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.

Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. (1/73)

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)

Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity. (2/73)

Cell cycle regulatory proteins are important candidates for therapeutic tumour suppressors. Adenovirus vectors were constructed to overexpress cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 under the control of the murine cytomegalovirus immediate early gene promoter. These vectors directed the efficient expression of each of the cyclin kinase inhibitors and induced growth arrest, inhibited DNA synthesis, and prevented phosphorylation of the retinoblastoma protein (pRb) in cell lines expressing functional pRb. In pRb-deficient cells, expression of the cyclin kinase inhibitors was not effective in inhibiting DNA replication or growth arrest. Interestingly, three of the cyclin kinase inhibitors, p16, p18 and p27 were found to induce apoptotic death in transduced HeLa and A549 cells. When the vectors were tested for their ability to inhibit tumorigenicity in a polyomavirus middle T antigen model of murine breast carcinoma, expression of the cyclin kinase inhibitors resulted in a delay in tumour formation that varied from several weeks for the p19 expressing vector to greater than 25 weeks for the p27 expressing vector. When tumours were injected directly with the adenovirus vectors expressing the cyclin kinase inhibitors, only treatment with the vector expressing p16 resulted in a delay in tumour growth.  (+info)

Mutation testing in melanoma families: INK4A, CDK4 and INK4D. (3/73)

The INK4A gene which codes for the cyclin-dependent kinase (CDK) inhibitor INK4A or p16 underlies susceptibility to melanoma in some families. Germline mutations in the gene that codes for the target protein of p16, CDK4, underlie susceptibility in very rare families. We report mutation screening of the INK4A and CDK4 genes in 42 UK families. A total of nine families were identified with INK4A mutations and none with CDK4 exon 2 mutations. These mutations were in 8/22 (35%) families with three or more cases of melanoma and 1/20 (5%) families with only two cases. In one of these nine families a novel single base pair substitution was identified, Gly67Arg. In an attempt to identify another melanoma susceptibility gene, a member of the INK4 family, the p19 INK4D gene has been studied. The p19 gene was sequenced in DNA from the 42 UK families and six additional US families. No mutations were identified.  (+info)

Postnatal neuronal proliferation in mice lacking Ink4d and Kip1 inhibitors of cyclin-dependent kinases. (4/73)

Development of the central nervous system requires proliferation of neuronal and glial cell precursors followed by their subsequent differentiation in a highly coordinated manner. The timing of neuronal cell cycle exit and differentiation is likely to be regulated in part by inhibitors of cyclin-dependent kinases. Overlapping and sustained patterns of expression of two cyclin-dependent kinases, p19(Ink4d) and p27(Kip1), in postmitotic brain cells suggested that these proteins may be important in actively repressing neuronal proliferation. Animals derived from crosses of Ink4d- null with Kip1-null mice exhibited bradykinesia, proprioceptive abnormalities, and seizures, and died at about 18 days after birth. Metabolic labeling of live animals with bromodeoxyuridine at postnatal days 14 and 18, combined with immunolabeling of neuronal markers, showed that subpopulations of central nervous system neurons were proliferating in all parts of the brain, including normally dormant cells of the hippocampus, cortex, hypothalamus, pons, and brainstem. These cells also expressed phosphorylated histone H3, a marker for late G(2) and M-phase progression, indicating that neurons were dividing after they had migrated to their final positions in the brain. Increased proliferation was balanced by cell death, resulting in no gross changes in the cytoarchitecture of the brains of these mice. Therefore, p19(Ink4d) and p27(Kip1) cooperate to maintain differentiated neurons in a quiescent state that is potentially reversible.  (+info)

INK4d-deficient mice are fertile despite testicular atrophy. (5/73)

The INK4 family of cyclin-dependent kinase (CDK) inhibitors includes four 15- to 19-kDa polypeptides (p16(INK4a), p15(INK4b), p18(INK4c), and p19(INK4d)) that bind to CDK4 and CDK6. By disrupting cyclin D-dependent holoenzymes, INK4 proteins prevent phosphorylation of the retinoblastoma protein and block entry into the DNA-synthetic phase of the cell division cycle. The founding family member, p16(INK4a), is a potent tumor suppressor in humans, whereas involvement, if any, of other INK4 proteins in tumor surveillance is less well documented. INK4c and INK4d are expressed during mouse embryogenesis in stereotypic tissue-specific patterns and are also detected, together with INK4b, in tissues of young mice. INK4a is expressed neither before birth nor at readily appreciable levels in young animals, but its increased expression later in life suggests that it plays some checkpoint function in response to cell stress, genotoxic damage, or aging per se. We used targeted gene disruption to generate mice lacking INK4d. These animals developed into adulthood, had a normal life span, and did not spontaneously develop tumors. Tumors did not arise at increased frequency in animals neonatally exposed to ionizing radiation or the carcinogen dimethylbenzanthrene. Mouse embryo fibroblasts, bone marrow-derived macrophages, and lymphoid T and B cells isolated from these animals proliferated normally and displayed typical lineage-specific differentiation markers. Males exhibited marked testicular atrophy associated with increased apoptosis of germ cells, although they remained fertile. The absence of tumors in INK4d-deficient animals demonstrates that, unlike INK4a, INK4d is not a tumor suppressor but is instead involved in spermatogenesis.  (+info)

Distinct versus redundant properties among members of the INK4 family of cyclin-dependent kinase inhibitors. (6/73)

p16(INK4a), p15(INK4b), p18(INK4c) and p19(INK4d) comprise a family of cyclin-dependent kinase inhibitors and tumor suppressors. We report that the INK4 proteins share the ability to arrest cells in G1, and interact with CDK4 or CDK6 with similar avidity. In contrast, only p18 and particularly p19 are phosphorylated in vivo, and each of the human INK4 proteins shows unique expression patterns dependent on cell and tissue type, and differentiation stage. Thus, the INK4 proteins harbor redundant as well as non-overlapping properties, suggesting distinct regulatory modes, and diverse roles for the individual INK4 family members in cell cycle control, cellular differentiation, and multistep oncogenesis.  (+info)

Stat3-dependent induction of p19INK4D by IL-10 contributes to inhibition of macrophage proliferation. (7/73)

We have previously reported that IL-10 inhibits proliferation of normal bone marrow-derived macrophages and of the monocyte/macrophage cell line J774. Activation of Stat3 was shown to be necessary and sufficient to mediate inhibition of proliferation. To investigate further the mechanism of growth arrest, we examined the effect of IL-10 on expression of cell cycle inhibitors. We found that IL-10 treatment increases expression of the cyclin-dependent kinase inhibitors p19INK4D and p21CIP1 in macrophages. IL-10 cannot induce p19INK4D expression or block proliferation when Stat3 signaling is blocked by a dominant negative Stat3 or a mutant IL-10Ralpha which does not recruit Stat3 in J774 cells, whereas p21CIP1 induction is not affected. An inducibly active Stat3 (coumermycin-dimerizable Stat3-Gyrase B), which suppresses J774 cell proliferation, also induced p19INK4D expression. Sequencing of the murine p19INK4D promoter revealed two candidate Stat3 binding sites, and IL-10 treatment activated a reporter gene controlled by this promoter. These data suggest that Stat3-dependent induction of p19INK4D mediates inhibition of proliferation. Enforced expression of murine p19INK4D cDNA J774 cells significantly reduced their proliferation. Use of antisense p19INK4D and analysis of p19INK4D-deficient macrophages confirmed that p19INK4D is required for optimal inhibition of proliferation by IL-10, and indicated that additional IL-10 signaling events contribute to this response. These data indicate that Stat3-dependent induction of p19INK4D and Stat3-independent induction of p21CIP1 are important components of the mechanism by which IL-10 blocks proliferation in macrophages.  (+info)

Ubiquitin/proteasome-mediated degradation of p19INK4d determines its periodic expression during the cell cycle. (8/73)

Assembly and activity of the proto-oncogenic cyclin D/CDK4(6) complexes, the major driving force of G1 phase progression, is negatively regulated by a family of INK4 CDK inhibitors p16INK4a, p15INK4b, p18INK4c, and p19INK4d. Expression of the INK4 family members is controlled at the transcriptional level, through differential response to environmental and intracellular signals such as cytokines, oncogenic overload, or cellular senescence. Here we show that the periodic oscillation of the p19INK4d protein during the cell cycle is determined by the ubiquitin/proteasome-dependent mechanism, allowing the protein abundance to follow the changes in its mRNA expression. Within the INK4 family, this regulatory mode appears restricted to p19INK4d whose ubiquitination was dependent on the integrity of lysine 62, and binding to CDK4. These results highlight unexpected differences among the INK4 inhibitors, and suggest how p19INK4d may help regulate the rate of cyclin D/CDK4(6) complex formation, and thereby timely progression through the mammalian cell division cycle. Oncogene (2000) 19, 2870 - 2876  (+info)

