes.biomedcentral.com/articles/10.1186/1756-0500-6-264

... p21 is a potent cyclin-dependent kinase inhibitor that can stabilize the interaction between cyclin-dependent kinase (CDK)-4/6 ... cyclin-dependent kinase; HDACi: Histone deacetylase inhibitors.. Authors contributions. Conceptualization and methodology: CL ... and cyclin D and promote the formation of cyclin D/CDK complexes. Overexpression of p21 leads to the arrest of cells in the G1/ ... Histone deacetylase inhibitor, Romidepsin (FK228) inhibits endometrial cancer cell growth through augmentation of p53-p21 ...

https://www.researchsquare.com/article/rs-50247/v1

... cells in the G0/G1 phase of the cell cycle and induced the expression of the cyclin-dependent rotein kinase inhibitor p21. ... Furthermore local perivascular application of the potent and selective rginase inhibitors S-(2-boronoethyl)-L-cysteine (BEC) or ...

http://libres.uncg.edu/ir/listing.aspx?id=13805

The cyclin-dependent kinase inhibitor p21 is regulated by RNA-binding protein PCBP4 via mRNA stability Chen, X, Cho, SJ, ... Transcriptional activation of cell cycle inhibitor p21 (Homo sapiens) * PCBP4 binds the CDKN1A mRNA (Homo sapiens) * PCBP4: ... p53-Dependent G1/S DNA damage checkpoint (Homo sapiens) * p53-Dependent G1 DNA Damage Response (Homo sapiens) * Transcriptional ...

https://reactome.org/content/detail/R-HSA-6803405

In addition, hinokitiol also downregulated cyclin D3, E2F1, and Cdk4 expression and upregulated p21 expression. (hindawi.com)

A casual decision made one evening in 1976, in a bar near the Biochemistry Department at the University of Dundee, led me to start my personal research journey by following up a paper that suggested that acetyl-CoA carboxylase (ACC) (believed to be a key regulatory enzyme of fatty acid synthesis) was inactivated by phosphorylation by what appeared to be a novel, cyclic AMP-independent protein kinase. (portlandpress.com)
This led me to define and name the AMP-activated protein kinase (AMPK) signalling pathway, on which I am still working 46 years later. (portlandpress.com)
Moreover, gene and protein expression analyses suggested that this effect was achieved through the regulation of p21 and p53 expression. (researchsquare.com)
Moreover treatment of VSMCs with BEC or L-OHNA or knockdown of arginase I protein rrested cells in the G0/G1 phase of the cell cycle and induced the expression of the cyclin-dependent rotein kinase inhibitor p21. (uncg.edu)
Protein kinase A-induced phosphorylation of Sox9 enhances Sox9-dependent transcription by increasing the DNA-binding aﬃnity of Sox9. (heightquest.com)
CHIR-99021 is a GSK-3α/β inhibitor with an IC50 of 10 and 6.7 nM，showing 500-fold selectivity over its closest homologs CDC2 and ERK2, as well as other protein kinases. (dcchemicals.com)

APE1 was earlier shown to stimulate p53's DNA binding and its transactivation function in the expression of cyclin-dependent kinase inhibitor p21 (CDKN1A) gene. (nebraska.edu)

The resulting free Sp1/3 transcriptionally activated p21 CIP1/WAF1 , a representative negative regulator of cell growth. (rupress.org)

Using 20 epidermal biopsies from blue, fin and sperm whale, we found that the genes encoding the ribosomal proteins L4 and S18 ( RPL4 and RPS18 ) were the most suitable to use as controls, followed by the genes encoding phosphoglycerate kinase 1 ( PGK1 ) and succinate dehydrogenase complex subunit A ( SDHA ). (biomedcentral.com)
Although the identities of the sensors are still unclear, transducers include four sets of conserved proteins, namely phospho-inositide kinases, check point kinases 1 and 2 and the group of BRCT (breast cancer C-terminal repeats) proteins [ 7 ]. (biomedcentral.com)
Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (prospecbio.com)

