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. (1/120)

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. (2/120)

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)

Role of PPARgamma in regulating a cascade expression of cyclin-dependent kinase inhibitors, p18(INK4c) and p21(Waf1/Cip1), during adipogenesis. (3/120)

Molecular mechanisms coupling growth arrest and cell differentiation were examined during adipogenesis. Data are presented that document a cascade expression of members of two independent families of cyclin-dependent kinase inhibitors that define distinct states of growth arrest during 3T3-L1 preadipocyte differentiation. Exit from the cell cycle into a pre-differentiation state of post-mitotic growth arrest was characterized by significant increases in p21 and p27. During onset of irreversible growth arrest associated with terminal differentiation, the level of p21 declined with a concomitant, dramatic increase in p18 and a sustained level of p27. The expression of p18 and p21, regulated at the level of protein and mRNA accumulation, was directly coupled to differentiation. Stable cell lines were engineered to express adipogenic transcription factors to examine the active role of trans-acting elements in regulating these cell cycle inhibitors. Ectopic expression of peroxisome proliferator-activated receptor (PPAR) gamma in non-precursor fibroblastic cell lines resulted in conversion to adipocytes and a coordinated increase in p18 and p21 mRNA and protein expression in a PPARgamma ligand-associated manner. These data demonstrate a role for PPARgamma in mediating the differentiation-dependent cascade expression of cyclin-dependent kinase inhibitors, thereby providing a molecular mechanism coupling growth arrest and adipocyte differentiation.  (+info)

Down-regulation of the INK4 family of cyclin-dependent kinase inhibitors by tax protein of HTLV-1 through two distinct mechanisms. (4/120)

Tax oncoprotein of human T-cell leukemia virus type 1 (HTLV-1) affects multiple regulatory processes of infected cells through activation and repression of specific transcription and also through modulation of functions of cell cycle regulators. Previously, we found that Tax binds to p16ink4a, a member of the INK4 family of cyclin-dependent kinase inhibitors, and counteracts its inhibitory activity, resulting in cell cycle progression. In this study, we examined the effects of Tax on other members of the INK4 family and found that Tax can bind to p15ink4b similarly to p16ink4a, but not to p18ink4c and p19ink4d. Tax binding to p15ink4b inactivated its function and restored CDK4 kinase activity. Accordingly, Tax-expressing cells became resistant to p15ink4b-mediated growth arrest induced by TGFbeta. On the other hand, expression of p18ink4c was transcriptionally repressed by Tax through the E-box element of the promoter, which may contribute to the marked reduction of p18ink4c mRNA in HTLV-1-infected T-cells. These observations indicate that Tax suppresses the inhibitory activities of INK4 family members through two independent mechanisms: functional inhibition of two INK4 proteins and repression of expression of another INK4 protein. These effects may play roles in HTLV-1-induced deregulation of the cell cycle, possibly promoting cellular transformation.  (+info)

An intrinsic timer that controls cell-cycle withdrawal in cultured cardiac myocytes. (5/120)

Developing cardiac myocytes divide a limited number of times before they stop and terminally differentiate, but the mechanism that stops their division is unknown. To help study the stopping mechanism, we defined conditions under which embryonic rat cardiac myocytes cultured in serum-free medium proliferate and exit the cell cycle on a schedule that closely resembles that seen in vivo. The culture medium contains FGF-1 and FGF-2, which stimulate cell proliferation, and thyroid hormone, which seems to be necessary for stable cell-cycle exit. Time-lapse video recording shows that the cells within a clone tend to divide a similar number of times before they stop, whereas cells in different clones divide a variable number of times before they stop. Cells cultured at 33 degrees C divide more slowly but stop dividing at around the same time as cells cultured at 37 degrees C, having undergone fewer divisions. Together, these findings suggest that an intrinsic timer helps control when cardiac myocytes withdraw from the cell cycle and that the timer does not operate by simply counting cell divisions. We provide evidence that the cyclin-dependent kinase inhibitors p18 and p27 may be part of the timer and that thyroid hormone may help developing cardiac myocytes stably withdraw from the cell cycle.  (+info)

Cooperation of p27(Kip1) and p18(INK4c) in progestin-mediated cell cycle arrest in T-47D breast cancer cells. (6/120)

The steroid hormone progesterone regulates proliferation and differentiation in the mammary gland and uterus by cell cycle phase-specific actions. The long-term effect of progestins on T-47D breast cancer cells is inhibition of cellular proliferation. This is accompanied by decreased G(1) cyclin-dependent kinase (CDK) activities, redistribution of the CDK inhibitor p27(Kip1) among these CDK complexes, and alterations in the elution profile of cyclin E-Cdk2 upon gel filtration chromatography, such that high-molecular-weight complexes predominate. This study aimed to determine the relative contribution of CDK inhibitors to these events. Following progestin treatment, the majority of cyclin E- and D-CDK complexes were bound to p27(Kip1) and few were bound to p21(Cip1). In vitro, recombinant His(6)-p27 could quantitatively reproduce the effects on cyclin E-Cdk2 kinase activity and the shift in molecular weight observed following progestin treatment. In contrast, cyclin D-Cdk4 was not inhibited by His(6)-p27 in vitro or p27(Kip1) in vivo. However, an increase in the expression of the Cdk4/6 inhibitor p18(INK4c) and its extensive association with Cdk4 and Cdk6 were apparent following progestin treatment. Recombinant p18(INK4c) led to the reassortment of cyclin-CDK-CDK inhibitor complexes in vitro, with consequent decrease in cyclin E-Cdk2 activity. These results suggest a concerted model of progestin action whereby p27(Kip1) and p18(INK4c) cooperate to inhibit cyclin E-Cdk2 and Cdk4. Since similar models have been developed for growth inhibition by transforming growth factor beta and during adipogenesis, interaction between the Cip/Kip and INK4 families of inhibitors may be a common theme in physiological growth arrest and differentiation.  (+info)

Distinct versus redundant properties among members of the INK4 family of cyclin-dependent kinase inhibitors. (7/120)

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)

Limited overlapping roles of P15(INK4b) and P18(INK4c) cell cycle inhibitors in proliferation and tumorigenesis. (8/120)

Entry of quiescent cells into the cell cycle is driven by the cyclin D-dependent kinases Cdk4 and Cdk6. These kinases are negatively regulated by the INK4 cell cycle inhibitors. We report the generation of mice defective in P15(INK4b) and P18(INK4c). Ablation of these genes, either alone or in combination, does not abrogate cell contact inhibition or senescence of mouse embryo fibroblasts in culture. However, loss of P15(INK4b), but not of P18(INK4c), confers proliferative advantage to these cells and makes them more sensitive to transformation by H-ras oncogenes. In vivo, ablation of P15(INK4b) and P18(INK4c) genes results in lymphoproliferative disorders and tumor formation. Mice lacking P18(INK4c) have deregulated epithelial cell growth leading to the formation of cysts, mostly in the cortical region of the kidneys and the mammary epithelium. Loss of both P15(INK4b) and P18(INK4c) does not result in significantly distinct phenotypic manifestations except for the appearance of cysts in additional tissues. These results indicate that P15(INK4b) and P18(IKN4c) are tumor suppressor proteins that act in different cellular lineages and/or pathways with limited compensatory roles.  (+info)