The other ink recipe threads are dying, and nobody wants to read through 10 pages to find what they want. Therefore I decided to start a new one. This thread is intended for those who dont know much about ink to start learning. Im giving it my best shot to answer all of your questions. Now, lets ...
Investigator of human and animal mysteries since 1960. Swamp Thing character Coleman Wadsworth in #4:7 and more in #4:8, is a tribute. Author of over 35 books, including The Unidentified (1975), Mysterious America (1983/2007), Suicide Clusters (1987), Cryptozoology A to Z (1999), Bigfoot! (2003), The Copycat Effect (2004), and field guides. Educated in anthropology-zoology at SIU-Carbondale, and psychiatric social work at Simmons College School of Social Work. Began doctoral work in anthropology (Brandeis University) and family violence (UNH). Taught at NE universities (1980 to 2003), while concurrently a senior researcher at the Muskie School (1983 to 1996), before retiring to write, lecture, consult, & open museum. Popular documentary course was taught for 23 semesters; appeared on C2C, The Larry King Show, MonsterQuest, Lost Tapes, In Search Of, and other tv programs. Loren Coleman is a dedicated father (Caleb, Malcolm, Des), cryptozoologist, media consultant, and baseball fan ...
Forensic Analysis of Pens & Inks. Video link. http://www.youtube.com/watch?v=I34tz5nIPCs 9 min. Inks appearing on questioned documents may be examined for the purpose of comparing with other inks on the same document, with ink on other documents or even with ink in seized pens....
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was one of the ladies. It waited 5 years now to get finished. Due to the fact that Im teaching a Dear Jane class locally Ill get practice with the border and scalloped edges on this UFO - ...
Page one so far. Ive still got to tidy it up and add a bit more line work. I am enjoying doing this little project. its a good bi ...
Tsvangirai added, If Zimbabwe proceeds to use the BVR system, which Zanu PF is not keen to do, we are also aware of plans to have Nikuv International Projects work with some named Indian companies in hacking or engaging in cyber- attacks on the whole electoral system once it becomes clear that the results are not going in Zanu PFs favour.. We are aware therefore that plans are afoot to either control or derail the BVR process, frustrate voter registration and the actual voting in perceived opposition strongholds. We know as well that there are plans to tamper with silver nitrate and other inks such as UV ink that may be used in order to fudge the result of the next election.. Tsvangirai said the national executive resolved that the MDC-T, together other parties, would utilize all legitimate and constitutionally permissible avenues at our disposal to stop this daylight theft.. Whether in the courts or in the streets, we shall fight all attempts to steal the next election and we fully ...
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An ink stain can make the most professional printed cards look sloppy and undesirable. Using white-out to cover an ink stain or mistake provides a solution, but leaves its own undesirable mark. Fortunately, ink mistakes are much easier to remove from card stock than from thinner paper. Common methods of ink removal include blotting, bleaching and scraping, or a combination of the three.. ...
The type of paper used is not the only reason why ink can be absorbed and dried on a piece of paper; the ink itself also plays a part. There are many different types of ink today
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"Entrez Gene: CDKN2D cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4)". Hirai H, Roussel MF, Kato JY, et al. (1995). " ... 2004). "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27( ... "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. Biol. 15 ... Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene. The protein encoded by this ...
"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, ...
"Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. Biol ... CDK4, CMM3, PSK-J3, cyclin-dependent kinase 4, cyclin dependent kinase 4. ... See also CDK inhibitor for inhibitors of various CDKs. Interactions[edit]. Cyclin-dependent kinase 4 has been shown to interact ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ...
... are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Molecular and Cellular Biology. 15 (5): 2672-81. doi: ... Hirai H, Roussel MF, Kato JY, Ashmun RA, Sherr CJ (May 1995). "Novel INK4 proteins, p19 and p18, ... Cyclins function as regulators of cyclin-dependent kinases. Different cyclins exhibit distinct expression and degradation ... "Cyclin D- and E-dependent kinases and the p57(KIP2) inhibitor: cooperative interactions in vivo". Molecular and Cellular ...
"Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ... CDKN2C, INK4C, p18, p18-INK4C, cyclin-dependent kinase inhibitor 2C, cyclin dependent kinase inhibitor 2C. ... CDKN2C‏ (Cyclin dependent kinase inhibitor 2C) هوَ بروتين يُشَفر بواسطة جين CDKN2C في الإنسان.[1][2][3] ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". مؤرشف من الأصل في 05 ديسمبر 2010.. الوسيط , ...
1995). "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. ... "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. ...
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. ...
Furthermore, inhibitors of the INK4 family members like p15, p16, p18 and p19 inhibit the monomer of CDK6, preventing the ... Cyclin D1, Cyclin D3, P16, PPM1B, and PPP2CA. Cell cycle Cyclin-dependent kinase Cyclin-dependent kinase 4 Mitosis The ... "Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein ...
cyclin-dependent protein kinase inhibitor activity. • protein binding. • transcription factor binding. • protein kinase binding ... CDKN2A; ARF; CDK4I; CDKN2; CMM2; INK4; INK4A; MLM; MTS-1; MTS1; P14; P14ARF; P16; P16-INK4A; P16INK4; P16INK4A; P19; P19ARF; ... negative regulation of cyclin-dependent protein kinase activity. • negative regulation of transcription, DNA-dependent. • ... transcription, DNA-dependent. • rRNA processing. • negative regulation of protein kinase activity. • induction of apoptosis. • ...
CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proceedings of the National ... protein serine/threonine kinase activity. • cyclin-dependent protein serine/threonine kinase activity. ... The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate ...
CDK抑制因子(英语:Cyclin-dependent kinase inhibitor protein). *INK4a/ARF(p14arf/p16、p15、p18、p19) ... Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle. BioEssays. June 1995, 17 (6): 471-80. PMID ... 細胞週期的進行是由不同的週期素(Cyclin)所調控。週期素意味著這些蛋白質的表現量會隨著細胞週期的進行而有所變化,進而確認週期素原來是扮演細胞
The cell cycle is regulated by complex network of cyclins, cyclin-dependent kinases (Cdk), cyclin-dependent kinase inhibitors ( ... Furthermore, regulators of Cdk4 and Cdk6 activity, such as members of the Ink family of inhibitors (p15, p16, p18, and p19), ... hESCs show that the activities of Cyclin E/Cdk2 and Cyclin A/Cdk2 complexes are cell cycle-dependent and the Rb checkpoint in ... However, in mESCs, this typically ordered and oscillatory activity of Cyclin-Cdk complexes is absent. Rather, the Cyclin E/Cdk2 ...
... serum amyloid A-activating factor 1 inhibits cell proliferation by the induction of cyclin-dependent protein kinase inhibitor ... during the neural differentiation of P19 EC cells". Biochem. Biophys. Res. Commun. 286 (5): 1087-1097. doi:10.1006/bbrc. ... are regulated by casein kinase II". Biochem. Biophys. Res. Commun. 262 (1): 198-205. doi:10.1006/bbrc.1999.1130. PMID 10448092 ... during the neural differentiation of P19 EC cells". Biochem. Biophys. Res. Commun. 286 (5): 1087-1097. doi:10.1006/bbrc. ...
It specifically recognizes and promotes the degradation of phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also ... "Chromosomal mapping of the genes for the human CDK2/cyclin A-associated proteins p19 (SKP1A and SKP1B) and p45 (SKP2)". ... 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 ...
... cyclin-dependent kinase inhibitor p18 MeSH D12.776.624.776.355.400 - cyclin-dependent kinase inhibitor p19 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 ...
"Chromosomal mapping of the genes for the human CDK2/cyclin A-associated proteins p19 (SKP1A and SKP1B) and p45 (SKP2)". ... S-phase kinase-associated protein 2, and other regulatory proteins involved in ubiquitin dependent proteolysis. The encoded ... Wu G, Lyapina S, Das I, Li J, Gurney M, Pauley A, Chui I, Deshaies RJ, Kitajewski J (November 2001). "SEL-10 is an inhibitor of ... "p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase". Cell. 82 (6): 915-25. doi:10.1016/0092-8674(95 ...
receptor serine/threonine kinase binding. • peroxisome proliferator activated receptor binding. • ubiquitin binding. ... Inhibitors of the MDM2-p53 interaction include the cis-imidazoline analog nutlin.[10] ... Honda R, Yasuda H (March 2000). "Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger ... Zhao L, Samuels T, Winckler S, Korgaonkar C, Tompkins V, Horne MC, Quelle DE (January 2003). "Cyclin G1 has growth inhibitory ...
... cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase inhibitor 1A. External IDs. OMIM: 116899 MGI: 104556 HomoloGene: ... CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) ... cyclin binding. • cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine ...
