Cyclin dependent kinase inhibitor p19. Medical search

A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.

A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.

Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.

A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.

Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.

A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.

The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.

Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.

High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.

A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.

Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.

A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.

A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.

All of the processes involved in increasing CELL NUMBER including CELL DIVISION.

Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.

A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.

One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.

A potent inhibitor of CYCLIN-DEPENDENT KINASES in G1 PHASE and S PHASE. In humans, aberrant expression of p57 is associated with various NEOPLASMS as well as with BECKWITH-WIEDEMANN SYNDROME.

A cell line derived from cultured tumor cells.

Agents that inhibit PROTEIN KINASES.

A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.

The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.

A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.

A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.

A cyclin subtype that is specific for CYCLIN-DEPENDENT KINASE 4 and CYCLIN-DEPENDENT KINASE 6. Unlike most cyclins, cyclin D expression is not cyclical, but rather it is expressed in response to proliferative signals. Cyclin D may therefore play a role in cellular responses to mitogenic signals.

Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.

A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION.

A cyclin subtype that binds to the CYCLIN-DEPENDENT KINASE 3 and CYCLIN-DEPENDENT KINASE 8. Cyclin C plays a dual role as a transcriptional regulator and a G1 phase CELL CYCLE regulator.

The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.

A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.

Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.

Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.

The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.

A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.

An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN-LIKE REPEATS. Aberrant expression of this protein has been associated with deregulated EPITHELIAL CELL growth, organ enlargement, and a variety of NEOPLASMS.

Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.

Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.

Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.

The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.

A cyclin D subtype which is regulated by GATA4 TRANSCRIPTION FACTOR. Experiments using KNOCKOUT MICE suggest a role for cyclin D2 in granulosa cell proliferation and gonadal development.

Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.

Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.

Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.

An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.

A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.

A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.

A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.

The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.

Established cell cultures that have the potential to propagate indefinitely.

A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.

A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.

The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.

A transcription factor that possesses DNA-binding and E2F-binding domains but lacks a transcriptional activation domain. It is a binding partner for E2F TRANSCRIPTION FACTORS and enhances the DNA binding and transactivation function of the DP-E2F complex.

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.

An INK4 cyclin-dependent kinase inhibitor containing four ANKYRIN-LIKE REPEATS. INK4B is often inactivated by deletions, mutations, or hypermethylation in HEMATOLOGIC NEOPLASMS.

Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.

A cyclin G subtype that is constitutively expressed throughout the cell cycle. Cyclin G1 is considered a major transcriptional target of TUMOR SUPPRESSOR PROTEIN P53 and is highly induced in response to DNA damage.

An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.

A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.

A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

Transport proteins that carry specific substances in the blood or across cell membranes.

Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.

Substances that inhibit or prevent the proliferation of NEOPLASMS.

Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.

A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN REPEATS. Aberrant expression of this protein has been associated with TESTICULAR CANCER.

A family of structurally-related proteins that were originally identified by their ability to complex with cyclin proteins (CYCLINS). They share a common domain that binds specifically to F-BOX MOTIFS. They take part in SKP CULLIN F-BOX PROTEIN LIGASES, where they can bind to a variety of F-BOX PROTEINS.

A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.

Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.

A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.

The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.

A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.

Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.

The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.

Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.

The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.

Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.

A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).

A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.

A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.

DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.

Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.

A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.

Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.

Elements of limited time intervals, contributing to particular results or situations.

A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.

Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)

A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.

A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.

Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.

Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.

BENZOIC ACID amides.

The rate dynamics in chemical or physical systems.

A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.

Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.

Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.

The relationship between the dose of an administered drug and the response of the organism to the drug.

A cyclin B subtype that colocalizes with GOLGI APPARATUS during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.

A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

A group of phenyl benzopyrans named for having structures like FLAVONES.

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)

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

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

"Entrez Gene: CDKN2D cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4)". Dehkordi, Shiva Kazempour; Walker, Jamie; Sah, ... 1995). "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. ... 2004). "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27( ... Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene. The protein encoded by this ...