Background: The cyclin-dependent kinase inhibitor p21CIP1/WAF1 is involved in cell-cycle growth arrest due to cell stressors, such as cigarette smoke. (elsevier.com)

Although tyrosine kinase inhibitors provide an effective treatment for these diseases, they generally do not kill leukemic stem cells (LSCs), the cancer-initiating cells that compete with normal hematopoietic stem cells for the bone marrow niche. (jbc.org)
Increased expression and/or activation of the tyrosine kinase c-Src has classically been associated with increased aggressiveness in cancer cells. (virginia.edu)

We also show that higher concentrations of BPA block proliferation of AR-positive, androgen-dependent prostate adenocarcinoma cells (LNCaP and LAPC-4), with a more modest inhibitory effect on androgen-independent cells (22Rv-1). (aacrjournals.org)
The cell cycle inhibitor p21, which belongs to the Cip/Kip family, interferes with cycling by inhibiting all cyclin-dependent kinases (CDKs) involved in the G1/S phase, thereby controlling cell proliferation and tumorigenesis in various cell types [ 4 ]. (hindawi.com)
In addition, p21 deficiency was reported to enhance T lymphocyte activation and proliferation and to induce autoimmune manifestations [ 5 ]. (hindawi.com)
Suppression of p21 promotes malignant T lymphocyte proliferation in malignant CD30 + T lymphocytes [ 6 ]. (hindawi.com)
Thus, p21 may play a critical role in autoimmune diseases and tumorigenesis by regulating T lymphocyte activation and proliferation. (hindawi.com)
The proliferation-inhibiting and apoptosis-inducing effects of Haelan are highly dependent on cell type and concentration administered. (biomedcentral.com)
In the present study, we investigated whether, in the epithelium of small airways of smokers with and without COPD, altered p21 expression is associated with an imbalance between proliferation and apoptosis. (elsevier.com)
Objectives and Methods: The expression of specific molecules involved in the regulation of apoptosis, such as activated caspase-3 and cytoplasmic p21, cell quiescence (G0) or proliferation markers such as Ki67 and PCNA, and cell-cycle markers such as the nuclear p21, was assessed in the small airway (bronchiolar) epithelium of smokers with and without COPD and in nonsmoker non-COPD subjects. (elsevier.com)
Furthermore, p21 alteration may be associated with the inhibition of tissue repair in smokers and smokers with COPD as confirmed by the low expression of proliferation markers such as PCNA. (elsevier.com)
It is thus likely that APE1 overexpression and inactivation of p53, often observed in tumor cells, promote tumor cell proliferation by constitutively downregulating p21 expression. (nebraska.edu)
Interestingly, it was demonstrated that c-Src expression in the UMUC3 cell iii line had a direct correlation with p21 expression suggesting that c-Src could act as a suppressor of proliferation in UC via increased p21 expression. (virginia.edu)

Cyclin-dependent kinase inhibitor p21 dysregulation induces oligodendrocyte differentiation impairment in multiple sclerosis cerebral organoids. (tischms.org)

Nanomicelles Potentiate HDAC Inhibitor Efficacy In Vitro. (researchsquare.com)
Based on histone deacetylation phenotypes implied by bioinformatic analysis, HDAC inhibitors demonstrated significant survival superiority in the survival of TR mice, yielding insights into clinical efficacy against rare types of APL. (bvsalud.org)

Waf-1 (p21) and p53 polymorphisms in breast cancer. (cdc.gov)
Polymorphisms of p21 cyclin-dependent kinase inhibitor and malignant skin tumors. (cdc.gov)

Here, using a combination of in vitro DNA-binding, transfection, and chromatin immunoprecipitation assays, we show that Tbx2 can bind and repress the p21 promoter in vitro and in vivo. (ox.ac.uk)
CHIR-99021 is a glycogen synthase kinase 3 beta inhibitor that has antiproliferative activity in vitro and in vivo. (dcchemicals.com)
CHIR 99021 is a small organic molecule that inhibits GSK3α and GSK3β by competing for their ATP-binding sites.In vitro kinase assays reveal that CHIR 99021 specifically inhibits GSK3β (IC50=~5 nM) and GSK3α (IC50=~10 nM), with little effect on other kinases[2]. (dcchemicals.com)