All these phases in the cell cycle are highly regulated by cyclins, cyclin-dependent kinases, and other cell cycle proteins. ... CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... Generation of pressure is dependent on formin-mediated F-actin nucleation[71] and Rho kinase (ROCK)-mediated myosin II ... This can occur when cells become overcrowded (density-dependent inhibition) or when they differentiate to carry out specific ...
... *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... cyclin E, A (Cdk2,1) cyclin A, B, B3 (Cdk1) H. sapiens cyclin D 1,2,3 (Cdk4, Cdk6) cyclin E (Cdk2) cyclin A (Cdk2, Cdk1) cyclin ... Cyclin A / CDK2 - active in S phase.. *Cyclin D / CDK4, Cyclin D / CDK6, and Cyclin E / CDK2 - regulates transition from G1 to ...
CDK-activating kinase. CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19) ... Caspases are proteins that are highly conserved, cysteine-dependent aspartate-specific proteases. There are two types of ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... Using these inhibitors it was discovered that cells can die ... The characterization of the caspases allowed the development of caspase inhibitors, which can be used to determine whether a ...
CDK-activating kinase. CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19) ... April 2010). "Apoptosis induced by Oropouche virus infection in HeLa cells is dependent on virus protein expression". Virus Res ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... Using these inhibitors it was discovered that cells can die ... The characterization of the caspases allowed the development of caspase inhibitors, which can be used to determine whether a ...
CDK-activating kinase. CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19) ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... cAMP-dependent pathway. *Ca2+ signaling. *Lipid signaling. ... "Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic ...
CDK-activating kinase. CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19) ... GTP-dependent protein binding. • GTPase activity. • mitogen-activated protein kinase kinase kinase binding. • protein binding. ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... "The MAP kinase kinase kinase MLK2 co-localizes with activated ... protein kinase binding. • nucleotide binding. • GTP binding. • identical protein binding. Cellular component. • cytoplasm. • ...
... is a specific inhibitor of cyclin-dependent kinases CDK4 and CDK6. CDK4 is a subunit of the protein kinase complex that is ... p19; CDK inhibitor p19INK4d; inhibitor of cyclin-dependent kinase 4d; cyclin-dependent kinase 4 inhibitor D p19; cell cycle ... cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4). Background. Cyclin-dependent kinase 4 inhibitor D (CDKN2D) is a ... CDKN2D; cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4); cyclin-dependent kinase 4 inhibitor D; INK4D; ...
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. ...
"Entrez Gene: CDKN2D cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4)". Hirai H, Roussel MF, Kato JY, et al. (1995). " ... 2004). "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27( ... "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. Biol. 15 ... Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene. The protein encoded by this ...
"Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. Biol ... CDK4, CMM3, PSK-J3, cyclin-dependent kinase 4, cyclin dependent kinase 4. ... See also CDK inhibitor for inhibitors of various CDKs. Interactions[edit]. Cyclin-dependent kinase 4 has been shown to interact ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ...
Cyclin Dependent Kinase Inhibitor 2D, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards ... cyclin dependent kinase 4 and 6 (CDK4/CDK6) inhibitor,p19,regulator of the cell cycle,passage through the G1 checkpoint, ... annotations related to this gene include protein kinase binding and cyclin-dependent protein serine/threonine kinase inhibitor ... Cyclin-dependent kinase 4 inhibitor D. Protein Accession:. P55273. Secondary Accessions: *Q13102 ...
Cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4). NM_001800. NM_079421. Gene Info. ... Cyclin-dependent kinase inhibitor 1B (p27, Kip1). NM_004064. Gene Info. CDKN2A. Cyclin-dependent kinase inhibitor 2A. NM_ ... Cyclin-dependent kinase inhibitor 1A (p21, Cip1). NM_001220778. NM_000389. NM_078467. NM_001220777. Gene Info. ... Cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4). NM_001262. NM_078626. Gene Info. ...
cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4). Protein Similarities Based on Shared Motif Content. ... MF] cyclin-dependent protein kinase inhibitor activity *[MF] protein kinase binding BioCarta Pathways. ... BP] regulation of cyclin-dependent protein kinase activity *[BP] response to UV *[BP] response to retinoic acid *[BP] response ... CDKN2D, cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4). Sequence ID:. NM_001800. NM_079421. ...
Cyclin-dependent protein kinases and their inhibitors, such as p19INK4d, regulate the different stages of the cell cycle. Here ... Cell cycle progression is tightly regulated by cyclin-dependent kinases (CDKs). The ankyrin-repeat protein p19INK4d functions ... which dissociates its cyclin-dependent protein kinase-inhibitory complex and primes p19INK4d for cellular degradation. Our ... dependent protein kinases (CDK1), respectively, leads to local unfolding of the three N-terminal ankyrin repeats of p19INK4d. ...
Cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4). Aliases:. INK4d, p19, p19INK4d. ...
Knockdown of cyclin-dependent kinase inhibitor p19INK4d impairs human terminal erythroid differentiation by decreasing GATA1 ... cyclin-dependent kinases and cyclin-dependent kinase inhibitors (CDKI), yet their roles in erythropoiesis remain to be fully ... Further biochemical analysis revealed that p19INK4d directly binds to Raf kinase inhibitor PEBP1 and that p19INK4d knockdown ... As GATA1 protein is protected by nuclear HSP70, we examined the effects of p19INK4d knockdown on HSP70 and found that p19INK4d ...
... lacking the cyclin-dependent kinase inhibitors p16INK4a and p19ARF. Our results demonstrate that blockage of K+ channels and ... cyclins and cyclin-dependent kinase inhibitors (cdkis) known to regulate cell cycle progression through this phase are affected ... 1997) Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of oligodendrocyte differentiation. EMBO J ... Blockage of K+ channels and membrane depolarization also caused accumulation of the cyclin-dependent kinase inhibitors p27Kip1 ...
... senescence and differentiation via specific protein-protein interactions with the cyclins, cyclin-dependent kinase (Cdk), and ... thereby establishing a role for NFI in the cell cycle dependent expression of p21. ... The cyclin-dependent kinase inhibitor 1A (CDKN1A), also known as p21 (WAF1/CIP1) modulates cell cycle, apoptosis, ... promoter provides evidence for complex combinatorial regulation in undifferentiated and differentiated P19 cells.. *Raphaël ...
Absence of p19INK4d Leads to a Progressive Age-Dependent Increase in the Number of MKs in BM and Spleen of Mice(A and B) Number ... Cyclin-Dependent Kinase Inhibitor p19/deficiency/genetics*/metabolism. *DNA Damage*. *Hematopoietic Stem Cells/cytology*/ ... fig5: Absence of p19INK4d Leads to a Progressive Age-Dependent Increase in the Number of MKs in BM and Spleen of Mice(A and B) ... fig5: Absence of p19INK4d Leads to a Progressive Age-Dependent Increase in the Number of MKs in BM and Spleen of Mice(A and B) ...
Identification of calpain cleavage sites in the G1 cyclin-dependent kinase inhibitor p19(INK4d). In: Biological Chemistry, Vol ... Jochum, Marianne und Bittner, A. (1983): Inter-alpha-Trypsin Inhibitor of Human Serum. An Inhibitor of Polymorphonuclear ... Fritz, Hans; Collins, John und Jochum, Marianne (1992): Proteinase inhibitor candidates for therapy of enzyme-inhibitor ... Effects of proteinase inhibitors and of leukocyte depletion. In: Blood, Vol. 79, Nr. 11: S. 3071-3075 [PDF, 1MB] ...
Structure of the Cyclin-Dependent Kinase Inhibitor P19(Ink4D). Yuh FY, Archer SJ, Domaille PJ, Smith BO, Owen D, Brotherton DH ... Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d). Brotherton ...
Gene expression of cyclin dependent kinase inhibitor p21^,WAF1, was not increased by G-CSF stimulation, while levels of mRNA ... Therefore, expression of p27^,KIP1, and p19^,INK4D, appeared to prevent the cell-cycle progression from G1 to S during G-CSF ... Its also possible that C/EBPα and/or C/EBPε transcription factors control the gene expression … More of these CDK inhibitors. ... G-CSF dependent expression of ERO1-L gene appeared to be in control of Stat3 activation during neutrophil differentiation. ...
Review of alterations of cyclin-dependent kinase inhibitor INK4 family genes p15, p16, p18 and p19 in human leukemia-lymphoma ... p15, a target of transforming growth factor-β signaling,16 is an inhibitor of the cyclin-dependent kinase-417 18 and a negative ... Inactivation of the cyclin-dependent kinase inhibitor p15INK4b by deletion and de novo methylation with independence of ... p16 and p15, 2 inhibitors of cyclin-dependent kinases, are frequently hypermethylated in hematologic neoplasias. Decitabine, or ...