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

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. ...

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

... 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 ...

https://en.wikipedia.org/wiki/Cyclin_D2

"Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ... CDKN2C has been shown to interact with Cyclin-dependent kinase 4 and Cyclin-dependent kinase 6. GRCh38: Ensembl release 89: ... Cyclin-dependent kinase 4 inhibitor C is an enzyme that in humans is encoded by the CDKN2C gene. The protein encoded by this ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". Ewing RM, Chu P, Elisma F, Li H, Taylor P, ...

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

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 ...

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

The p16 protein is a cyclin dependent kinase inhibitor (CDK) inhibitor and it activates Rb tumor suppressor. p16 binds to CDK 4 ... Analyzing single nucleus RNA-Seq data from human brains suggested p19 as a marker for senescent neurons, which are strongly ... p16Ink4a also activates pRB, but through inactivation of cyclin-dependent kinase 4 (Cdk 4) and cyclin-dependent kinase 6 (Cdk 6 ... p53 activates p21 which deactivates cyclin-dependent kinase 2(Cdk 2). Without Cdk 2, retinoblastoma protein (pRB) remains in ...

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

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 ...

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

... 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. ...

https://en.wikipedia.org/wiki/MAZ_(gene)

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 ...

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

... 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 ...

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

"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 ...

https://en.wikipedia.org/wiki/S-phase_kinase-associated_protein_1

Inhibitors of the MDM2-p53 interaction include the cis-imidazoline analog nutlin. Levels and stability of Mdm2 are also ... Honda R, Yasuda H (March 2000). "Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger ... This loop can be interfered with by kinases and genes like p14arf when p53 activation signals, including DNA damage, are high. ... Zhao L, Samuels T, Winckler S, Korgaonkar C, Tompkins V, Horne MC, Quelle DE (January 2003). "Cyclin G1 has growth inhibitory ...

https://en.wikipedia.org/wiki/Mdm2

July 2007). "Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation". Nature ... NMDAR/TRPM4 interaction interface inhibitors (also known as interface inhibitors) disrupt the NMDAR/TRPM4 complex and detoxify ... "A critical importance of polyamine site in NMDA receptors for neurite outgrowth and fasciculation at early stages of P19 ... Calcium/calmodulin-dependent protein kinases Laube B, Hirai H, Sturgess M, Betz H, Kuhse J (March 1997). "Molecular ...

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

Cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors (CDKIs) regulate cell-cycle progression. CDK activity is modulated ... by the CDKIs p27kip1, p57kip2, p16ink4A, p15ink4B, p18ink4C, and p19ink4D. Although CDKN2A (which encodes p16ink4A) is not ... Cell-cycle control proteins are commonly dysregulated in pituitary tumors, usually by epigenetic silencing of inhibitors of ...

https://www.medscape.com/viewarticle/530480_7

Cyclin-Dependent Kinase Inhibitor p19 / genetics Actions. * Search in PubMed * Search in MeSH ...

https://pubmed.ncbi.nlm.nih.gov/33428330/

Control of spermatogenesis in mice by the cyclin D-dependent kinase inhibitors p18(Ink4c) and p19(Ink4d).. Zindy F; den Besten ... 1. Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) ... Expression patterns of cyclins D1, E and cyclin-dependent kinase inhibitors p21(Waf1/Cip1) and p27(Kip1) in urothelial ... Regulation of cyclin dependent kinase inhibitor proteins during neonatal cerebella development.. Watanabe G; Pena P; Shambaugh ...

https://pubmedhh.nlm.nih.gov/biomarkers/search.php?id=12698196&mod=related&page=1&from=&outid=&proj=

The senescent neurons also had high levels of a protein called cyclin-dependent kinase inhibitor 2D (CDKN2D/p19), which helps ... Profiling senescent cells in human brains reveals neurons with CDKN2D/p19 and tau neuropathology. Nature Aging. 2021;1:1107- ...