SFN has also been reported to sensitize cancer cells to imatinib- and tumor necrosis factor-related apoptosis inducing ligand-induced apoptosis, via a reactive oxygen species (ROS)-dependent pathway ( 8 , 9 ), suggesting potential therapeutic value as an adjunct to current cancer therapies. (spandidos-publications.com)
We investigated the effects of the isoflavone containing beverage Haelan 951 and the calpain inhibitor PD150606 on the viability, growth and apoptosis of the human pancreatic cancer cell lines CAPAN-1 and BxPC-3, on the rat pancreatic cancer cell line AR42J, and on human fibroblasts as the control cell line. (biomedcentral.com)
The role of p21 in cell apoptosis is controversial as it exerts pro-or antiapoptotic effects in different cells. (elsevier.com)
Moreover, aged ASCs were characterized by increased gene expression of pro-inflammatory cytokines and miRNAs (interleukin 8 (IL-8), IL-1β, tumor necrosis factor α (TNF-α), miR-203b-5p, and miR-16-5p), as well as apoptosis markers (p21, p53, caspase-3, caspase-9). (biomedcentral.com)

Moreover, blocking AKT or STAT3 pathway with a specific inhibitor could partially reverse the promotion of melanoma malignancy mediated by TRIM14 overexpression. (aging-us.com)
BIO (6-bromoindirubin-3'-oxime) is a specific inhibitor of GSK-3 with IC50 of 5 nM for GSK-3α/β, shows >16-fold selectivity over CDK5, also a pan-JAKinhibitor. (dcchemicals.com)

In this study, Pluronic F127 was used to fabricate nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigenetic-driven anti-cancer effect in several tumor types. (researchsquare.com)
the BMP-2 inhibitor Noggin represses Sox9 expression in limb bud chondrogenic precursors while inducing the ligament/tendon-speciﬁc transcription factor Scx" "the histone acetyltransferase (HAT) activity of p300 has the potential to facilitate transcriptional activity by modulating the chromatin structure. (heightquest.com)

Furthermore local perivascular application of the potent and selective rginase inhibitors S-(2-boronoethyl)-L-cysteine (BEC) or NG-hydroxy-nor-L-arginine (L-OHNA) mmediately after injury markedly attenuated medial and neointimal DNA synthesis and neointima ormation. (uncg.edu)
SB 216763 is a potent and selective cell permeable ATP-competitive inhibitor of GSK3α with an IC50 value of 34 nM (similar potency for GSK3β). (dcchemicals.com)
CP21R7 is a potent and selective GSK-3β inhibitor. (dcchemicals.com)

In conclusion, we for the first time demonstrated that hinokitiol upregulates p21 expression and attenuates IFN- γ secretion in ConA-stimulated T lymphocytes, thereby arresting cell cycle at the G0/G1 phase. (hindawi.com)

Sox9 interacts with the Med12/Trap230 subunit of the mediator complex to stimulate RNA polymerase II-dependent transcription in chondrocytes. (heightquest.com)

The p21WAF1 cyclin-dependent kinase inhibitor plays a key role in senescence and in cell cycle arrest after DNA damage. (ox.ac.uk)
Taken together, these results implicate Tbx2 as a novel direct regulator of p21 expression and have implications for our understanding of the role of T-box factors in the regulation of senescence and oncogenesis, as well as in development. (ox.ac.uk)
However most of the genetic changes like the expression of ATM, p53, P21 and P16 as well as other biochemicals like collagenases an cd28 have been directly related to the cells entrance into the G1 block of senescence. (bio.net)