C) Transcript levels of cyclin-dependent kinase inhibitors in Ezh2 mutant (Ezh2fl/fl:Cγ1-cre) iGB cells relative to control ( ... Expression of p19ARF encoded by Cdkn2a was also assessed. Columns represent mean ± SEM. (D) Summary data on cell cycle ... EZH2 was also critical to prevent the expression of the cyclin-dependent kinase inhibitor p16INK4A encoded by the Cdkn2a locus ... T cell-dependent antibody responses and memory B cells depend on EZH2 catalytic function in GC B cells. (A) NP-specific IgG1 ...
1997) Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell 91:649-659. ... 1996) Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27Kip1. Cell 85:721-732. ... Two families of cyclin-dependent kinase (CDK) inhibitors, totaling seven genes, have been identified in mammalian cells. Their ... 1999) The p21Cip1 and p27Kip1 CDK inhibitors are essential activators of cyclin D-dependent kinases in murine fibroblasts. ...
Showing subcellular location of CDKN2A (ARF, CDK4I, CDKN2, CMM2, INK4, INK4a, MLM, MTS1, p14, p14ARF, p16, p16INK4a, p19, ... Cyclin-dependent kinase inhibitor 2A K7PML8 [Target identity:100%; Query identity:100%]. Cyclin-dependent kinase inhibitor 2A ... ARF, CDK4I, CDKN2, CMM2, INK4, INK4a, MLM, MTS1, p14, p14ARF, p16, p16INK4a, p19, p19Arf. ... Cyclin dependent kinase inhibitor 2A. Protein classi. Protein class the gene product belongs to according to selected gene ...
Molecular analysis of the cyclin-dependent kinase inhibitor genes, p15, p16, p18 and p19 in the myelodysplastic syndromes. Leuk ... a mechanism requiring protein kinase C, calmodulin-dependent kinase II, ERK, and c-Src. J Biol Chem 280:34617-34625PubMed ... Roboz GJ, Giles FJ, List AF et al (2006) Phase 1 study of PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor ... Muller-Tidow C, Wang W, Idos GE et al (2001) Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at ...
1995) Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases Cdk4 and Cdk6. Mol. Cell. ... 1996) Cyclin-dependent kinase-2 (Cdk2) forms an inactive complex with cyclin D1 since Cdk2 associated with cyclin D1 is not ... Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in ... 1994) The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 369:574-578. ...
For example, induction of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1 leads to G1 cell cycle arrest. The increased ... p14ARF and p19 ARF, respectively) were found to interact with Mdm2 and to block Mdm2-mediated p53 degradation (Kamijo et al., ... ARF is a small basic protein (pI,12) encoded by the INK4a locus that also encodes the cyclin-dependent kinase inhibitor ... Low doses of the RNA synthesis inhibitor actinomycin D and nuclear export inhibitor leptomycin B can induce the accumulation of ...
Inhibition of Ribosome Biogenesis by p19(ARF). CDKN2A (Cyclin Dependent Kinase Inhibitor-2A), which is also referred to as p16( ... Cyclin Dependent Kinase Inhibitor-2A) belongs to the CDKN family which show specificity for G1 phase CDKs (Cyclin-Dependent ... Cyclin-dependent kinases) are a group of serine/threonine protein kinases activated by binding to a regulatory subunit cyclin. ... dependent Protein Kinase, commonly known as PKA (Protein Kinase-A), is a second messenger-dependent enzyme that has been ...
... and the cyclin-dependent kinase inhibitors p21 (also known as WAF1 and CDKN1A) (Bloom et al., 2003; Coulombe et al., 2004), p19 ... 1995). Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappa B inhibitor for degradation via the ubiquitin- ... the extracellular signal-regulated kinase 3 (ERK3) and cyclin G1 (Li et al., 2009). Similarly, the peroxisome proliferator- ... a ubiquitin-dependent mechanism and a ubiquitin-independent but PA28gamma-dependent mechanism. J. Virol. 83, 2389-2392. ...
... which induces the cyclin-dependent kinase inhibitor p21Cip1 in a p53-dependent manner (14). A retrovirus encoding p19ARF ... and it depends upon functional p53 to transcriptionally induce mdm2 and the cyclin-dependent kinase inhibitor p21Cip1, and to ... a protein that specifically inhibits the ability of cyclin D-dependent kinases (1) to phosphorylate retinoblastoma protein (8- ... Under these conditions, levels of p19ARF that were insufficient to fully activate p53-dependent gene expression restored the ...
The cyclin-dependent kinase inhibitors p19(Ink4d) and p27(Kip1) are coexpressed in select retinal cells and act cooperatively ... including the cyclins, cyclin dependent kinases (Cdks), Cdk inhibitors such as the Kip/Cip and Ink families, tumor suppressors ... Role of cyclin D1 and cyclin-dependent kinase inhibitors. Dev. Biol. 2010, 337, 134-146. [Google Scholar] ... The differentiated state is further maintained by high levels of cyclin dependent kinase inhibitors (CDKIs) and retinoblastoma ...
"Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ... CDKN2C, INK4C, p18, p18-INK4C, cyclin-dependent kinase inhibitor 2C, cyclin dependent kinase inhibitor 2C. ... CDKN2C‏ (Cyclin dependent kinase inhibitor 2C) هوَ بروتين يُشَفر بواسطة جين CDKN2C في الإنسان.[1][2][3] ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". مؤرشف من الأصل في 05 ديسمبر 2010.. الوسيط , ...
Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc ... The related BCL-W/BCL-XL inhibitor venetoclax also clears irradiation-induced lung SNCs and skin SNCs produced by p19Arf ... For example, Ras stabilizes p53 to upregulate the cyclin-dependent kinase 2 (CDK2) inhibitor p21Cip/Waf, thereby blocking Rb ... Enhanced susceptibility of cyclin kinase inhibitor p21 knockout mice to high fat diet induced atherosclerosis. J Biomed Sci. ...
... cyclin-dependent kinase inhibitor 2A,cyclin-dependent kinase inhibitor p16,multiple tumor suppressor 1 ... ARF,CDK4I,CDKN2,CMM2,INK4,INK4a,MLM,MTS1,TP16,p14,p14ARF,p16,p16INK4,p16INK4a,p19 ... two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript ... In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, ...
  • Cyclin-dependent protein kinases and their inhibitors, such as p19 INK4d , regulate the different stages of the cell cycle. (pnas.org)
  • Here, we demonstrate how sequential phosphorylation of p19 INK4d at two sites first destabilizes and then unfolds the N-terminal half of the protein, which dissociates its cyclin-dependent protein kinase-inhibitory complex and primes p19 INK4d for cellular degradation. (pnas.org)
  • Here, we combine cell and structural biology methods to unravel the mechanism by which p19 INK4d controls cell cycle progression. (pnas.org)
  • We delineate how the stepwise phosphorylation of p19 INK4d Ser66 and Ser76 by cell cycle-independent (p38) and -dependent protein kinases (CDK1), respectively, leads to local unfolding of the three N-terminal ankyrin repeats of p19 INK4d . (pnas.org)
  • This dissociates the CDK6-p19 INK4d inhibitory complex and, thereby, activates CDK6. (pnas.org)
  • CDK6 triggers entry into S-phase, whereas p19 INK4d is ubiquitinated and degraded. (pnas.org)
  • Our findings reveal how signaling-dependent p19 INK4d unfolding contributes to the irreversibility of G1/S transition. (pnas.org)
  • Knockdown of cyclin-dependent kinase inhibitor p19 INK4d impairs human terminal erythroid differentiation by decreasing GATA1 protein levels. (bloodjournal.org)
  • GATA1 protein level is regulated by p19 INK4d via PEBP1-pERK-HSP70-GATA1 pathway. (bloodjournal.org)
  • We show here that p19 INK4d , a member of CDKI family, is abundantly expressed in erythroblasts and that p19 INK4d knockdown delayed erythroid differentiation, inhibited cell growth, led to increased apoptosis and generation of abnormally nucleated late stage erythroblasts. (bloodjournal.org)
  • Unexpectedly, p19 INK4d knockdown did not affect cell cycle. (bloodjournal.org)
  • As GATA1 protein is protected by nuclear HSP70, we examined the effects of p19 INK4d knockdown on HSP70 and found that p19 INK4d knockdown led to decreased expression of HSP70 and its nuclear localization. (bloodjournal.org)
  • Further biochemical analysis revealed that p19 INK4d directly binds to Raf kinase inhibitor PEBP1 and that p19 INK4d knockdown increased the expression of PEBP1 that in turn led to reduced ERK activation. (bloodjournal.org)
  • Thus we have identified an unexpected role for p19 INK4d via a novel PEBP1-pERK-HSP70-GATA1 pathway. (bloodjournal.org)
  • p19 INK4d controls hematopoietic stem cells in a cell-autonomous manner during genotoxic stress and through the microenvironment during aging. (nih.gov)
  • We demonstrate that p19(INK4d) is involved in the regulation of HSC quiescence by inhibition of the G0/G1 cell cycle transition.Deletion of p19(INK4d) results in megakaryocyte hyperproliferation and increased transforming growth factor β1 secretion.This leads to fibrosis in the bone marrow and spleen, followed by loss of HSCs during aging. (nih.gov)
  • P19 INK4d antibody LS-C323724 is an unconjugated rabbit polyclonal antibody to p19 INK4d (CDKN2D) from human and mouse. (lsbio.com)
  • CDKN2D / p19 INK4d is a member of the INK4 family of cyclin-dependent kinase inhibitors. (lsbio.com)
  • showed that inhibition of Notch pathway activity signature results in the upregulation of cyclin-dependent kinase inhibitors CDKN2D (p19 INK4d) and CDKN1b (p27 Kip1) and the subsequent derepression of Rb. (aacrjournals.org)