Genome-wide miRNA expression profile has identified microRNA (miR)-96 as one of upregulated miRNAs in clinical bladder cancer (BC) tissues compared to normal bladder tissues. The aim of this study was to confirm the expression pattern of miR-96 in BC tissues and to investigate its involvement in carcinogenesis. Quantitative real-time PCR was performed to detect the expression levels of miR-96 in 60 BC and 40 normal control tissues. Bioinformatics prediction combined with luciferase reporter assay were used to verify whether the cyclin-dependent kinase inhibitor CDKN1A was a potential target gene of miR-96. Cell counting kit-8 and apoptosis assays were further performed to evaluate the effects of miR-96-CDKN1A axis on cell proliferation and apoptosis of BC cell lines. We validated that miR-96 was significantly increased in both human BC tissues and cell lines. According to the data of miRTarBase, CDKN1A might be a candidate target gene of miR-96. In addition, luciferase reporter and Western blot assays
Many cancers overexpress ATF4, a stress-induced transcription factor that promotes cell survival under hypoxic conditions and other stresses of the tumor microenvironment, but the potential contributions of ATF4 to oncogenesis itself have been little explored. Here, we report that ATF4 promotes oncogene-induced neoplastic transformation by suppressing the expression of cellular senescence-associated genes. Strikingly, primary embryo fibroblasts from ATF4-deficient mice were resistant to transformation by coexpression of H-rasV12 and SV40 large T antigen. In wild-type cells these oncogenes induced expression of the murine Atf4 gene along with the cyclin-dependent kinase inhibitor Cdkn2a, which encodes the cell senescence-associated proteins p16INK4 and p19ARF. Elevated levels of ATF4 were sufficient to suppress expression of these proteins and drive oncogenic transformation. Conversely, genetic ablation of ATF4 led to constitutive expression of p16INK4a and p19ARF, triggering cellular senescence. ...
Acts as a transcriptional activator: mediates transcriptional activation by binding to E box-containing promoter consensus core sequences 5-CANNTG-3. Associates with the p300/CBP transcription coactivator complex to stimulate transcription of the secretin gene as well as the gene encoding the cyclin-dependent kinase inhibitor CDKN1A. Contributes to the regulation of several cell differentiation pathways, like those that promote the formation of early retinal ganglion cells, inner ear sensory neurons, granule cells forming either the cerebellum or the dentate gyrus cell layer of the hippocampus, endocrine islet cells of the pancreas and enteroendocrine cells of the small intestine. Together with PAX6 or SIX3, is required for the regulation of amacrine cell fate specification. Also required for dendrite morphogenesis and maintenance in the cerebellar cortex. Associates with chromatin to enhancer regulatory elements in genes encoding key transcriptional regulators of neurogenesis.
Ten primary anaplastic meningiomas (World Health Organisation classification), taken during the course of surgical procedures, were studied. No radiotherapy had been performed before surgery.. Each sample was divided into two portions: one was processed for conventional histopathological diagnosis and the other was snap frozen in liquid nitrogen. Five micron thick cryostat sections were used for immunohistochemical staining after air drying and fixation in absolute cold acetone for 10 minutes. At least three non- consecutive sections were analysed, to evaluate the possible occurrence of false negative results.. Immunostaining was performed using the monoclonal antibody BC-1, specific for the oncofetal FN isoform according to the characterisation performed in this laboratory.1 The antihuman Ki-67 and CD-31 monoclonal antibodies, both purchased from Dako (Carpentaria, CA, USA), were also employed to detect the nuclei of proliferating cells and the vascular endothelium respectively. Double staining ...
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 ...
TY - JOUR. T1 - A Systematic Review of Ion Radiotherapy in Maintaining Local Control Regarding Atypical and Anaplastic Meningiomas. AU - Coggins, William S.. AU - Pham, Nguyen K.. AU - Nguyen, Anthony V.. AU - Branch, Daniel W.. AU - Guillet, June Y.. AU - Korst, Genevieve. AU - Lall, Rishi R.. PY - 2019/12. Y1 - 2019/12. N2 - Objective: Atypical and anaplastic meningiomas, unlike their benign counterparts, are highly aggressive, locally destructive, and likely to recur after treatment. These diseases are difficult to definitively treat with traditional radiotherapy without injuring adjacent brain parenchyma. The physical properties of ion radiotherapy allows for treatment plans that avoid damaging critical neural structures. The objectives of this systematic review were to evaluate the use and efficacy of ion radiotherapy in the treatment of atypical and anaplastic meningiomas. Methods: We performed a systematic review of the literature by querying the PubMed and Ovid databases to identify and ...
Anaplastic meningiomas (also known as malignant meningiomas) are uncommon, accounting for only ~1% of all meningiomas 1. Along with rhabdoid meningioma and papillary meningioma are considered WHO grade III tumors and demonstrate aggressive local ...
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Aim: The aim of this study was to assess both the epidermal growth factor receptor (EGFR) protein expression by immunohistochemistry and the EGFR gene amplification by fluorescence in situ hybridization in meningiomas of different grade, in order to evaluate their possible role in the development of the disease. EGFR protein belongs to the family of tyrosine kinase growth factor receptors, which also includes HER2, HER3 and HER4. Elevated expression or activity of EGFR has been reported in several cancers, including brain tumours. EGFR activation can enhance the malignant potential of epithelial tissues ...
White Ink found in: Higgins Pigment-Based Drawing Ink, Higgins Super White Pigment-Based Waterproof Drawing Ink, Handy Art Block Ink, Jacquard Screen..
Lockheed Martin unveiled the HULC system at the Association of the United States Army Winter Symposium held in Fort Lauderdale, Florida, in February 2009.. In July 2010, the company signed a $1.1m contract with the US Army Natick Soldier Center for testing and evaluating the ruggedised HULC design.. Under the contract, the Natick Soldier Center tested the HULC for its effect on the soldiers performance, the energy that a soldier spends while using it and the adaptability of the system while carrying various loads and moving at various speeds. The contract has also provided provision for field trials of the system.. The HULC underwent laboratory testing in October 2010, after Lockheed Martin upgraded the ruggedised system for flexibility and suitability to a variety of users. The system was put through biomechanical, dynamic load and environmental testing.. Treadmill testing measured the decrease in metabolic cost of the user. The systems sustainability in various environmental conditions was ...
2Hacettepe Üniversitesi Tıp Fakültesi Beyin Cerrahisi Anabilim Dalı, Ankara Meningiomas represent approximately 13-26% of primary intracranial tumours. Many small meningiomas have no symptoms during life and may be found incidentally at autopsy. Such incidental meningiomas are detected more frequently in recent years because of the advent of CT and MRI. Malignant (anaplastic) meningiomas are less common lesions, accounting for 1-2.8% of meningiomas. Recently, clear cell and chordoid meningiomas have been classified as WHO Grade II and rhabdoid and papillary meningiomas classified as WHO Grade III tumors without pathological criteria for malignancy. Here we report a rare case of rhabdoid meningioma in a 31 year-old man. Using the presented case we discuss the prognostic significance of recognition of a rhabdoid meningioma in light of the literature. Anahtar Kelimeler : Meningioma, rhabdoid meningioma, prognostic significance ...
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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Plastic disposable 3ml pipette or eye dropper. Glass pipette printed with .25, .50, .75, and 1.0ml markings. Fits a 30ml/1oz Boston round bottle or use by itself for mixing your graywashes and other inks. Comes in a pack of 4.