The opioid growth factor (OGF), chemically termed [Met(5)]-enkephalin, is an endogenous opioid peptide that interacts with the OGF receptor (OGFr) to delay the G(1)/S interface of the cell cycle by modulating cyclin-dependent inhibitory kinase (CKI) pathways. (nih.gov)

Results: In smokers with and without COPD, we found an increase of cytoplasmic nuclear p21 and activated caspase-3 expression. (elsevier.com)
Conclusions: In the small airway epithelium, cytoplasmic p21 correlating with increased activated caspase-3 expression might play a proapoptotic role. (elsevier.com)

We then identified APE1's another binding site in p21's proximal promoter region containing cis elements for AP4, a repressor of p21. (nebraska.edu)
Moreover, ectopic p53 in p53-null cells inhibited AP4's association with APE1, their binding to the promoter and p21 repression. (nebraska.edu)

The rate of DNA repair is dependent on many factors, including the cell type, the age of the cell, and the extracellular environment. (wikipedia.org)
We have shown that duplication of the centrosome, the microtubule organizing center of animal cells, is dependent on the cell cycle kinase cdk2, and on cell cycle-specific proteolysis. (stanford.edu)
293 cells were transfected with XNOS cDNA, and the NOS activity in the cell extract was measured using the arginine-to-citrulline conversion assay in the presence or absence of various cofactors and inhibitors. (xenbase.org)

Ectopic expression of p53 in the p53-null cells abrogated this repression suggesting that APE1's negative regulatory role in p21 expression is dependent on the p53 status. (nebraska.edu)
Importantly, these data also suggested that c-Src inhibitors would be contraindicated in UC patients with high cSrc expression. (virginia.edu)
Thus, while c-Src is likely important in regulating p21 expression in UC, the phenotypic impact of this relationship is likely subtle. (virginia.edu)

p53 is a transcription factor for Waf-1/p21, a cyclin-dependent kinase inhibitor. (cdc.gov)
Several transcription factors and coactivators, such as Scleraxis/E47 and p300, cooperatively modulate the Sox9-dependent transcription by interacting with Sox9. (heightquest.com)
The TGF-β-regulated Smad3/4 complex activates Sox9-dependent transcription on chromatin by associating with Sox9 itself, and by recruiting p300 onto Sox9 [thus TGF-Beta may help with Sox9 transcription, note LSJL increases TGF-Beta levels]. (heightquest.com)

no significant inhibition on 26 other kinases. (dcchemicals.com)

The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (prospecbio.com)

Here, we show APE1's stable binding to p53 cis elements which are required for p53-mediated activation of p21 in p53-expressing wild type HCT116 cells. (nebraska.edu)

These results together establish APE1's role as a co-activator or co-repressor of p21 gene, dependent on p53 status. (nebraska.edu)

The results show for the first time that Haelan may be a promising candidate in the treatment of human pancreatic cancer, and its anticancer activity may be potentiated when administered with calpain inhibitors. (biomedcentral.com)

The overall effects of impaired calcium extrusion due to age-dependent decline of PMCA function seem to accumulate with age, increasing the susceptibility to neurotoxic insults. (transhumanist.ru)

The operational activities of cells are based on an awareness of their current state, coupled to a programmed response to internal and external cues in a context-dependent manner. (tamu.edu)
Loss of BAF180 blunts the induction of the canonical p53 target p21, which functions as a cyclin-dependent kinase inhibitor, in response to particular forms of stress. (ees2010prague.org)

Mechanisms of MEOX1 and MEOX2 regulation of the cyclin dependent kinase inhibitors p21 and p16 in vascular endothelial cells. (medlineplus.gov)
However, surprisingly, we observed APE1-dependent repression of p21 in isogenic p53-null HCT116 cells. (nebraska.edu)

Diffuse Large B-Cell Lymphoma (DLBCL): Practice Essentials, Background, Pathophysiology (medscape.com)

Diffuse Large B-Cell Lymphoma (DLBCL) Guidelines: Guidelines Summary (medscape.com)