https://www.nia.nih.gov/news/senescent-brain-cells-may-contribute-alzheimers-disease

Review of alterations of the cyclin-dependent kinase inhibitor INK4 family genes p15, p16, p18 and p19 in human leukemia- ...

https://www.ncbi.nlm.nih.gov/pubmed/?term=28196408

Cyclin Dependent Kinase Inhibitor 2D Cyclin Dependent Kinase Inhibitor p19 Cyclin-Dependent Kinase Inhibitor 2D INK4D Protein ... Cyclin Dependent Kinase Inhibitor 2D. Cyclin Dependent Kinase Inhibitor p19. Cyclin-Dependent Kinase Inhibitor 2D. INK4D ... Cyclin-Dependent Kinase Inhibitor p19 - Preferred Concept UI. M0477673. Scope note. An INK4 cyclin-dependent kinase inhibitor ... Protein Kinase Inhibitors. Public MeSH Note:. 2006; CYCLIN-DEPENDENT KINASE INHIBITOR P19 was indexed under CARRIER PROTEINS ...

https://decs.bvsalud.org/en/ths/resource/?id=50930

Cyclin-Dependent Kinase Inhibitor p19 [D12.776.624.776.355.400] * Cyclin-Dependent Kinase Inhibitor p21 [D12.776.624.776. ... Cyclin-Dependent Kinase Inhibitor Proteins [D12.644.360.225] * Cyclin-Dependent Kinase Inhibitor p15 [D12.644.360.225.100] ... Cyclin-Dependent Kinase Inhibitor Proteins [D12.776.167.187] * Cyclin-Dependent Kinase Inhibitor p15 [D12.776.167.187.100] ... Cyclin-Dependent Kinase Inhibitor Proteins [D12.776.476.225] * Cyclin-Dependent Kinase Inhibitor p15 [D12.776.476.225.100] ...

https://meshb-prev.nlm.nih.gov/record/ui?ui=D050764

https://meshb.nlm.nih.gov/record/ui?ui=D050764

cyclin-dependent kinase 4 inhibitor A. *cyclin-dependent kinase inhibitor 2A. *cyclin-dependent kinase inhibitor 2A (melanoma, ... and pancreatic cancers in addition to melanoma risk in families bearing the cyclin-dependent kinase inhibitor 2A mutation: ... cyclin-dependent kinase inhibitor 2A isoform p12. *cyclin-dependent kinase inhibitor 2A isoform p14ARF ... cyclin-dependent kinase inhibitor 2A isoform p16gamma. *cyclin-dependent kinase inhibitor 2A isoform p16INK4a ...

https://medlineplus.gov/genetics/gene/cdkn2a/

Cyclin-dependent kinase 4 inhibitor A. *Cyclin-dependent kinase inhibitor 2A, isoforms 1/2/3 ... p19. Description. From NCBI Gene: This gene (CDKN2A) generates several transcript variants which differ in their first exons. ... 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, ...

https://edrn.nci.nih.gov/data-and-resources/biomarkers/cdkn2a-p16/

D12.776.476.225.300 Cyclin-Dependent Kinase Inhibitor p19 D12.644.360.225.400 D12.776.476.225.400 Cyclin-Dependent Kinase ... D12.776.476.262.180 Cyclin-Dependent Kinase Inhibitor p15 D12.644.360.225.100 D12.776.476.225.100 Cyclin-Dependent Kinase ... D12.776.476.225.500 Cyclin-Dependent Kinase Inhibitor p27 D12.644.360.225.600 D12.776.476.225.600 Cyclin-Dependent Kinase ... D12.776.476.225.700 Cyclin-Dependent Kinase Inhibitor Proteins D12.644.360.225 D12.776.476.225 Cyclins D23.348.353 D12.644. ...