  • CDK activity is regulated by 2 families of inhibitors: INK4 proteins, including INK4A (p16), INK4B (p15), INK4C (p18), and INK4D (p19), and the Cip and Kip family, which is composed of p21 (Cipl), p27 (Kipl), and p57 (Kip2) (5), (8). (thefreedictionary.com)
  • However, the roles of p19 INK4d in terminal erythropoiesis are still unknown. (biomedcentral.com)
  • As reported in our article recently published in Blood entitled "Unexpected roles for p19 INK4d in posttranscriptional regulation of GATA1 and modulation of human terminal erythropoiesis" [ 3 ], we demonstrated what roles p19 INK4d plays in human terminal erythropoiesis. (biomedcentral.com)
  • We found that, in the erythropoietin-induced, CD34-positive hematopoietic stem cell (HSC) differentiation system, knockdown of p19 INK4d delays terminal erythroid differentiation, inhibits erythroblast growth due to increased apoptosis, and leads to the generation of abnormally nucleated late-stage erythroblasts. (biomedcentral.com)
  • Unexpectedly, knockdown of p19 INK4d did not affect cell cycle, and these functions caused by p19 INK4d knockdown were via decreasing levels of GATA-binding protein 1 (GATA1). (biomedcentral.com)
  • Furthermore, we found that p19 INK4d modulates GATA1 protein levels through a novel pathway, the phosphatidylethanolamine-binding protein 1 (PEBP1)-phosphorylated extracellular signal-regulated kinase ( p ERK)-heat shock 70 kDa protein (HSP70)-GATA1 pathway [ 3 ]. (biomedcentral.com)
  • However, as shown in our study, p19 INK4d played important roles independent of cell cycle regulation, and the lack of cell cycle change was probably due to the compensatory up-regulation of p18 INK4c following p19 INK4d knockdown. (biomedcentral.com)
  • In conclusion, our study revealed the cell cycle-independent roles of p19 INK4d in human terminal erythropoiesis via a novel PEBP1- p ERK-HSP70-GATA1 pathway. (biomedcentral.com)
  • Polypyrimidine tract-binding protein induces p19(ink4d) expression and inhibits the proliferation of h1299 cells. (biomedcentral.com)
  • Mouse anti Human p19 antibody, clone DCS100.1 recognizes human p19-INK4d, also known as Cyclin-dependent kinase 4 inhibitor D. p19-INK4d is a 166 amino acis ~19 kDa tumor suppressor protein, a specific inhibitor of cdk4/cdk6. (bio-rad-antibodies.com)
  • p16 Ink4a , p15 Ink4b , p18 Ink4c and p19 Ink4d , and they bind specifically to Cdk4 and Cdk6, thereby negatively regulating their kinase activities and cell cycle progression. (diva-portal.org)
  • The overall aim of this thesis was to study the roles of p18 Ink4c and p19 Ink4d using in vivo models of cancer and embryonic development. (diva-portal.org)
  • The distinct role of THPO in postnatal HSC maintenance is accompanied by accelerated HSC cell-cycle kinetics in Thpo(-/-) mice and reduced expression of the cyclin-dependent kinase inhibitors p57(Kip2) and p19(INK4D) as well as multiple Hox transcription factors. (ox.ac.uk)
  • It is also called MTS1 and INK4a, and p15 INK4b (MTS2), p18 INK4c and p19 INK4d are other members of the INK4 family. (takarabio.com)
  • Cyclin-dependent kinase 4 inhibitor D (CDKN2D) is a specific inhibitor of cyclin-dependent kinases CDK4 and CDK6. (creativebiomart.net)
  • This protein has been shown to form a stable complex with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus function as a cell growth regulator that controls cell cycle G1 progression. (wikipedia.org)
  • Ribociclib are US FDA approved CDK4 and CDK6 inhibitors for the treatment of estrogen receptor positive/ HER2 negative advanced breast cancer. (wikipedia.org)
  • Furthermore, the senescent-cell-cycle arrest occurs prior to the accumulation of the Cdk4-Cdk6 inhibitor p16 Ink4a , suggesting that p21 may be sufficient for this event. (asm.org)
  • Instead, the cyclin D1-Cdk4 and cyclin D1-Cdk6 complexes in these cells are associated with an increased amount of p21, suggesting that p21 may be responsible for inactivation of both cyclin E- and cyclin D1-associated kinase activity at the early stage of senescence. (asm.org)
  • Phosphorylation of pRb during G 1 phase is carried out by cyclin D-Cdk4 and cyclin D-Cdk6 (cyclin D-Cdk4/6) and cyclin E-Cdk2 complexes ( 44 , 50 , 55 ). (asm.org)
  • CDKs, as catalytic subunits, become active only in association with their regulatory partner cyclins (e.g., cyclin D-CDK4/CDK6, cyclin E-CDK2, cyclin A-CDK2, cyclin B-CDK1, cyclin C-CDK3). (springer.com)
  • NSCLCs frequently overexpress cyclin D1 (4 , 5 , 6 , 7) , leading to increased activity of cdk4 and cdk6 and loss of growth control. (aacrjournals.org)
  • A gene on chromosome 9p21 that encodes a member of the INK4 family of cyclin-dependent kinase inhibitors, which form a complex with CDK4 or CDK6, preventing activation of CDK kinases and thus acting as cell growth regulators by controlling cell cycle progression through G1. (thefreedictionary.com)
  • The p16 family (p15, p16, p18 and p19) binds to and inhibits the activities of CDK4 and CDK6. (biomedcentral.com)
  • Mouse anti Human p19 antibody, clone DCS100.1 co-precipitates cdk4/cdk6 in immunoprecipitation studies. (bio-rad-antibodies.com)
  • This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6 , whose activity is required for cell cycle G1 / S transition. (wikidoc.org)
  • p16 INK4a is a cyclin-dependent kinase (CDK) inhibitor, and binds CDK4 and CDK6 and inhibits their kinase activity. (takarabio.com)
  • See also CDK inhibitor for inhibitors of various CDKs. (wikipedia.org)
  • Cell cycle progression is tightly regulated by cyclin-dependent kinases (CDKs). (pnas.org)
  • Recent results from investigations of senescent cells suggest that they express G1 cyclins, CDKs, and their inhibitors as well as a typical expression signature of cytokines and their receptors [ 14 - 17 ]. (hindawi.com)
  • Indeed, the only nuclear G1/S molecules are the cell cycle inhibitors, pRb, p57, and variably, p21: none of the cyclins or cdks necessary to drive human β-cell proliferation are present in the nuclear compartment. (diabetesjournals.org)
  • This process is tightly controlled by serine-threonine kinases named cyclin-dependent kinases (CDKs). (springer.com)
  • Full activation of the cyclin-CDK holoenzymes requires phosphorylation at particular sites in CDKs. (springer.com)
  • CDK activity is also negatively regulated by direct interaction with CDK inhibitors, which consist of two families, the inhibitor of CDK4 (INK4) family, which specifically inhibit cyclin D-associated kinases, and the kinase inhibitor protein (Cip/Kip) family, which inhibit most CDKs. (springer.com)
  • CDK inhibitors, cyclins, and CDKs themselves) is a common mechanism responsible for out-of-control cell growth, the main characteristic in cancer. (springer.com)
  • Thus, CDKs are attractive targets for both cancer therapy and neuroprotection, and numerous pharmacological CDK inhibitors have been reported. (springer.com)
  • Cyclin-dependent kinases (Cdks) comprise a promising set of such targets. (aacrjournals.org)
  • Cdks are activated in part by their association with cyclins. (aacrjournals.org)
  • Cyclin-dependent kinases (CDKs) have been considered promising drug targets for a number of years, but most CDK inhibitors have failed rigorous clinical testing. (aspetjournals.org)
  • Cancer is a disease of uncontrolled proliferation, and since CDKs are a central component of the cell cycle engine, great effort has been expended in developing CDK inhibitors as anticancer agents. (aspetjournals.org)
  • Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). (biomedcentral.com)
  • CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs). (biomedcentral.com)
  • The progression of cells through the cell cycle is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs). (biomedcentral.com)
  • Cyclins function as the positive regulators of CDKs. (biomedcentral.com)
  • Cyclins and CDKs assemble into complexes with one another as cells progress through G1 phase, cyclins being required to activate the serine-threonine kinase activity of their catalytic partners. (biomedcentral.com)
  • Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (biomedcentral.com)
  • Progression through the G1, S, G2 and M phases of the cell cycle is controlled by cyclin-dependent kinases (Cdks) and cyclins. (diva-portal.org)
  • Progression through the different phases of the cell cycle is dependent on the activities of cyclin dependent kinases (cdks) bound to their cognate cyclins [ 1 , 2 ]. (biomedcentral.com)
  • Note, this protein should not be confused with p19-ARF (mouse) or the human equivalent p14ARF, which are alternative products of the CDKN2A gene. (wikipedia.org)
  • Previous studies of cell cycle regulating proteins in MLS/RCLS revealed a prominent expression of growth promoting G1 cyclins and cyclin dependent kinases (CDK), coexpressed with cyclin dependent kinase inhibitors P16, P19, and P27 (also known as CDKN2A, CDKN2D, and CDKN1B, resp. (hindawi.com)
  • The human cyclin-dependent kinase inhibitor 2A (CDKN2A) gene generates several transcript variants that differ in their first exons. (clontech.com)
  • CDKN2A (cyclin dependent kinase 2a / p16) Hybridization with Vysis CDKN2A/CEP 9 FISH Probe (Abbott Molecular, US) showing the CDKN2A gene on 9p21.3 (red signals) - Courtesy Adriana Zamecnikova. (atlasgeneticsoncology.org)