The PS-12 system is formulated to achieve the highest strength finished Ink blenders possible without sacrificing print quality. Paper Series can be used with our Color Matcher Ink management system to match standard and customer colors. All ink systems developed by Interactive Inks are available for use with our custom ACT Ink System® package for advanced formulation, correction and quality control ...
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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 ...
Our research line is made of three sublines, specialized in the investigation of brain pathologies, including cerebrovascular diseases, neurodegenerative diseases, and brain ageing.. ...
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Learn about the advantages that make UV-cured ink the better choice over its solvent-based partner for the majority of printing companies.
Fingerprint Dive into the research topics of The cyclin-dependent kinase inhibitor p21,sup,WAF1/Cip1,/sup, is an antiestrogen-regulated inhibitor of Cdk4 in human breast cancer cells. Together they form a unique fingerprint. ...
Linting. Removal of lint from the surface of uncoated paper is generally considered to be a paper problem, but it can often be solved by manipulating the ink. Decreasing the ink. Decreasing the ink tack and increasing the flow of dampening solution are two of the ways to reduce linting.. Trapping. Variations in trapping result in color variation in lithography. Causes of trapping problems when attempting to trap on wet ink are entirely different than those when attempting to trap on dry ink. Wet trapping is the ability of a wet ink film to accept another wet ink film printed over it, while dry trapping is the ability of a dry film to accept a wet film printed over it.. Wet trap. To assure good wet trap, two things must be kept under control: ink tack and ink film thickness. PIA/GATF has always recommended that inks vary by one or two tack units on multiunit presses. A thin ink film will not trap properly over a thick ink film, so that even if ink tack is properly controlled, ink film thickness ...
2017) Keywords: Biomarkers, Tumor Carcinoma, Squamous Cell Cell Transformation, Viral Cyclin-Dependent Kinase Inhibitor p16 DNA, Viral Humans In Situ Hybridization Neoplasm Proteins Oncogene Proteins, .... ...
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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.. ...
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|p sourcefile=api/System.Windows.Ink.StrokeCollection.IndexOf.yml sourcestartlinenumber=1 jsonPath=/members/0/summary|Returns the index of the specified |xref data-throw-if-not-resolved=true uid=System.Windows.Ink.Stroke||/xref| in the |xref data-throw-if-not-resolved=true uid=System.Windows.Ink.StrokeCollection||/xref|.|/p|
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
Pigment info: PR101Series 28oz (236ml) jar Akua Intaglio Ink was originally formulated for intaglio printmaking, however this ink can also be applied with a brayer for relief printmaking, monotype, and collagraphs;
Eco-solvent IQDEMY inks for your printing machine are an optimal choice for reaching high quality and high-speed printing. Usage of eco-solvent IQDEMY inks brings new opportunities: inks are ecologically clean and suitable for interior printing. ...
Your Search Returned No Results.. Sorry. There is currently no product that acts on isoform together.. Please try each isoform separately.. ...
An aqueous ink comprising at least one dye having at least one ionic hydrophilic group within a molecule thereof and represented by the following formula (1): ##STR00001## wherein A and B each indepen
This is a guide about removing pen ink from walls. Removing ink from walls needs to be done carefully so as not to damage the paint.
Summer is so sweet Winter is always so cold What does fall feel like? (ok teen ink said I had to enter an article at least a hundred characters long so i'm typing this to make it longer)
Highly up-regulated in liver cancer (HULC) was originally identified as the most overexpressed long non-coding RNA in hepatocellular carcinoma. Since its discovery, the aberrant up-regulation of HULC has been demonstrated in other cancer types, including gastric cancer, pancreatic cancer, osteosarcoma and hepatic metastasis of colorectal cancer. Recent discoveries have also shed new light on the upstream molecular mechanisms underlying HULC .... Read More » ...
1OIT: Imidazo[1,2-A]Pyridines: A Potent and Selective Class of Cyclin-Dependent Kinase Inhibitors Identified Through Structure-Based Hybridisation
Staedtler Lumocolor, an innovative alternative to UV-cured ink, alternatives to HP latex ink, alternatives to eco-solvent ink: why do these inks (Lumocolor, Kiian from Manoukian, and Magic Ink not get past niche market acceptance? What advantages does Sepiax inks have that may allow them to be significantly more successful?
A natural wax-containing ink jet ink for use in an ink jet apparatus which features good print quality. The ink jet ink is discharged from the ink jet ink apparatus at elevated temperatures above ambient.
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China Solvent Ink catalog of Challenger Sk4 Seiko Solvent Ink, Infiniti Sk4 Seiko Solvent Ink provided by China manufacturer - Hongkong Liyu Technology Co., Ltd., page1.
CDKN2A; ARF; CDK4I; CDKN2; CMM2; INK4; INK4A; MLM; MTS-1; MTS1; P14; P14ARF; P16; P16-INK4A; P16INK4; P16INK4A; P19; P19ARF; TP16 ...
Herein is disclosed a method for processing a liquid electrostatic ink composition, the method comprising: providing an initial liquid electrostatic ink composition comprising chargeable toner partic
•Manufacturer - DesignWorks Ink•Brand - Designworks Ink•Model number - JP752-2114•Colour - Amethyst•Material Type - Paper•Number of Items - 1•Manufacturer Part Number - JP752-2114
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Sandarintojas. Didžiausias pasirinkimas, greitas pristatymas. Didmeninė ir mažmeninė prekyba Signeda - didžiausia Baltijos šalyse žibintais prekiaujanti įmonė.
"Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". Ewing RM, Chu P, Elisma F, Li H, Taylor P, ... CDKN2C has been shown to interact with Cyclin-dependent kinase 4 and Cyclin-dependent kinase 6. GRCh38: Ensembl release 89: ... "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ... "Structure of the gene encoding the human cyclin-dependent kinase inhibitor p18 and mutational analysis in breast cancer". ...
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 ... "Entrez Gene: CDKN2D cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4)". Hirai H, Roussel MF, Kato JY, et al. ( ...
... is a family of cyclin-dependent kinase inhibitors (CKIs). The members of this family (p16INK4a, p15INK4b, p18INK4c, ... Kovalev GI, Franklin DS, Coffield VM, Xiong Y, Su L (September 2001). "An important role of CDK inhibitor p18(INK4c) in ... Ortega S, Malumbres M, Barbacid M (March 2002). "Cyclin D-dependent kinases, INK4 inhibitors and cancer". Biochimica et ... cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4))". Atlas of genetics and cytogenetics in oncology and haematology. ...
CDKN2C, INK4C, p18, p18-INK4C, cyclin-dependent kinase inhibitor 2C, cyclin dependent kinase inhibitor 2C. ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". مؤرشف من الأصل في 05 ديسمبر 2010.. الوسيط , ... CDKN2C‏ (Cyclin dependent kinase inhibitor 2C) هوَ بروتين يُشَفر بواسطة جين CDKN2C في الإنسان.[1][2][3] ... "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ...
... a member of the INK4 family of cyclin dependent kinase inhibitors. This disambiguation page lists articles associated with the ... P18 may refer to : P18 (band), a band formed with former Mano Negra members Daniel Jamet and Thomas Darnal Parallel 18, a ... a former Swedish Army armoured regiment P-18 radar p18 (protein) ...
Inactivation of cyclin D is triggered by several cyclin-dependent kinase inhibitor protein (CKIs) like the INK4 family (e.g. ... p14, p15, p16, p18). INK4 proteins are activated in response to hyperproliferative stress response that inhibits cell ... activate cyclin D gene in response to integrin. p27kip1 and p21cip1 are cyclin-dependent kinase inhibitors (CKIs) which ... Cyclins are eukaryotic proteins that form holoenzymes with cyclin-dependent protein kinases (Cdk), which they activate. The ...