https://nlmpubs.nlm.nih.gov/projects/mesh/.newterms/mnchg2007.txt

Cyclin-Dependent Kinase Inhibitor p18 N0000170190 Cyclin-Dependent Kinase Inhibitor p19 N0000170188 Cyclin-Dependent Kinase ... Cyclin-Dependent Kinase 9 N0000170189 Cyclin-Dependent Kinase Inhibitor p15 N0000170193 Cyclin-Dependent Kinase Inhibitor p16 ... Cyclin-Dependent Kinase Inhibitor p27 N0000170191 Cyclin-Dependent Kinase Inhibitor p57 N0000170186 Cyclin-Dependent Kinase ... Cyclin E N0000170543 Cyclin-Dependent Kinase 2 N0000170542 Cyclin-Dependent Kinase 4 N0000170547 Cyclin-Dependent Kinase 5 ...

https://evs.nci.nih.gov/ftp1/FDA/ndfrt/Archive/StructuralClass%202007-10-09.txt

This protein has been shown to form a stable complex with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus ... The abundance of the transcript of this gene was found to oscillate in a cell-cycle dependent manner with the lowest expression ... The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. ... The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein has been ...

https://pharos.nih.gov/targets/CDKN2D

C21 p27Kip1 can be phosphorylated by Cyclin E or Cyclin A dependent kinases and thereby may be targeted for degradation (Sheaff ... P19 CK2 phosphorylates murine Ser389 (human 392) (Kapoor and Lozano, 1998).. P20 PCAF acetylates p53 Lys320 (Sakaguchi et al., ... thereby perhaps blocking the binding of an unidentified inhibitor. No c-Myc recognition element is required for activation of ... C12 When phosphorylated by Cyclin D-dependent kinases, DMP1 activates transcription (Hirai and Sherr, 1996). ...

https://discover.nci.nih.gov/mim/kohnk/annotations.jsp

D23.50.301.264.35.281 Cyclin-Dependent Kinase 9 D8.811.641.752 Cyclooxygenase 2 Inhibitors D27.505.954.329.30.500.500 ... D23.529.374.465.550 Interleukin-23 Subunit p19 D23.529.374.465.759.500 D23.529.374.465.550.500 Iodocyanopindolol D2.33.100.624. ... NAD-Dependent D8.811.682.47.385.415.250 D8.811.682.47.820.150.415.250 Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent ... A11.329.228.100.775.800 A Kinase Anchor Proteins D12.776.157.57.03 Acebutolol D2.33.100.624.25 D2.33.755.624.25 Acellular ...

https://decs2018.bvsalud.org/P/mnchg2014.txt

https://decs2014.bvsalud.org/I/mnchg2014.txt

https://decs2019.bvsalud.org/P/mnchg2014.txt

https://decs2016.bvsalud.org/P/mnchg2014.txt

https://decs2015.bvsalud.org/P/mnchg2014.txt

https://decs2020.bvsalud.org/P/mnchg2014.txt

https://decs2017.bvsalud.org/P/mnchg2014.txt

... of cyclin-dependent kinase inhibitor 2 A (CDKN2A), which results in the immunohistochemical loss of p16 frequently found in CM ... resulting in reduced H3K4 methylation and low expression levels of the locus-encoded tumor suppressors p16/Ink4a and p19/Arf. ... BACKGROUND/AIM: CDK inhibitor p16 plays a pivotal role in the induction of cellular senescence and functions as a tumor ... thyroid tumorigenesis and progression and CDK4 inhibitors will be effective for treatment of INK4-inactivated or cyclin D- ...

https://pesquisa.bvsalud.org/portal/?lang=pt&q=mh:Inibidor+p16+de+Quinase+Dependente+de+Ciclina/metabolismo