  • Seven cyclin-dependent kinase inhibitor proteins have thus far been identified. (wikipedia.org)
  • Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. (wikipedia.org)
  • PKC (Protein Kinase-C) is a cyclic nucleotide-independent enzyme that phosphorylates serine and threonine residues in many target proteins. (qiagen.com)
  • It is a highly specific process that is time- (e.g. cell cycle), compartment- (e.g. nucleus or endoplasmic reticulum) and substrate quality- (e.g. denatured or misfolded proteins) dependent, and allows fast adaptation to changing conditions. (biologists.org)
  • The INK4a-ARF locus encodes two proteins, p16 INK4a and p19 ARF , that restrain cell growth by affecting the functions of the retinoblastoma protein and p53, respectively. (pnas.org)
  • The INK4a-ARF locus encodes two unrelated tumor suppressor proteins, p16 INK4a ( 1 ) and p19 ARF ( 2 ) that act to modify the activities of the retinoblastoma protein and p53, respectively. (pnas.org)
  • While neither p16 INK4a nor p19 ARF are detectably expressed during mouse embryogenesis, explantation of mouse embryo fibroblasts (MEFs) into culture induces the synthesis of both proteins ( 14 , 15 ). (pnas.org)
  • At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. (abnova.com)
  • Previous analysis of cell cycle regulatory proteins revealed a prominent expression of G1-cyclins, cyclin dependent kinases, and their inhibitors but very few cells progressing through the G1/S boundary. (hindawi.com)
  • The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. (nih.gov)
  • Akiyama T, Yoshida T, Tsujita T, Shimizu M, Mizukami T, Okabe M, Akinaga S (1997) G1 phase accumulation induced by UCN-01 is associated with dephosphorylation of Rb and CDK2 proteins as well as induction of CDK inhibitor p21/Cip1/WAF1/Sdi1 in p53-mutated human epidermoid carcinoma A431 cells. (springer.com)
  • Protein expression levels of cell cycle regulating proteins CDK1, CDK2, CDK4, cyclin D1, cyclin E, p19 and p27 were markedly altered by simvastatin. (biomedsearch.com)
  • In addition, two groups of inhibitors, known as Cip/Kip and INK4 proteins, also regulate cdk activity. (aacrjournals.org)
  • Although initially identified as a cell cycle inhibitor based on its homology to other Cip/Kip family proteins, multiple novel functions have been ascribed to p57 Kip2 in recent years that participate in the control of various cellular processes, including apoptosis, migration and transcription. (frontiersin.org)
  • These proteins form active Cdk:cyclin complexes that phosphorylate specific substrates. (diva-portal.org)
  • Here, we show that both early-passage Foxm1(-)(/)(-) mouse embryonic fibroblasts (MEFs) and human osteosarcoma U2OS cells depleted of FoxM1 protein by small interfering RNA fail to grow in culture due to a mitotic block and accumulate nuclear levels of cyclin-dependent kinase inhibitor (CDKI) proteins p21(Cip1) and p27(Kip1). (jax.org)
  • Moreover, early-passage Foxm1(-)(/)(-) MEFs display premature senescence as evidenced by high expression of the senescence-associated beta-galactosidase, p19(ARF), and p16(INK4A) proteins. (jax.org)
  • Absence of p19INK4d Leads to a Progressive Age-Dependent Increase in the Number of MKs in BM and Spleen of Mice(A and B) Number of MK-Ps derived from total BM cells (A) and total spleen cells (B) of 8- to 10-week-old (n = 3) and 20- to 25-week-old (n = 4) mice cultured in fibrin clots. (nih.gov)
  • The p19ink4d cyclin dependent kinase inhibitor gene is altered in osteosarcoma. (biomedcentral.com)
  • The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. (wikipedia.org)
  • INK4 inhibitors (p16 INK4a and the related p19 INK4a ) also distort the Cdk4/6 kinase catalytic cleft and interfere with its ATP binding. (celldeath.de)
  • A putative DNA replication origin has been identified in close proximity of INK4/Arf locus that appears to transcriptionally repress p16 in a manner dependent on CDC6 . (atlasgeneticsoncology.org)
  • This process is in part regulated by a family of Cdk inhibitors (CKIs) called the Ink4 family (Inhibitors of Cdk4). (diva-portal.org)
  • A cyclin-dependent kinase inhibitor protein is a protein which inhibits the enzyme cyclin-dependent kinase (CDK). (wikipedia.org)
  • Exon 1α, 2, and 3 encode p16 INK4a , a protein that specifically inhibits the ability of cyclin D-dependent kinases ( 1 ) to phosphorylate retinoblastoma protein ( 8 - 10 ). (pnas.org)
  • One of these, cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) or p16 INK4a , interacts with, and sequesters, the E3 ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. (clontech.com)
  • p16 INK4a p16 INK4a is a tumor-suppressor which inhibits the cyclin-dependent kinases 4 and 6. (celldeath.de)
  • p21 WAF1/CIP1 p21 WAF1/CIP1 encodes a 21 kDa protein that inhibits the kinase activity of the cdk2-cyclin complex required for transition from G1 to S phase in the cell cycle. (celldeath.de)
  • P16-INK4a interacts strongly with cyclin-dependent kinase 4 and cyclin-dependent kinase 6 and inhibits their ability to interact with cyclins D. P16-INK4a induces cell cycle arrest at G1 and G2/M checkpoints, blocking them from phosphorylating RB1 and preventing exit from G1 phase of the cell cycle. (atlasgeneticsoncology.org)
  • Blockage of K + channels and membrane depolarization also caused accumulation of the cyclin-dependent kinase inhibitors p27 Kip1 and p21 CIP1 in OP cells. (jneurosci.org)
  • The cyclin-dependent kinase inhibitor 1A (CDKN1A), also known as p21 (WAF1/CIP1) modulates cell cycle, apoptosis, senescence and differentiation via specific protein-protein interactions with the cyclins, cyclin-dependent kinase (Cdk), and many others. (semanticscholar.org)
  • UV radiation is a transcriptional inducer of p21(Cip1/Waf1) cyclin-kinase inhibitor in a p53-independent manner. (semanticscholar.org)
  • We show that the Cdk inhibitor p21 Sdi1,Cip1,Waf1 , which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active. (asm.org)
  • The finding that senescent HDF contain elevated amounts of the ubiquitously acting cyclin-dependent kinase inhibitor (CKI) p21 Sdi1,Cip1,Waf1 (p21) ( 40 ) suggested instead that cyclin E-Cdk2 complexes in senescent cells might be inactivated by increased binding of p21. (asm.org)
  • ARF can bind p53-DNA complexes, and it depends upon functional p53 to transcriptionally induce mdm2 and the cyclin-dependent kinase inhibitor p21 Cip1 , and to arrest cell proliferation. (pnas.org)
  • In this setting, reintroduction of p19 ARF restores p53's ability to induce p21 Cip1 and mdm2, implying that, in addition to stabilizing p53, ARF modulates p53-dependent function through an additional mechanism. (pnas.org)
  • Despite the opposite effects on lineage progression, both isoproterenol and the glutamate receptor agonist kainate caused accumulation of the cyclin-dependent kinase inhibitors p27(Kip1)and p21(CIP1), and G1 arrest. (biologists.org)
  • Expression of p21 Waf1/Cip1 , transcriptionally regulated by a p53-dependent pathway (10) , is often decreased in tumors such as NSCLC that harbor p53 mutations. (aacrjournals.org)
  • p21 was simultaneously identified as WAF1 (Wild-type p53-Activated Fragment1) and as CIP1 (Cyclin-dependent kinase Inhibitor Protein), suggesting a direct link between p53 , negative regulation of the kinases required for G1-S transition and therefore G1 arrest. (celldeath.de)
  • The cyclin/CDK inhibitor p57 Kip2 belongs to the Cip/Kip family, with p21 Cip1 and p27 Kip1 , and is the least studied member of the family. (frontiersin.org)
  • However, ARF -null cells exhibit an intact p53-dependent G 1 checkpoint in response to DNA damage by ionizing radiation ( 14 ), so ARF must lie on a different signaling pathway. (pnas.org)
  • PTEN is a phosphatase that negatively regulates the phosphoinositide 3-kinase signaling pathway, including the downstream effector AKT. (aacrjournals.org)
  • While p27 Kip1 is a CDK inhibitor, p130 acts to enforce cell-cycle exit through repression of gene expression as part of the DREAM complex. (aacrjournals.org)
  • It specifically recognizes phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also referred to as p27 or KIP1) predominantly in S phase and interacts with S-phase kinase-associated protein 1 (SKP1 or p19). (nih.gov)
  • mRNA and protein expression patterns in these mice and in cyclin D1-null mice suggest that Chx10 influences p27 Kip1 at a post-transcriptional level, through a mechanism that is largely dependent on cyclin D1. (biologists.org)
  • However, PTEN induced a specific reduction of cyclin D3 levels and an associated increase in the amount of the inhibitor p27 KIP1 complexed with CDK2. (aacrjournals.org)
  • Although PTEN signaling directly regulates p27 KIP1 levels in some settings, in endometrial carcinoma cells, PTEN expression indirectly regulated p27 KIP1 activity by modulating levels of cyclin D3. (aacrjournals.org)
  • Pfn1 overexpression results in increased protein stability of p27 kip1 (p27 - a major cyclin-dependent kinase inhibitor) and marked elevation in the overall cellular level of p27. (pubmedcentralcanada.ca)