... 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 ...
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 ...
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. ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... December 1994). "Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type ... "Entrez Gene: CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)". Tu Q, Hao J, Zhou X, Yan L, Dai H, Sun B, et al ... Cyclin-dependent kinase 4 inhibitor B also known as multiple tumor suppressor 2 (MTS-2) or p15INK4b is a protein that is ...
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 ...
"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/ ...
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 ...
... cyclin-dependent kinase inhibitor p16 MeSH D12.776.624.776.355.300 - cyclin-dependent kinase inhibitor p18 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 p19 MeSH D12.776.624.776.355.500 - cyclin-dependent kinase inhibitor p21 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 ...
... *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... K cyclin, C terminal. structure of a p18(ink4c)-cdk6-k-cyclin ternary complex ... 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 ...
... 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 ...
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. • ...
... p18, inhibits CDK4) (CDKN2C), transcript variant 1 as transfection-ready DNA - 10 µg - OriGene - cdna clones ... Myc-DDK-tagged ORF clone of Homo sapiens cyclin-dependent kinase inhibitor 2C ( ... home , products , origene , myc-ddk-tagged orf clone of homo sapiens cyclin-dependent kinase inhibitor 2c (p18, inhibits cdk4 ... Myc-DDK-tagged ORF clone of Homo sapiens cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) (CDKN2C), transcript variant ...
Absence of cyclin-dependent kinase inhibitor p27 or p18 increases efficiency of iPSC generation without induction of iPSC ...
Four INK4 proteins can prevent cell proliferation by specifically inhibiting cyclin D-dependent kinases. Both p18INK4c and ... Cyclin-Dependent Kinase Inhibitor p15 * Cyclin-Dependent Kinase Inhibitor p16 * Cyclin-Dependent Kinase Inhibitor p18 ... Cyclin-Dependent Kinase Inhibitor p15 * Cyclin-Dependent Kinase Inhibitor p16 * Cyclin-Dependent Kinase Inhibitor p18 ... Four INK4 proteins can prevent cell proliferation by specifically inhibiting cyclin D-dependent kinases. Both p18INK4c and ...
... p18) in cancer tissue. The cancer tissue page shows antibody staining of the protein in 20 different cancers. ... CDKN2C protein; Cyclin-dependent kinase inhibitor 2C (P18, inhibits CDK4), isoform CRA_a; cDNA FLJ33851 fis, clone CTONG2005635 ... Cyclin-dependent kinase 4 inhibitor C Q6ICV4 [Target identity:100%; Query identity:100%]. CDKN2C protein; Cyclin-dependent ... Cyclin-dependent kinase 4 inhibitor C Q6ICV4 [Target identity:100%; Query identity:100%]. CDKN2C protein; Cyclin-dependent ...
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: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". Ewing RM, Chu P, Elisma F, Li H, Taylor P, ... CDKN2C has been shown to interact with Cyclin-dependent kinase 4 and Cyclin-dependent kinase 6. GRCh38: Ensembl release 89: ... "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ... "Structure of the gene encoding the human cyclin-dependent kinase inhibitor p18 and mutational analysis in breast cancer". ...
Cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4). NM_001262. NM_078626. 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 2D (p19, inhibits CDK4). NM_001800. NM_079421. Gene Info. ...
CDKN2C, INK4C, p18, p18-INK4C, cyclin-dependent kinase inhibitor 2C, cyclin dependent kinase inhibitor 2C. ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". مؤرشف من الأصل في 05 ديسمبر 2010.. الوسيط , ... CDKN2C‏ (Cyclin dependent kinase inhibitor 2C) هوَ بروتين يُشَفر بواسطة جين CDKN2C في الإنسان.[1][2][3] ... "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ...
CDK6 inhibitor p18 , cyclin-dependent inhibitor , cyclin-dependent kinase 6 inhibitor p18 , p18-INK6 , cyclin-dependent kinase ... cyclin-dependent kinase inhibitor 2C (cdkn2c) Elisa Kit * cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) (Cdkn2c) ... cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) , cyclin-dependent kinase 4 inhibitor C , ... Cyclin-Dependent Kinase Inhibitor 2B (p15, Inhibits CDK4) ELISA Kits * Cyclin-Dependent Kinase Inhibitor 1C (p57, Kip2) ELISA ...
Cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) Assay Type: SYBR® Green Assay Design: Intron-spanning Application: ... Cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) Assay Type: Probe Assay Design: Intron-spanning Application: Gene ... Cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) Assay Type: EvaGreen Application: Gene Expression Unique Assay ID: ... Cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) Assay Type: Probe Application: Gene Expression Unique Assay ID: ...
... the INK4 inhibitors and the Cip/Kip inhibitors (31, 41). The INK4 proteins include p16INK4a, p15INK4b, p18INK4c, and p19INK4d, ... cell cycle traversal is regulated by cyclins and cyclin-dependent kinases (CDKs) that are in turn controlled by CDK inhibitors ... Regulation of Memory CD8 T-Cell Differentiation by Cyclin-Dependent Kinase Inhibitor p27Kip1. Anju Singh, Anna Jatzek, Erin ... Here, we have identified the cyclin-dependent kinase inhibitor p27Kip1 as a critical regulator of the CD8 T-cell homeostasis at ...
Cyclin dependent kinase 6 inhibitor; Elongation factor p18; Homolog of rat elongation factor p18; MCA3_HUMAN; Multisynthase ... p18 component of aminoacyl tRNA synthetase complex; p18 INK4c; p18 NK6; ARS-interacting multifunctional protein 3; p18 ... EEF1E1; eukaryotic translation elongation factor 1 epsilon 1; P18; eukaryotic translation elongation factor 1 epsilon-1; AIMP3 ... complex auxiliary component p18; Multisynthetase complex auxiliary component p18; ...
CDKN2C (untagged)-Human cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) (CDKN2C), transcript variant 1. 0. ... CDKN1A (untagged)-Human cyclin-dependent kinase inhibitor 1A (p21, Cip1) (CDKN1A), transcript variant 2. 0. ... CDK1 (untagged)-Human cyclin-dependent kinase 1 (CDK1), transcript variant 2. 0. ... CCNB1 (untagged)-Human cyclin B1 (CCNB1). 0. SC107373. NM_015391. ANAPC13. ANAPC13 (untagged)-Human anaphase promoting complex ...
... we show that menin-dependent histone methylation maintains the in vivo expression of cyclin-dependent kinase (CDK) inhibitors ... In vivo expression of CDK inhibitors, including p27 and p18, and other cell cycle regulators is disrupted in mouse islet tumors ... Increased expression of the Ink4a/Arf locus, which encodes the cyclin-dependent kinase inhibitor p16(INK4a) and tumor ... prevents adult β cell replication through derepression of the gene encoding cyclin-dependent kinase inhibitor 2a (INK4a). We ...
The expression of p18INK4 and p27kip1 cyclin-dependent kinase inhibitors is regulated differently during human B cell ... A pivotal role of cyclin D3 and cyclin-dependent kinase inhibitor p27 in the regulation of IL-2-, IL-4-, or IL-10-mediated ... Cdk2, Cdk4, Cdk6, cyclin D1, cyclin D2, cyclin D3, and cyclin E2 were investigated. Two representative samples of five are ... Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q translocations. ...
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 ...
Nakamaki T, Bartram C, Seriu T et al (1997) Molecular analysis of the cyclin-dependent kinase inhibitor genes, p15, p16, p18 ... 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 ...
... we determined changes in the expression of several cyclin-dependent protein kinase (CDK) inhibitors after siRNA-mediated Smad4 ... p18INK4c), while the expression of other CDK inhibitors was not altered (Figure 2I and Supplemental Figure 2, A-D).Thus, both ... TGF-beta-RI kinase inhibitor SD-208 reduces the development and progression of melanoma bone metastases. Cancer Res. 2011;71(1 ... Kinase switching in mesenchymal-like non-small cell lung cancer lines contributes to EGFR inhibitor resistance through pathway ...