Diffuse Large B-Cell Lymphoma (DLBCL) Workup: Approach Considerations, Flow Cytometry and Genetic Studies, Imaging Studies (medscape.com)

Keith Vance - Research output

- the University of Bath's research portal — Keith Vance - Research output - the University of Bath's research portal (researchportal.bath.ac.uk)

MEOX1 gene: MedlinePlus Genetics (medlineplus.gov)

Cancers | Free Full-Text | BRCA-Mutated Pancreatic Cancer: From Discovery to Novel Treatment Paradigms (mdpi.com)

Sci. Pharm. | Free Full-Text | Anti-Proliferative and Genotoxic Activities of the Helichrysum petiolare Hilliard & B.L.... (mdpi.com)

TEAD1 and c-Cbl are novel prostate basal cell markers that correlate with poor clinical outcome in prostate cancer | British... (nature.com)

JCI -
Frataxin deficiency promotes endothelial senescence in pulmonary hypertension — JCI - Frataxin deficiency promotes endothelial senescence in pulmonary hypertension (jci.org)

Index by author - July 01, 1999, 19 (13) | Journal of Neuroscience (jneurosci.org)

Xenoestrogen Action in Prostate Cancer: Pleiotropic Effects Dependent on Androgen Receptor Status | Cancer Research | American... (aacrjournals.org)

Tim Stearns' Profile | Stanford Profiles (profiles.stanford.edu)

Anatomy7

Organisms2

Chemicals and Drugs72

Analytical, Diagnostic and Therapeutic Techniques and Equipment5

Phenomena and Processes29

Disciplines and Occupations1

Information Science3

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

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

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

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

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

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

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

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

Cyclin-Dependent Kinase Inhibitor p27

Cyclin-Dependent Kinase Inhibitor p21

Cyclin-Dependent Kinases

Cyclins

Cell Cycle Proteins

Cyclin-Dependent Kinase Inhibitor p16

Cell Cycle

Tumor Suppressor Proteins

Microtubule-Associated Proteins

Cyclin-Dependent Kinase 2

Cyclin D1

Cyclin A

Cyclin E

Cell Proliferation

Cyclin-Dependent Kinase 4

CDC2-CDC28 Kinases

Apoptosis

Cyclin-Dependent Kinase Inhibitor p57

Cell Line, Tumor

Protein Kinase Inhibitors

Protein-Serine-Threonine Kinases

G1 Phase

Cyclin-Dependent Kinase 5

Cyclin B

Cyclin D

CDC2 Protein Kinase

Cyclin-Dependent Kinase Inhibitor Proteins

Cyclin C

Phosphorylation

Cyclin D3

Retinoblastoma Protein

Cyclin-Dependent Kinase 6

Cell Division

Enzyme Inhibitors

S Phase

Cyclin B1

Cyclin-Dependent Kinase Inhibitor p18

Tumor Suppressor Protein p53

Proto-Oncogene Proteins

Tumor Cells, Cultured

Signal Transduction

Cyclin D2

Cells, Cultured

Phosphatidylinositol 3-Kinases

Blotting, Western

E2F1 Transcription Factor

Cyclin A1

Protein Kinases

Purines

Transfection

Cell Line

Mitosis

Cyclin G

G2 Phase

Transcription Factor DP1

Mutation

Proliferating Cell Nuclear Antigen

Cyclin-Dependent Kinase Inhibitor p15

DNA-Binding Proteins

Cyclin G1

MAP Kinase Signaling System

Cyclin A2

E2F Transcription Factors

RNA, Messenger

Molecular Sequence Data

Carrier Proteins

Nuclear Proteins

Antineoplastic Agents

Transcription Factors

Base Sequence

Protein-Tyrosine Kinases

Calcium-Calmodulin-Dependent Protein Kinases

Immunohistochemistry

Cyclin-Dependent Kinase Inhibitor p19

S-Phase Kinase-Associated Proteins

src-Family Kinases

Enzyme Activation

Down-Regulation

Gene Expression Regulation

Protein Binding