  • cdkn2d has several biochemical functions, for example, cyclin-dependent protein serine/threonine kinase inhibitor activity, protein binding, protein kinase binding. (creativebiomart.net)
  • Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene. (wikipedia.org)
  • CDKN2D (Cyclin Dependent Kinase Inhibitor 2D) is a Protein Coding gene. (genecards.org)
  • Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (wikipedia.org)
  • Collectively, these results suggest that simvastatin induces apoptosis in tumor cells and its anti-proliferative activity was accompanied by inhibition of cyclin-dependent kinases and cyclins, whereas CDK inhibitors p19 and p27 were enhanced. (biomedsearch.com)
  • Canonical BMP9 signaling via activin-like kinase-1-Smad1/5/9 was disrupted by inhibition of Notch signaling, even in the absence of exogenous DLL4. (ahajournals.org)
  • Inhibition of notch signaling by gamma secretase inhibitor engages the rb pathway and elicits cell cycle exit in t-cell acute lymphoblastic leukemia cells. (biomedcentral.com)
  • 9AA treatment resulted in inhibition of HIV LTR transcription in a specific manner that was highly dependent on the presence and location of the amino moiety. (biomedcentral.com)
  • Furthermore, we observed p21WAF1 in complex with cyclin T1 and cdk9 in vitro , suggesting a direct role of p21WAF1 in HIV transcription inhibition. (biomedcentral.com)
  • An additional N‐terminal 12‐amino‐acid region (kinase inhibitory region) of JAB also contributes to high‐affinity binding to the JAK2 tyrosine kinase domain and is required for inhibition of JAK2 signaling and kinase activity. (embopress.org)
  • The abundance of the transcript of this gene was found to oscillate in a cell-cycle dependent manner with the lowest expression at mid G1 and a maximal expression during S phase. (wikipedia.org)
  • Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene . (wikipedia.org)
  • The protein encoded by this gene is a member of the Ser/Thr protein kinase family . (wikipedia.org)
  • This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product ( Rb ). (wikipedia.org)
  • Gene Ontology (GO) annotations related to this gene include protein kinase binding and cyclin-dependent protein serine/threonine kinase inhibitor activity . (genecards.org)
  • It's also possible that C/EBPα and/or C/EBPε transcription factors control the gene expression … More of these CDK inhibitors. (nii.ac.jp)
  • G-CSF dependent expression of ERO1-L gene appeared to be in control of Stat3 activation during neutrophil differentiation. (nii.ac.jp)
  • Their similar biochemical activity in blocking CDK enzymes and maintaining the growth-suppressive activity of Rb predict a tumor suppression function for CDK inhibitor genes, yet only the p16 INK4a gene has been directly linked to tumor growth by genetic alterations found in human cancers ( 17 , 25 ) and by the early development of spontaneous tumors in mice lacking p16 ( 31 ). (asm.org)
  • In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. (abnova.com)
  • Outside of G 0 , the MuvB core also binds b-Myb and FoxM1 to drive relevant cell-cycle-dependent gene expression ( 14 ). (aacrjournals.org)
  • c-Kit, the gene product of the W locus is a receptor tyrosine kinase that regulates the survival, growth and differentiation of spermatogonial cells (SGCs). (alliedacademies.org)
  • One such gene is c-kit, a 150 kDa transmembrane receptor tyrosine kinase (RTK) whose ligand is stem cell factor (SCF) (Manova et al, 1993). (alliedacademies.org)
  • G1/S-specific cyclin-D2 is a protein that in humans is encoded by the CCND2 gene . (wikidoc.org)
  • The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle . (wikidoc.org)
  • Germline mutations in the cyclin-dependent kinase gene CDK4 (chromosome 12q14) have been described in three melanoma families. (nih.gov)
  • Large germline deletions of 9p21 occur in these families, with the p19 gene implicated in its pathogenesis. (nih.gov)
  • G 1 CDK2 and CDK4 kinase activities were increased in both normal and neoplastic tissues derived from mice lacking individual CDK inhibitors and were synergistically stimulated by the simultaneous loss of two CDK inhibitors. (asm.org)
  • In contrast, we have shown previously that although serum-stimulated senescent HDF (IMR90) have abundant cyclin E-Cdk2 complexes, they lack cyclin E-associated kinase activity, a finding consistent with their failure to phosphorylate pRb ( 14 ). (asm.org)
  • Regulation of Cdk2 activity by activating (Thr-160) and inhibiting phosphorylations (Thr-14, Tyr-15) did not account for the lack of cyclin E-Cdk2 kinase activity in senescent cells, i.e., even though approximately one-half of the cyclin E-associated Cdk2 was phosphorylated on Thr-160, treatment with Cdc25 phosphatase to dephosphorylate Thr-14 and Tyr-15 did not increase activity. (asm.org)
  • This protein is an essential element of the cyclin A-CDK2 S-phase kinase. (nih.gov)
  • These creative ways to develop CDK inhibitors are presented along with crystal structures of these agents complexed with CDK2 to highlight differences in their binding sites and mechanisms of action. (aspetjournals.org)
  • Cyclin E forms complexes during this interval with CDK2. (biomedcentral.com)
  • Its inhibitory effect results from its binding to CDk4/6 and by this preventing the formation of the Cdk4/6-cyclin D complex. (celldeath.de)
  • Another level of regulation is their association with inhibitory partners called CKIs (Cyclin-dependent Kinase Inhibitor). (frontiersin.org)
  • Terminal erythroid differentiation is tightly coordinated with cell cycle exit, which is regulated by cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors (CDKI), yet their roles in erythropoiesis remain to be fully defined. (bloodjournal.org)
  • Members of the cyclin-dependent kinase inhibitor (CDKI) family have received much of the attention. (rupress.org)
  • PCNA is a co-factor of cyclin-D and it makes a complex with cyclin-D, a cyclin dependent kinase (CDK), and a cyclin dependent kinase inhibitor (CDKI). (biomedcentral.com)
  • Normally, cyclin interacts with cyclin-dependent kinase (CDK) to form a cyclin-CDK complex, which promotes cell cycle progression, whereas cyclin-dependent kinase inhibitor (CDKI) molecules inhibit the formation of cyclin-CDK complex, arresting cell cycle. (biomedcentral.com)
  • p15 , a target of transforming growth factor-β signaling, 16 is an inhibitor of the cyclin-dependent kinase-4 17 18 and a negative regulator of the G 1 /S progression within the cell cycle. (bloodjournal.org)
  • Using insect cells infected with baculovirus vectors and NIH 3T3 fibroblasts infected with ARF retrovirus, we determined that mouse p19 ARF can interact directly with p53, as well as with the p53 regulator mdm2. (pnas.org)
  • CDK4 is a subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (creativebiomart.net)
  • Cell cycle progression is delayed or stopped by cyclin-dependent kinase inhibitors, abbreviated CDIs, CKIs or CDKIs. (wikipedia.org)
  • It has been hypothesized that voltage-dependent K + channel activity could regulate mitogenesis in the nervous system by maintaining the membrane potential hyperpolarized, a condition necessary for progression through G1 phase restriction points ( Wonderlin and Strobl, 1996 ). (jneurosci.org)
  • and (2) cyclins and cyclin-dependent kinase inhibitors (cdkis) known to regulate cell cycle progression through this phase are affected by ion channel activity or changes in membrane potential. (jneurosci.org)
  • appeared to prevent the cell-cycle progression from G1 to S during G-CSF dependent neutrophil differentiation. (nii.ac.jp)
  • PKA (Protein Kinase-A) is a second messenger-dependent enzyme that has been implicated in a wide range of cellular processes, including transcription, metabolism, cell cycle progression and. (qiagen.com)
  • Cell cycle progression is driven by specific combinations of heterodimeric cyclin/CDK (cyclin-dependent kinase) complexes that license progression from one cell cycle phase to the next. (frontiersin.org)
  • CDKN2 deletion is frequently acquired during Ph-positive ALL progression and serves as a poor prognostic marker of long-term outcome in Ph-positive ALL patients with CDKN2 deletion even after the second-generation tyrosine kinase inhibitor treatment. (biomedcentral.com)
  • The Cdk:cyclin complexes of the G1/S transition regulate the progression of cells into the S phase by phosphorylating the retinoblastoma protein (Rb). (diva-portal.org)
  • As one example, we have only recently learned that loss of the platelet-derived growth factor (PDGF) receptor-α in adult human β-cells, with the resultant loss of ability to activate mitogen-activated protein kinase and methylation (Ezh2) and downstream cell cycle (p16) machinery, may underlie the refractoriness of human β-cells to proliferation ( 16 ). (diabetesjournals.org)
  • The irreversible G 1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G 1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). (asm.org)
  • Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16. (asm.org)
  • In the studies presented here we demonstrate that JAB specifically binds to the tyrosine residue (Y1007) in the activation loop of JAK2, whose phosphorylation is required for activation of kinase activity. (embopress.org)
  • [5] Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. (wikipedia.org)