P18 INK4c antibody LS-C208388 is an APC-conjugated rabbit polyclonal antibody to human p18 INK4c (CDKN2C). Validated for ELISA ... About CDKN2C / p18 INK4c. CDKN2C / p18 INK4c is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein ... CDKN2C Antibody, CDK6 inhibitor p18 Antibody, CDKN6 Antibody, Cyclin-dependent inhibitor Antibody, p18 INK4c Antibody, p18-INK6 ... P18 INK4c antibody LS-C208388 is an APC-conjugated rabbit polyclonal antibody to human p18 INK4c (CDKN2C). Validated for ELISA ...
Frequent inactivation of the cyclin-dependent kinase inhibitor p18 by homozygous deletion in multiple myeloma cell lines: ... Genomic alterations leading to aberrant activation of cyclin/cyclin-dependent kinase (cdk) complexes drive the pathogenesis of ... p18INK4c is a member of the INK4 family of cdk inhibitors, which includes p16INK4a, p15INK4b, p18INK4c, and p19INK4d. Members ... Cyclin-dependent kinase 6 (CDK6) amplification in human gliomas identified using two-dimensional separation of genomic DNA. ...
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. ...
Its mechanism facilitates the expression of the cyclin-dependent kinases inhibitors (CDKIs) p53, p21, p27, p16, and p18, as ... well as the non-expression of cyclin-dependent kinases (CDKs) activity. ... Furthermore, by using genechip analysis, we observed that linalool can promote p53, p21, p27, p16, and p18 gene expression. ... After treating U937 cells with linalool for 6 h, we found an increased sub-G1 peak and a dose-dependent phenomenon, whereby ...
Quantitative RT-PCR showed that silencing PANDA increased mRNA levels of the cyclin-dependent kinase inhibitor p18, which ... Inhibitors targeting AP1, MEK, Sp1 and STAT3 blunted the expression of both alkaline phosphatase and YKL-40 by MG63 cells in ... In the investigations of mechanism of action, inhibitors of apoptosis such as XIAP, BIRC5 and CLSPN showed a clear down- ... Furthermore, the low level of miR-124 was associated with increased expression of Sphingosine kinase 1 (SPHK1) in OS cells and ...
Mice lacking p53 and one or two alleles of the cyclin D-dependent kinase inhibitor p18Ink4c are prone to medulloblastoma ... The Ink4c gene, which encodes a polypeptide inhibitor (p18Ink4c) of the cyclin-dependent kinases (Cdk), Cdk4 and Cdk6, is ... 2A, left lane), the levels of expression of cyclin D2 eclipsed those of cyclin D1 in these tumor cells, whereas no tumor- ... 1E). Array CGH also revealed an amplicon on chromosome 7 that encodes cyclin D1, and FISH detected increased cyclin D1 copy ...
Quantitative RT-PCR showed that silencing PANDA increased mRNA levels of the cyclin-dependent kinase inhibitor p18, which ... In particular, IκB kinase α (IKKα), one of two catalytic subunit of IKK complex, has been described to be associated to cancer ... CONCLUSION: These results suggest that PANDA promotes G1-S transition by repressing p18 transcription, and thus promotes U2OS ... A recombinant eukaryotic plasmid heat shock protein 70-polo-like kinase 1-short hairpin RNA (pHSP70-Plk1-shRNA) under ...
Cyclin-dependent kinase 4 inhibitor C; Cyclin-dependent kinase 6 inhibitor; p18-INK6; cyclin-dependent kinase inhibitor 2C (p18 ... CDK6 inhibitor p18; cyclin-dependent inhibitor; cyclin-dependent kinase 4 inhibitor C; cyclin-dependent kinase 6 inhibitor p18 ... Cyclin-dependent kinase 4 inhibitor C; Cyclin-dependent kinase 6 inhibitor; cyclin-dependent kinase 6 inhibitor p18; cyclin- ... Cyclin-dependent kinase 4 inhibitor C; Cyclin-dependent kinase 6 inhibitor; p18-INK6; CDKN6; cyclin-dependent kinase inhibitor ...
... arrest in T.Tn cells induced by troglitazone could be correlated with an increased level of cyclin-dependent kinase inhibitor ... p27(Kip1), p21(Cip1/Waf1), and p18(Ink4c). Moreover, troglitazone treatment increased the expression of interleukin-1 alpha, a ... The growth-inhibitory effect was evidenced by a dose-dependent inhibition of deoxyribonucleic acid synthesis and was associated ...
Cheng and his team isolated p18-deficient stem cells... Stem cells have great potential but we need to develop novel strateg ... p18 is a molecule in a class of so-called "cyclin-dependent kinase inhibitors" that are critical inhibitors of cell cycle ... improved long-term engraftment of stem cells in bone marrow leading us to the conclusion that p18 is a strong inhibitor to stem ... As a result, they concluded that blocking the function of p18 may be a productive way to enhance the efficacy of stem cell ...
Georgitsi M: MEN-4 and other multiple endocrine neoplasias due to cyclin-dependent kinase inhibitors (p27(Kip1) and p18(INK4C ... Agarwal SK, Mateo CM, Marx SJ: Rare germline mutations in cyclin-dependent kinase inhibitor genes in multiple endocrine ... Functional characterization of a rare germline mutation in the gene encoding the cyclin-dependent kinase inhibitor p27Kip1 ( ... Wells SA: Advances in the management of MEN2: from improved surgical and medical treatment to novel kinase inhibitors. Endocr ...
Nakayama, K. (1998). Cip/Kip cyclin-dependent kinase inhibitors: brakes of the cell cycle engine during development. BioEssays ... p18Ink4c and p19Ink4d; and the Cip/Kip family, comprising p21Cip1, p27Kip1 (hereafter referred to as Kip1; Cdkn1b - Mouse ... Assembly of cyclin D-dependent kinase and titration of p27Kip1 regulated by mitogen-activated protein kinase kinase (MEK1). ... Cunningham, J. J. and Roussel, M. F. (2001). Cyclin-dependent kinase inhibitors in the development of the central nervous ...
  • In mammalian cells, cell cycle traversal is regulated by cyclins and cyclin-dependent kinases (CDKs) that are in turn controlled by CDK inhibitors (CKIs) ( 31 ). (asm.org)
  • The activating cyclins for these CDKs, cyclins D1 and E, are present in senescent cells at similar or elevated levels relative to early passage cells ( 8 ). (pnas.org)
  • In the case of glioblastoma multiforme (GBM), these alterations are most commonly due to homozygous deletion of p16 INK4a and less commonly due to genomic amplifications of individual genes encoding cyclins or cdks. (aacrjournals.org)
  • Another 5% to 10% of GBMs have amplifications of individual cyclins and cdks, including cdk4, cdk6, and cyclin D1 ( 5 - 7 ). (aacrjournals.org)
  • Its mechanism facilitates the expression of the cyclin-dependent kinases inhibitors (CDKIs) p 53 , p21 , p27 , p16 , and p18 , as well as the non-expression of cyclin-dependent kinases (CDKs) activity. (mdpi.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)
  • 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)
  • 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)
  • Cell cycle progression is controlled in part by a family of cyclin proteins and cyclin dependent kinases (Cdks). (scbt.com)
  • 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)
  • One contributing factor may be the sequestration of cyclins A, E, D1, and D3, as well as their cdk partners (cdks 1,2, 4 and 6), in the cytoplasm in quiescent adult human β-cells ( 9 - 12 ). (diabetesjournals.org)
  • Forced overexpression of cyclins/cdks permits induction of cell cycle entry associated with nuclear translocation of cyclins and cdks, suggesting that trafficking and proliferative events are linked ( 9 - 12 ). (diabetesjournals.org)
  • Therefore, identification of any factor or signal in human β-cells to increase cyclins/cdks and their nuclear trafficking may provide a useful hint to promote human β-cell proliferation and expansion for diabetes therapy. (diabetesjournals.org)
  • 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)
  • Cyclin-dependent kinases (CDKs) are protein kinases characterized by needing a separate subunit - a cyclin - that provides domains essential for enzymatic activity. (biomedcentral.com)
  • Unlike the prototypical Cdc28 kinase of budding yeast, most of these CDKs bind one or a few cyclins, consistent with functional specialization during evolution. (biomedcentral.com)
  • Cyclin-dependent kinases (CDKs) are serine/threonine kinases whose activity depends on a regulatory subunit - a cyclin. (biomedcentral.com)
  • Based on the sequence of the kinase domain, CDKs belong to the CMGC group of kinases (named for the initials of some members), along with mitogen-activated protein kinases (MAPKs), glycogen synthase kinase-3 beta (Gsk3β), members of the dual-specificity tyrosine-regulated kinase (DYRK) family and CDK-like kinases [ 1 ]. (biomedcentral.com)