Tyrosine kinase inhibitors. Inhibitors of the EGFR tyrosine kinase have the theoretical advantage of also blocking activating ... Cyclin D1 is an important tumor suppressor gene product involved in regulating the cell cycle. Overexpression of cyclin D1 has ... The INK4 family of genes (p15, p16, p18, p19) regulates the presynthetic gap (G1) phase (phase of cells prior to DNA synthesis ... The specificity and potency of the signaling output from activated EGFR is highly dependent on the type of activating ligand, ...

https://emedicine.staging.medscape.com/article/854971-overview

Cyclin-dependent kinases are believed to be responsible for H1 phosphorylation (Swank et al. 1997). Several kinases are able to ... Liu J and Bain L (2014) Arsenic inhibits hedgehog signaling during P19 cell differentiation, Toxicology and Applied ... 2008). The level of inhibition is comparable with that of the well-known HDAC inhibitor trichostatin A (Drummond et al. 2005). ... Four distinct cyclin-dependent kinases phosphorylate histone H1 at all of its growth-related phosphorylation sites. ...

https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.1002114

... p25 np5 p24 np4 nnr p23 np3 fructokinases p22 nnp p21 hodgsonii nno np1 p20 nnm nni nnd nnc yiqi pierced hamiltoni nmy nmx p19 ... replicator oxobut sulfadimethoxine nek9 nek8 nek7 nek6 nek3 nek2 nek1 hopeaphenol doxil acariformes pyrimidinethione kinase ... surfeit cytoskyrin embellisia tetrahydropyrazolo galaxea ciconia prunes bambusa cbln4 cbln3 cbln2 cbln1 capitis dependent ... constitutes frontolimbic ched1 cefixime coyote neocnidilide hypopituitary bromopyridyl cheat trinitrin biology further cyclins ...

https://lexsrv3.nlm.nih.gov/LexSysGroup/Projects/tc/2008/docs/data/Jdi/restrictWords.txt

4. Protein folding and stability of human CDK inhibitor p19(INK4d). (nih.gov)
6. Folding mechanism of an ankyrin repeat protein: scaffold and active site formation of human CDK inhibitor p19(INK4d). (nih.gov)
The senescent neurons also had high levels of a protein called cyclin-dependent kinase inhibitor 2D ( CDKN2D/ p19), which helps control whether a cell divides. (nih.gov)
The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. (biolinkk.com)
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. (biolinkk.com)
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. (lookformedical.com)
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. (lookformedical.com)
It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. (lookformedical.com)
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.de)
This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein. (nih.gov)
B3 Ku binds to the C-terminal region of DNA-PK (amino acids 3002-3850) near the protein kinase domain (Jin et al. (nih.gov)
Bim, a proapoptotic protein, up-regulated via transcription factor E2F1-dependent mechanism, functions as a prosurvival molecule in cancer. (univ-paris5.fr)

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. (nih.gov)
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. (nih.gov)
After mitogenic initiation, synthesized D-type cyclins bind to and activate Cdk4 and Cdk6. (walshmedicalmedia.com)

8. Evidence of a role for the INK4 family of cyclin-dependent kinase inhibitors in ovarian granulosa cell tumors. (nih.gov)
14. Expression of INK4 inhibitors of cyclin D-dependent kinases during mouse brain development. (nih.gov)
20. INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions. (nih.gov)
An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN REPEATS . (nih.gov)
It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. (lookformedical.com)
The cell cycle process is regulated by the sequential expression, activation, and inhibition of Cyclin-dependent kinases (CDKs) associated with activating subunits, the cyclins, as well as two families of Cyclin-dependent kinase inhibitors (CKIs)-the Kip/Cip family of proteins (p21, p27 and p57) and the INK4 family (p16, p15, p19 and p18) [ 1 - 3 ]. (walshmedicalmedia.com)

3. Structure of human cyclin-dependent kinase inhibitor p19INK4d: comparison to known ankyrin-repeat-containing structures and implications for the dysfunction of tumor suppressor p16INK4a. (nih.gov)
9. Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d. (nih.gov)
18. NMR structural characterization of the CDK inhibitor p19INK4d. (nih.gov)