  • Two critical pathways are delta-like 4 (DLL4)/Notch and BMP9/activin-like kinase-1 (ALK1), which can display cooperative signal transduction 1 , 2 and inhibit hypersprouting to maintain appropriate capillary density. (ahajournals.org)
  • The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (biomedcentral.com)
  • Another level of cell cycle regulation is affected by the cdk inhibitors, which bind to cdk or cdk-cyclin complexes and inhibit their kinase activity. (biomedcentral.com)
  • Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. (uniprot.org)
  • Conceptually, genes that negatively regulate the growth-suppressing activity of either p53 or pRb may be proto-oncogenes, as exemplified by the observation that MDM2 ( 26 ) and cyclin D1 ( 20 ), negative regulators of p53 and pRb, respectively, are frequently activated in human cancers and promote tumor growth when targeted for transgenic expression in mouse mammary tissues ( 22 , 35 ). (asm.org)
  • Cyclins function as regulators of cyclin-dependent kinases. (wikidoc.org)
  • However, compared with other kinases, little is known about cellular regulators of the JAKs. (embopress.org)
  • Caspase-dependent proteolysis of PARP-1 results in the formation of a 24 kDa DNA binding domain (DBD) and a 89 kDa catalytic fragment. (celldeath.de)
  • Tissue inhibitor of metalloproteinase-1 (TIMP-1) regulates mesenchymal stem cells through let-7f microRNA and Wnt/β-catenin signaling. (uni-muenchen.de)
  • The Janus family of protein tyrosine kinases (JAKs) regulate cellular processes involved in cell growth, differentiation and transformation through their association with cytokine receptors. (embopress.org)
  • The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16 INK4a . (wikipedia.org)
  • Up-regulated genes in MM1.S cells (multiple myeloma) treated with adaphostin [PubChem=387042] , a tyrosine kinase inhibitor with anticancer properties. (broadinstitute.org)
  • Frequency relapses are common in Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) following tyrosine kinase inhibitors (TKIs). (biomedcentral.com)
  • Results showed that no difference occurred between patients with CDKN2 deletion (44/135) and wild-type patients in sex, age, and complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs). (biomedcentral.com)
  • Tyrosine kinase inhibitors (TKIs) were currently used as front line chemotherapy agents in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) patients. (biomedcentral.com)
  • Our studies define a novel type of regulation of tyrosine kinases and might provide a basis for the design of specific tyrosine kinase inhibitors. (embopress.org)
  • PAPbeta, a protein that binds to and is phosphorylated by the non-receptor tyrosine kinase PYK2, contains several modular signaling domains including a pleckstrin homology domain, an SH3 domain, ankyrin repeats and an ARF-GAP domain. (embl-heidelberg.de)
  • Integration is at random except in rare cases in which HBV integration at specific sites has been shown to activate endogenous genes such as retinoic acid b- receptor, cyclin A, mevalonate kinase and SERCA-1. (atlasgeneticsoncology.org)
  • In contrast, the exon 1β-2-3 transcript encodes p19 ARF , which bears no homology to p16 INK4a and is composed of a 64-amino acid N-terminal domain derived from exon-1β and 105 C-terminal amino acids encoded by the alternative reading frame of exon 2. (pnas.org)
  • p21 (-/-) and wild-type (WT) FLS were compared with respect to migration towards chemoattractants found in RA synovial fluid in the presence and absence of cell cycle inhibitors. (biomedcentral.com)
  • 1997 ) Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27Kip1. (biologists.org)
  • The presence of two families of seven distinct mammalian cyclin-dependent kinase (CDK) inhibitor genes is thought to mediate the complexity of connecting a variety of cellular processes to the cell cycle control pathway. (asm.org)
  • The distinct pattern of tissue expression of CDK inhibitor genes suggests that they may function as tumor suppressors with different tissue specificities. (asm.org)
  • Our results suggest that functional collaborations between distinct CDK inhibitor genes are tissue specific and confer yet another level of regulation in cell growth control and tumor suppression. (asm.org)
  • Two families of cyclin-dependent kinase (CDK) inhibitors, totaling seven genes, have been identified in mammalian cells. (asm.org)
  • Neither mutational analysis in human tumors nor phenotypic examination of genetically targeted mice lacking any of the other individual CDK inhibitor genes has provided strong evidence for a direct role for any of the other CDK inhibitors as tumor suppressors. (asm.org)
  • Using quantitative chromatin immunoprecipitation and expression assays, we show that FoxM1 is essential for transcription of the mitotic regulatory genes Cdc25B, Aurora B kinase, survivin, centromere protein A (CENPA), and CENPB. (jax.org)
  • The antiproliferative effects of K + channel blockers and veratridine were still present in OP cells isolated from INK4a −/− mice, lacking the cyclin-dependent kinase inhibitors p16 INK4a and p19 ARF . (jneurosci.org)
  • Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. (wikipedia.org)
  • 5-Azacytidine and 5-Aza-2′-deoxycytidine (decitabine), 2 potent inhibitors of cytosine methylation, 8 have shown strong antileukemic activity 9 in acute myeloid leukemia (AML). (bloodjournal.org)
  • This indicates that an increase in G 1 CDK kinase activity is a critical step during but is not sufficient for tumor growth. (asm.org)
  • 13 ]. This pattern suggested that the growth promoting cyclin/CDK activity was counteracted by CDK inhibitors and this could explain the low frequency of proliferating cells identified by Ki67 and cyclin A staining (typically less than 8 and 4 percent, resp. (hindawi.com)
  • Flavopiridol is a potent cyclin-dependent kinase inhibitor with preclinical activity against non-small cell lung cancer (NSCLC), inhibiting tumor growth in vitro and in vivo by cytostatic and cytotoxic mechanisms. (aacrjournals.org)
  • Similarly, DLL4 activity was suppressed when the basal activin-like kinase-1-Smad1/5/9 pathway was inhibited, showing that these pathways are interdependent. (ahajournals.org)
  • Conclusions- DLL4/Notch and BMP9/activin-like kinase-1 signaling rely on each other's pathways for full activity. (ahajournals.org)
  • Using caspase inhibitors, as well as caspase-resistant mutants of c-Abl (TM-c-Abl and D565A-Abl), we then showed that c-Abl cleavage in MM cells requires caspase activity. (broadinstitute.org)
  • are not involved in ion channel-dependent cell cycle arrest in OP cells. (jneurosci.org)
  • Binding of p19 ARF to p53 requires the ARF N-terminal domain (amino acids 1-62) that is necessary and sufficient to induce cell cycle arrest. (pnas.org)
  • Overexpression of p19 ARF in wild type or ARF -null mouse embryo fibroblasts increases the half-life of p53 from 15 to ≈75 min, correlating with an increased p53-dependent transcriptional response and growth arrest. (pnas.org)
  • The p19 ARF protein can induce both G 1 and G 2 phase arrest ( 2 ) in a manner that depends on functional p53 ( 14 ). (pnas.org)
  • Mechanistically, loss of PTPMT1 decreased mitochondrial aerobic metabolism by limiting utilization of pyruvate, which resulted in bioenergetic stress in neural precursor/stem cells but not in progenitor or mature cells, leading to cell cycle arrest through activation of the AMPK-p19/p21 pathway. (sciencemag.org)
  • Enforced expression of cyclin D3 abrogated the PTEN-induced cell cycle arrest. (aacrjournals.org)
  • Studies with oligodendrocyte progenitor cells from INK4a−/− mice indicated that the G1 cyclin kinase inhibitor p16(INK4a) as well as p19(ARF)were not required for agonist-stimulated proliferation arrest. (biologists.org)
  • A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. (harvard.edu)
  • In addition to its most well-known role as a cdk inhibitor (CKI) that can lead to cell cycle arrest, p21WAF1 is also well recognized to be involved in a variety of other physiological functions. (biomedcentral.com)
  • Overexpression of any of the cdk inhibitors will induce G1-cell cycle arrest [ 3 ]. (biomedcentral.com)
  • Stat3 activation is known to be necessary for G-CSF dependent neutrophil differentiation. (nii.ac.jp)
  • This mechanism seems to accelerate G-CSF dependent neutrophil differentiation. (nii.ac.jp)
  • The purpose of this review is to provide a broad overview of the development of various classes of CDK inhibitors. (aspetjournals.org)
  • Two major classes of CDK inhibitors have been identified. (biomedcentral.com)
  • CDKN2C ‏ ( Cyclin dependent kinase inhibitor 2C ) هوَ بروتين يُشَفر بواسطة جين CDKN2C في الإنسان . (wikipedia.org)
  • One reason for this is that cell number variation between different CNS tissues is also dependent on processes that are distinct from proliferation. (biologists.org)
  • p19ARF counters uncontrolled proliferation and oncogenic signals in p53 dependent pathways. (novusbio.com)
  • Importantly, virus replication was found to be inhibited in HIV-1 infected cell lines by 9AA in a dose-dependent manner without inhibiting cellular proliferation or inducing cell death. (biomedcentral.com)