  • In related kinases such as MAPKs, substrate specificity is conferred by docking sites separated from the catalytic site, whereas CDKs are characterized by dependency on separate protein subunits that provide additional sequences required for enzymatic activity. (biomedcentral.com)
  • Since these pioneer studies conducted in the 1980s, the importance of CDKs acting as a major eukaryotic protein kinase family involved in the integration of extracellular and intracellular signals to modulate gene transcription and cell division has been clearly established [ 3 - 6 ]. (biomedcentral.com)
  • These CDKs can be grouped as, first, CDKs that bind multiple cyclins and can regulate the cell cycle and, second, CDKs that are activated by a single cyclin and are involved in the regulation of transcription. (biomedcentral.com)
  • The second group comprises four CDKs - Kin28, Srb10, Bur1 and Ctk1 - each activated by a single specific cyclin (Figure 1 ). (biomedcentral.com)
  • These cyclins are usually not regulated in a cell-cycle-dependent manner, and the members of this second group of CDKs are involved in the control of gene transcription. (biomedcentral.com)
  • Cells of the budding yeast Saccharomyces cerevisiae contain two cell-cycle-related CDKs that are activated by multiple cyclins - Cdc28 and Pho85. (biomedcentral.com)
  • Also indicated is the cyclin partner for the mammalian CDKs. (biomedcentral.com)
  • Fungi contain 6 to 8 CDKs and 9 to 15 cyclins, whereas flies and echinodermata contain 11 CDKs and 14 cyclins, and human cells have 20 CDKs and 29 cyclins (Box 1) [ 7 ]. (biomedcentral.com)
  • The INK4 proteins include p16 INK4a , p15 INK4b , p18 INK4c , and p19 INK4d , which are specific inhibitors of CDK4 and CDK6 ( 3 ). (asm.org)
  • The Ink4c gene, which encodes a polypeptide inhibitor (p18 Ink4c ) of the cyclin-dependent kinases (Cdk), Cdk4 and Cdk6, is induced transiently in CGNPs before their exit from the cell cycle ( 13 ), but the protein persists throughout subsequent phases of cerebellar patterning. (aacrjournals.org)
  • To determine a possible mechanism by which senescent human fibroblasts maintain a hypophosphorylated Rb, we examined the expression levels and interaction of the Rb kinases, CDK4 and CDK6, and the cyclin-dependent kinase inhibitors p21 and p16 in senescent HDFs. (pnas.org)
  • Immunodepletion analysis of p21 and p16 from the senescent cell extracts revealed that p16 is the major CDK inhibitor for both CDK4 and CDK6 kinases. (pnas.org)
  • Immunoprecipitation of CDK4 and CDK6 and their associated proteins from radiolabeled extracts from senescent HDFs showed no other CDK inhibitors. (pnas.org)
  • Three cyclin-dependent kinases, CDK2, CDK4, and CDK6, are involved in the phosphorylation of the Rb protein (reviewed in ref. 5 ). (pnas.org)
  • RT "Preferences for phosphorylation sites in the retinoblastoma protein RT of D-type cyclin-dependent kinases, Cdk4 and Cdk6, in vitro. (genome.jp)
  • NSCLCs frequently overexpress cyclin D1 (4 , 5 , 6 , 7) , leading to increased activity of cdk4 and cdk6 and loss of growth control. (aacrjournals.org)
  • The p16 family (p15, p16, p18 and p19) binds to and inhibits the activities of CDK4 and CDK6. (biomedcentral.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)
  • p16 INK4a is a cyclin-dependent kinase (CDK) inhibitor, and binds CDK4 and CDK6 and inhibits their kinase activity. (takarabio.com)
  • Prolonged exposure to high glucose with or without insulin downregulated B cell lymphoma 2-associated X (Bax) and failed to enhance the expression of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) in drug-treated cells. (hindawi.com)
  • 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)
  • MEF2D (myocyte enhancer factor 2D) is a transcription factor downstream of the p38 MAPK (mitogen-activated protein kinase) that also directs ASH2L-containing complexes to MyoD (myoblast determination protein)-bound genes in myoblasts [66]. (doctorabel.us)
  • Four INK4 proteins can prevent cell proliferation by specifically inhibiting cyclin D-dependent kinases. (nih.gov)
  • Seven cyclin-dependent kinase inhibitor proteins have thus far been identified. (wikipedia.org)
  • The p21 family currently includes two related proteins, p27 Kip1 and p57 Kip2 , and the p16 family currently includes four related proteins: p16 INK4a (also variously known as MTS1, CDK4I and CDKN2), p15 INK4b (also known as MTS2), p18 INK4c , and p19 INK4d (reviewed in ref. 10 ). (pnas.org)
  • The action of the INK4 and CIP/KIP families of cell cycle inhibitors on Cdk4/6- or Cdk2-containing complexes, respectively, is thought to lead ultimately to inhibition of phosphorylation of the retinoblastoma protein, Rb, and the related p107 and p130 proteins. (pnas.org)
  • 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)
  • In addition, two groups of inhibitors, known as Cip/Kip and INK4 proteins, also regulate cdk activity. (aacrjournals.org)
  • CCND1 gene is alternatively spliced to produce two cyclin D1 mRNA isoforms which are translated in two proteins: cyclin D1a and cyclin D1b. (biomedcentral.com)
  • The two corresponding proteins cyclin D1a and D1b differ only in the last 55 amino acids of the carboxy-terminus. (biomedcentral.com)
  • Cdk proteins work in concert with the cyclins to phosphorylate key substrates involved in each phase of cell cycle progression. (scbt.com)
  • Another family of proteins, Cdk inhibitors, also plays a role in regulating the cell cycle by binding to cyclin-Cdk complexes and modulating their activity. (scbt.com)
  • 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)
  • 1996). Wnt inhibitor factor (WIF) proteins, due to their similarity to the extracellular domain of derailed/RYK Wnt transmembrane receptors, can also regulate Wnt signaling by interacting with Wnt ligands (Hsieh et al. (pharmaceuticalintelligence.com)
  • 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)
  • Cell-cycle arrest in T.Tn cells induced by troglitazone could be correlated with an increased level of cyclin-dependent kinase inhibitor p27(Kip1), p21(Cip1/Waf1), and p18(Ink4c). (nih.gov)
  • Recently, several negative regulators of the cell cycle, such as the cyclin-dependent kinase inhibitors p21 Cip1 , p27 Kip1 , and p16 INK4a /p19 ARF , have been demonstrated to have a role in regulating HSC fate decisions, suggesting that regulation of the G 1 -S phase transition can contribute to HSC self-renewal. (pnas.org)
  • Blockage of K + channels and membrane depolarization also caused accumulation of the cyclin-dependent kinase inhibitors p27 Kip1 and p21 CIP1 in OP cells. (jneurosci.org)
  • To begin to identify cell cycle and cell death regulatory factors involved in antioxidant-induced growth arrest and PCD, we have studied colorectal carcinoma cells (CRCs) that differ in expression of the tumor suppressor protein p53, and of the cyclin-dependent kinase (CDK) inhibitor p21(Waf1/Cip1). (nih.gov)
  • Growth arrest was not associated with upregulation of the CDK inhibitors p21(Waf1/Cip1), p18(ink4c) or p16(ink4a), but was associated with a decrease in reactive oxygen species (ROS). (nih.gov)
  • 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)
  • 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)
  • The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. (wikipedia.org)
  • There are two classes of CKI: the INK4 inhibitors and the Cip/Kip inhibitors ( 31 , 41 ). (asm.org)
  • These studies have predominantly focused on inhibitors of G 1 -S phase cell cycle progression, in particular the CIP/KIP and INK4 family of cyclin-dependent kinase inhibitors, and they have revealed that the loss of these genes can alter HSC self-renewal and differentiation. (pnas.org)
  • CDKN2C / p18 INK4c is a member of the INK4 family of cyclin-dependent kinase inhibitors. (lsbio.com)
  • A gene on chromosome 1p32 that encodes a member of the INK4 family of cyclin-dependent kinase inhibitors, which form a complex with CDK6 and to a lesser extent with CDK4, preventing activation of CDK kinases and thus acting as cell growth regulators by controlling cell cycle progression through G1. (thefreedictionary.com)
  • An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN-LIKE REPEATS. (bvsalud.org)
  • This process is in part regulated by a family of Cdk inhibitors (CKIs) called the Ink4 family (Inhibitors of Cdk4). (diva-portal.org)