1997) . c-Abl tyrosine kinase activity is stimulated in response to ionizing radiation, ara-C, camptothecin, or etoposide (Yuan et al. (nih.gov)
In addition to their estrogenic activity, many of these plant compounds can interfere with steroid metabolism and bioavailability and can also inhibit enzymes, such as tyrosine kinase or topoisomerase, which are important for cellular proliferation. (marysfamilymedicine.org)

5. Molecular cloning, expression pattern, and chromosomal localization of human CDKN2D/INK4d, an inhibitor of cyclin D-dependent kinases. (nih.gov)

Recombinant Human p19 INK4d GST (N. (novusbio.com)
Learn more about PTMs related to p19 INK4d. (novusbio.com)
Discover related pathways, diseases and genes to p19 INK4d. (novusbio.com)
1. Backbone dynamics of the CDK inhibitor p19(INK4d) studied by 15N NMR relaxation experiments at two field strengths. (nih.gov)
10. Control of spermatogenesis in mice by the cyclin D-dependent kinase inhibitors p18(Ink4c) and p19(Ink4d). (nih.gov)
15. Alterations of the cyclin-dependent kinase inhibitor p19 (INK4D) is rare in hematopoietic malignancies. (nih.gov)

Cyclin dependent kinase inhibitor proteins. (lookformedical.com)
A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. (lookformedical.com)
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. (lookformedical.com)
A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. (lookformedical.com)

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. (lookformedical.com)
Oncogenically activated Ras inhibits the TGFbeta-induced nuclear accumulation of Smad2 and Smad3 and Smad-dependent transcription. (sdbonline.org)

Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. (lookformedical.com)
1997) . c-Abl-dependent phosphorylation of DNA-PK is stimulated by ionizing radiation (Kharbanda et al. (nih.gov)
Ras acting via Erk MAP kinases causes phosphorylation of Smad2 and Smad3 at specific sites in the region linking the DNA-binding domain and the transcriptional activation domain. (sdbonline.org)

Considerable improvements in gene expression underlie the biological results of Kaiso knock down The result shows a international alter affecting the ex pression of numerous genes critical in hematopoietic differentiation Inhibitors,Modulators,Libraries and proliferation, coherently using the genome broad transcriptional response to Kaiso, character ized during early vertebrate development. (phosphatases.com)

Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms. (lookformedical.com)
This downregulation of a specific cell-cycle-regulating microRNA is dependent on the translocation of the bacterial effector CagA into the host cells, a mechanism highly associated with the development of severe atrophic gastritis and intestinal-type gastric carcinoma. (biomedcentral.com)

C2 The Cyclin E and A genes (but not the Cyclin D gene) are strongly activated by E2F1 (DeGregori et al. (nih.gov)

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. (biolinkk.com)
Overexpression of pRb can increase the expression Cyclin D1 by an unknown mechanism (Watanabe et al. (nih.gov)

As a proline directed serine/threonine kinase, Cdk5 is structurally most similar to CDC2 (Cdk1), but it functionally differs from traditional Cdks [ 8 ]. (walshmedicalmedia.com)

In addition to a constitutively occupied E2F1-Sp1 site immediately upstream of the cyclin E transcription start region, there is downstream a cell cycle-regulated site (termed CERM) that may function as a cyclin E-repressor module. (nih.gov)

The p35 and p39 share no homology to cyclins at the amino acid level but have remarkable structural similarity all the same [ 8 ]. (walshmedicalmedia.com)

A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. (lookformedical.com)
Cyclin-dependent kinase 5 (Cdk5) is described as an atypical Cdk, which has been shown to have no cell cycle promoting activity. (walshmedicalmedia.com)
Later, in M phase, Cyclin B/Cdk1 activation is triggered allowing the cell to proceed through cytokinesis. (walshmedicalmedia.com)

A subset of cyclins may also function as transcriptional regulators. (lookformedical.com)