  • 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 C is an enzyme that in humans is encoded by the CDKN2C gene. (wikipedia.org)
  • CDKN2C has been shown to interact with Cyclin-dependent kinase 4 and Cyclin-dependent kinase 6. (wikipedia.org)
  • CDKN2C ‏ ( Cyclin dependent kinase inhibitor 2C ) هوَ بروتين يُشَفر بواسطة جين CDKN2C في الإنسان . (wikipedia.org)
  • On www.antibodies-online.com are 6 Cyclin-Dependent Kinase Inhibitor 2C (p18, Inhibits CDK4) (CDKN2C) ELISA Kits from 5 different suppliers available. (antibodies-online.com)
  • Data suggest that cell cycle-dependent kinase inhibitors CDKN2C/p18 and CDKN1A/p21 (show CDKN1A ELISA Kits ) facilitate cell cycle entry/cell proliferation of quiescent adult human pancreatic beta cells in primary culture (from tissues obtained from organ donors). (antibodies-online.com)
  • Antigen standard for cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) (CDKN2C), transcript variant 1 is a lysate prepared from HEK293T cells transiently transfected with a TrueORF gene-carrying pCMV plasmid and then lysed in RIPA Buffer. (creativebiomart.net)
  • P18 INK4c antibody LS-C208388 is an APC-conjugated rabbit polyclonal antibody to human p18 INK4c (CDKN2C). (lsbio.com)
  • For instance, mutations in the HRAS [3] (v-Ha-ras Harvey rat sarcoma viral oncogene homolog) gene and structural rearrangements affecting the CDKN2C [cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)] gene were identified in the melanoma patient of the aforementioned study. (thefreedictionary.com)
  • Here, we have identified the cyclin-dependent kinase inhibitor p27 Kip1 as a critical regulator of the CD8 T-cell homeostasis at all phases of the T-cell response to an acute viral infection in mice. (asm.org)
  • 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)
  • 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)
  • PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27 Kip1. (univ-paris5.fr)
  • p27(Kip1) controls cytokinesis via the regulation of citron kinase activation. (univ-paris5.fr)
  • 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)
  • Deletions of p18 INK4c often occurred in tumors also harboring homozygous deletions of p16 INK4a . (aacrjournals.org)
  • In contrast to loss of p18 INK4c , loss of both p16 INK4a and p19 INK4d had little effect on HSC function, with only a subtle increase in serial repopulation reported ( 5 ). (pnas.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)
  • All such tumors exhibited complete loss of function of the Patched 1 ( Ptc1 ) gene encoding the receptor for sonic hedgehog, and many exhibited other recurrent genetic alterations, including trisomy of chromosome 6, amplification of N- Myc , modest increases in copy number of the Ccnd1 gene encoding cyclin D1, and other complex chromosomal rearrangements. (aacrjournals.org)
  • These studies identify p18 INK4c as a GBM tumor suppressor gene, revealing an additional mechanism leading to aberrant activation of cyclin/cdk complexes in this terrible malignancy. (aacrjournals.org)
  • They found that blood stem cells from mice missing a gene called p18 were much better able to multiply and grow. (bio-medicine.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)
  • A mutated MEN1 gene therefore leads to a decrease in p18 and p27 expression, which accelerates cell-cycle progression. (doctorabel.us)
  • 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)
  • The human cyclin-dependent kinase inhibitor 2A (CDKN2A) gene generates several transcript variants that differ in their first exons. (takarabio.com)
  • 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)
  • 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)
  • Rb inactivation leads to expression of E2F-dependent genes such as thymidine kinase, DNA polymerase-α, cdc2, and cyclin A ( 5 ), which are not expressed in senescent cells ( 6 ), indicating that the failure to phosphorylate Rb is important in the growth arrest of senescent cells. (pnas.org)
  • Importantly, cyclin K and cyclin D1b have no major action on cell cycle or apoptosis regulatory genes. (biomedcentral.com)
  • Various cardiac development related genes involving the cell cycle (cyclin B1, proliferating cell nuclear antigen (PCNA), and Ki67), growth factors (IGF-II, pleiotrophin (PTN), and midkine (MK)), and transcriptional regulation, cytoskeleton, and detoxification enzymes were identified by microarray analysis. (pubmedcentralcanada.ca)
  • This protein has been shown to interact 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)
  • Analysis of B1a lymphocyte phenotypes of p18 -deficient C57BL/6 mice finds that p18 is a key regulator of the size of the B1a cell pool. (antibodies-online.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)
  • These cyclin-CDK complexes, as well as cyclin E-CDK2 complexes later in the cell cycle, phosphorylate retinoblastoma protein (Rb). (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)
  • 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)
  • Prolonged exposure to high glucose and insulin enhanced cyclin D, cyclin-dependent kinase 4 (Cdk4), and Cdk2 expression and suppressed cyclin-dependent kinase inhibitors p21 and p15/16 in HBlEpC cotreated with pioglitazone and metformin. (hindawi.com)
  • 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)
  • To test the tumorigenic potential of cyclin D1b in vivo , we generated cell clones derived from the non- CCND1 expressing MM LP-1 cell line, synthesizing either cyclin D1b or cyclin K, a structural homolog and viral oncogenic form of cyclin D1a. (biomedcentral.com)
  • Among the five NPC-PDXs, three had cyclin D1 (CCND1) amplification while four had cyclin-dependent kinase inhibitor CDKN2A deletion. (springernature.com)
  • CNV analysis disclosed that plasma CCND1/CDKN2A ratio is correlated with EBV DNA load in NPC patients' plasma and could serve as a screening test to select potential CDK4/6 inhibitor treatment candidates. (springernature.com)
  • Genomic alterations leading to aberrant activation of cyclin/cyclin-dependent kinase (cdk) complexes drive the pathogenesis of many common human tumor types. (aacrjournals.org)
  • Additionally, activation of the phosphatidylinositol-3-OH kinase signaling pathway via mutational inactivation of the PTEN tumor suppressor or mutational activation of the PIK3CA oncogene is also very common in GBM ( 2 , 3 ). (aacrjournals.org)
  • 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)
  • Favorable results with palbociclib and its recent U.S. Food and Drug Administration approval demonstrate that CDK inhibitors with narrow selectivity profiles can have clinical utility for therapy based on individual tumor genetics. (aspetjournals.org)
  • Based on our NPC PDX model and RNA sequencing, Palbociclib, a cyclin-dependent kinase inhibitor, proved to have anti-tumor effects by inducing G1 arrest. (springernature.com)
  • CONCLUSIONS: Our integrated information of sequencing-based genomic studies and tumor transcriptomes with drug treatment in NPC-PDX models provided guidelines for personalized precision treatments and revealed a cyclin-dependent kinase inhibitor Palbociclib as a novel candidate drug for NPC. (springernature.com)
  • A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. (harvard.edu)
  • Extracellular-Regulated Protein Kinase 5-Mediated Control of p21 Expression Promotes Macrophage Proliferation Associated with Tumor Growth and Metastasis. (harvard.edu)
  • The crucial role of DNA-dependent protein kinase and myelin transcription factor 1-like protein in the miR-141 tumor suppressor network. (harvard.edu)
  • These data, revealed in the absence of p53, suggest a cell-type specific tumor suppressing role for p18 Ink4c . (diva-portal.org)
  • 11 Several factors including cell cycle regulators (cyclins, cyclin dependent kinases, and proliferating cell nuclear antigen) and oncogenes (c-myc and Rb) are reportedly involved in cardiac muscle cell cycle progression. (pubmedcentralcanada.ca)
  • Cyclins function as regulators of cyclin-dependent kinases. (wikidoc.org)
  • In addition, these studies showed that the catalytic subunit, the CDK, must associate with a regulatory subunit, the cyclin, whose protein levels are subject to regulation during the cell cycle (this oscillation lent these regulators their cyclin name). (biomedcentral.com)
  • Cell cycle progression is delayed or stopped by cyclin-dependent kinase inhibitors, abbreviated CDIs, CKIs or CDKIs. (wikipedia.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)
  • CKIs act as brakes for the cell cycle, restraining the activity of cyclin-CDK complexes to maintain cells in the quiescent G 0 /G 1 phase or to induce cell cycle exit in proliferating cells. (asm.org)
  • Taken together, our study suggests that EGCG causes an induction of G1-phase ckis, which inhibit the cyclin-cdk complexes operative in G0/G1 phase of the cell cycle thereby causing a G0/G1-phase arrest of the cell cycle, which is an irreversible process ultimately resulting in an apoptotic cell death. (dr-rath-foundation.org)
  • Another level of regulation is their association with inhibitory partners called CKIs (Cyclin-dependent Kinase Inhibitor). (frontiersin.org)
  • This article will review the Wnt signaling pathway, preclinical data on OMP-54F28 and other Wnt pathway inhibitors and ongoing clinical trials. (pharmaceuticalintelligence.com)
  • 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)
  • The most spectacular example is a combination of PPARγ ligands with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). (eurekaselect.com)
  • The irreversible G 1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G 1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). (asm.org)
  • 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)
  • The PEST sequence which controls protein turn-over and the threonine 286 (Thr286), the site of phosphorylation by glycogen synthase kinase-3β which promotes the nuclear export of cyclin D1 and its degradation through the proteasome pathway [ 2 , 3 ], are present only in cyclin D1a. (biomedcentral.com)
  • With Wnt signaling "off," AXIN facilitates the phosphorylation of β-catenin by casein kinase 1 (CK1) and glycogen synthase kinase 3 (GSK-3 [Peifer et al. (pharmaceuticalintelligence.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)
  • The growth-inhibitory effect was evidenced by a dose-dependent inhibition of deoxyribonucleic acid synthesis and was associated with altered cell-cycle progression manifesting G1 arrest. (nih.gov)
  • Lentiviral reconstitution of p18 INK4c expression at physiologic levels in p18 INK4c -deficient but not p18 INK4c -proficient GBM cells led to senescence-like G 1 cell cycle arrest. (aacrjournals.org)
  • are not involved in ion channel-dependent cell cycle arrest in OP cells. (jneurosci.org)
  • 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)
  • A receptor-specific function for Notch2 in mediating vascular smooth muscle cell growth arrest through cyclin-dependent kinase inhibitor 1B. (univ-paris5.fr)
  • 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)
  • Cyclin D1 is a key actor for the development and progression of various cancers including hematological malignancies. (biomedcentral.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)
  • 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)
  • RT "Cyclin-dependent kinase 6 inhibits proliferation of human mammary RT epithelial cells. (genome.jp)
  • 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)
  • Interestingly, cyclin D2-in contrast to its abundance and essential presence for rodent β-cell proliferation ( 13 - 15 )-is either absent or present at very low levels in human β-cells ( 16 - 19 ). (diabetesjournals.org)
  • Surprisingly, precancerous B cells and lymphomas from Eµ- Myc mice exhibited elevated levels of p18 Ink4c mRNA and protein despite high rates of proliferation. (diva-portal.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)
  • Membrane potential-dependent transport of essential metabolic substrates during the cell cycle and/or volume regulation could also play a role (for review, see Wonderlin and Strobl, 1996 ). (jneurosci.org)
  • Mice lacking p53 and one or two alleles of the cyclin D-dependent kinase inhibitor p18 Ink4c are prone to medulloblastoma development. (aacrjournals.org)
  • The enforced expression of N-Myc or cyclin D1 in primary cerebellar granule neuron precursors isolated from Ink4c −/− , p53 −/− mice enabled the cells to initiate medulloblastomas when injected back into the brains of immunocompromised recipient animals. (aacrjournals.org)
  • In the study, Dr. Cheng and his team isolated p18-deficient stem cells from mice and found that these cells were much more efficient at repopulating injured bone marrow tissue. (bio-medicine.org)
  • In mammalian cells, two distinct families of CDK inhibitors have been characterized, represented by two prototype CDK inhibitors, p21 and p16. (pnas.org)
  • Antigen receptor signaling or exposure to growth factors triggers de novo synthesis of D-type cyclins, which then associate with their catalytic partners CDK4 or CDK6. (asm.org)
  • In the former case, cyclin T-CDK9 and cyclin C-CDK8 are only involved in transcriptional regulation, whereas cyclin H-CDK7 is involved in regulation of both the cell cycle and transcription. (springer.com)
  • Genome-wide analysis of LP-1-derived cells indicated that several cellular processes were altered by cyclin D1b and/or cyclin K expression such as cell metabolism, signal transduction, regulation of transcription and translation. (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)
  • To determine why, we explored the human PRL-prolactin receptor (hPRLR)-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5)-cyclin-cdk signaling cascade in human β-cells. (diabetesjournals.org)
  • MENIN induces the transcription of cyclin-dependent kinase inhibitors p18 and p27 [74]. (doctorabel.us)
  • 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)
  • Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. (curehunter.com)
  • Both isoforms possess the N-terminal domain, necessary for retinoblastoma protein (pRb) binding, the cyclin box, required for cyclin-dependent kinase (CDK) binding and activation and the central region, implicated in transcriptional regulation. (biomedcentral.com)
  • 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)
  • One of these, cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) or p16INK4a, interacts with, and sequesters, the E3 ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. (takarabio.com)
  • Surprisingly, mouse (but not human) Stat5a overexpression led to upregulation of cyclins D1-3 and cdk4, as well as their nuclear translocation, all of which are associated with β-cell cycle entry. (diabetesjournals.org)
  • Although the reasons for this difference are unknown, overexpression of cyclin D2 can induce human β-cell cycle entry ( 17 ). (diabetesjournals.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)
  • 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)
  • It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18. (curehunter.com)
  • RT "Transforming activity of Fbxo7 is mediated specifically through RT regulation of cyclin D/cdk6. (genome.jp)
  • These inhibitors bind to both free and complexed Cdk6, and they inhibit the activity of the cyclin D-bound Cdk6. (scbt.com)
  • 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)
  • In order to study the oncogenic potential of cyclins D1b and K in the context of mature B cells, we generated several cell clones derived from LP-1 MM cell line, expressing either cyclin D1b, Myc or cyclin K oncogenes. (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)
  • These observations have prompted great interest in the development of pharmacological cdk inhibitors that could produce similar antitumor effects. (aacrjournals.org)
  • Finally, virtually all GBMs harbor genomic alterations that lead to the constitutive activation of cyclin-dependent kinases (cdk). (aacrjournals.org)
  • Using this approach, we have identified inactivation of the p18 INK4c cdk inhibitor as an additional genomic alteration that drives the pathogenesis of GBM. (aacrjournals.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)
  • The differences in p18(INK4c )and p57(Kip2 (show CDKN1C ELISA Kits ))activities in chronic myeloid leukemia (show BCL11A ELISA Kits ) and normal stem cells suggest a different cell cycle regulation. (antibodies-online.com)
  • SGK1-Sensitive Regulation of Cyclin-Dependent Kinase Inhibitor 1B (p27) in Cardiomyocyte Hypertrophy. (univ-paris5.fr)