The cyclin E/Cdk2 complex is required for transition from G1 to S phase. (walshmedicalmedia.com)

Mutation of these MAP kinase sites in Smad3 yields a Ras-resistant form that can rescue the growth inhibitory response to TGFbeta in Ras-transformed cells. (sdbonline.org)

this interaction does not require c-Abl kinase activity. (nih.gov)
B10 HMG1 or 2 compete with Ku for binding to DNA-PK and stimulate DNA-dependent kinase activity in vitro in the absence of Ku (Yumoto et al. (nih.gov)

Several of the traditional cyclins can bind with Cdk5, but none can activate it. (walshmedicalmedia.com)

Cyclin-dependent kinase 5 (Cdk5) is a unique member of the Cdk family, despite the fact that its cloning was based on its sequence homology to other Cdks [ 8 ]. (walshmedicalmedia.com)

It is an endogenous inhibitor of RAF KINASES and may play a role in regulating SIGNAL TRANSDUCTION. (lookformedical.com)
A ubiquitously expressed raf kinase subclass that plays an important role in SIGNAL TRANSDUCTION. (lookformedical.com)

There are ten Cdks and nine cyclins in mammal tissues that have been described to date. (walshmedicalmedia.com)

Anatomy7

Organisms2

Chemicals and Drugs72

Analytical, Diagnostic and Therapeutic Techniques and Equipment5

Phenomena and Processes29

Disciplines and Occupations1

Information Science3

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

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)

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

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

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

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

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

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

No images available that match "cyclin dependent kinase inhibitor p19"

Cyclin-Dependent Kinase Inhibitor p27

Cyclin-Dependent Kinase Inhibitor p21

Cyclin-Dependent Kinases

Cyclins

Cell Cycle Proteins

Cyclin-Dependent Kinase Inhibitor p16

Cell Cycle

Tumor Suppressor Proteins

Microtubule-Associated Proteins

Cyclin-Dependent Kinase 2

Cyclin D1

Cyclin A

Cyclin E

Cell Proliferation

Cyclin-Dependent Kinase 4

CDC2-CDC28 Kinases

Apoptosis

Cyclin-Dependent Kinase Inhibitor p57

Cell Line, Tumor

Protein Kinase Inhibitors

Protein-Serine-Threonine Kinases

G1 Phase

Cyclin-Dependent Kinase 5

Cyclin B

Cyclin D

CDC2 Protein Kinase

Cyclin-Dependent Kinase Inhibitor Proteins

Cyclin C

Phosphorylation

Cyclin D3

Retinoblastoma Protein

Cyclin-Dependent Kinase 6

Cell Division

Enzyme Inhibitors

S Phase

Cyclin B1

Cyclin-Dependent Kinase Inhibitor p18

Tumor Suppressor Protein p53

Proto-Oncogene Proteins

Tumor Cells, Cultured

Signal Transduction

Cyclin D2

Cells, Cultured

Phosphatidylinositol 3-Kinases

Blotting, Western

E2F1 Transcription Factor

Cyclin A1

Protein Kinases

Purines

Transfection

Cell Line

Mitosis

Cyclin G

G2 Phase

Transcription Factor DP1

Mutation

Proliferating Cell Nuclear Antigen

Cyclin-Dependent Kinase Inhibitor p15

DNA-Binding Proteins

Cyclin G1

MAP Kinase Signaling System

Cyclin A2

E2F Transcription Factors

RNA, Messenger

Molecular Sequence Data

Carrier Proteins

Nuclear Proteins

Antineoplastic Agents

Transcription Factors

Base Sequence

Protein-Tyrosine Kinases

Calcium-Calmodulin-Dependent Protein Kinases

Immunohistochemistry

Cyclin-Dependent Kinase Inhibitor p19

S-Phase Kinase-Associated Proteins

src-Family Kinases

Enzyme Activation

Down-Regulation

Gene Expression Regulation

Protein Binding