Cyclin-Dependent Kinase Inhibitor p27
A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
Cyclin-Dependent Kinase Inhibitor p21
Cell Cycle Proteins
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.
Cyclin-Dependent Kinase Inhibitor p16
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.
Tumor Suppressor Proteins
Cyclin-Dependent Kinase 2
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Cyclin-Dependent Kinase 4
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.
Cyclin-Dependent Kinase Inhibitor p57
Cell Line, Tumor
A cell line derived from cultured tumor cells.
Protein Kinase Inhibitors
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.
Cyclin-Dependent Kinase 5
CDC2 Protein Kinase
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.
Cyclin-Dependent Kinase Inhibitor Proteins
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
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
Cyclin-Dependent Kinase Inhibitor p18
Tumor Suppressor Protein p53
Tumor Cells, Cultured
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.
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.
E2F1 Transcription Factor
A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.
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.
Transcription Factor DP1
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.
Proliferating Cell Nuclear Antigen
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.
Cyclin-Dependent Kinase Inhibitor p15
MAP Kinase Signaling System
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.
E2F Transcription Factors
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.
Molecular Sequence Data
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.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Calcium-Calmodulin-Dependent Protein Kinases
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)
Cyclin-Dependent Kinase Inhibitor p19
S-Phase Kinase-Associated Proteins
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.
Gene Expression Regulation
Protein Kinase C
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.
Reverse Transcriptase Polymerase Chain Reaction
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.
Intracellular Signaling Peptides and Proteins
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.
Amino Acid Sequence
p38 Mitogen-Activated Protein Kinases
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.
Mitogen-Activated Protein Kinases
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).
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase Kinases
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.
Promoter Regions, Genetic
RNA, Small Interfering
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.
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.
Cyclic AMP-Dependent Protein Kinases
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.
Gene Expression Regulation, Neoplastic
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)
Mitogen-Activated Protein Kinase 3
Proto-Oncogene Proteins c-akt
Recombinant Fusion Proteins
JNK Mitogen-Activated Protein Kinases
Dose-Response Relationship, Drug
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)
Upregulation of microRNA-96 and its oncogenic functions by targeting CDKN1A in bladder cancer | Cancer Cell International |...
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. ...
Neurod1 - Neurogenic differentiation factor 1 - Mus musculus (Mouse) - Neurod1 gene & protein
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.
Accumulation of oncofetal fibronectin in the vessels of anaplastic meningiomas | Journal of Neurology, Neurosurgery & Psychiatry
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 ...
INK RECIPE SUPERTHREAD - Third Rail - 12ozProphet
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 ...
A Systematic Review of Ion Radiotherapy in Maintaining Local Control Regarding Atypical and Anaplastic Meningiomas<...
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 meningioma | Radiology Reference Article | Radiopaedia.org
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 ...
cattattoo #crazycatlady #catofinstagram #ink #inked #inkart #tattooart #tattoolife #tattoolove #tattoopassion ...
#cattattoo #crazycatlady #catofinstagram #ink #inked #inkart #tattooart #tattoolife #tattoolove #tattoopassion #tattooinspiration #tattocommunity #lamoglietatuata #thetattooedwife
Prognostic value of EGFR expression in de novo and progressed atypical and anaplastic meningiomas: an immunohistochemical and...
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 - United Art & Education
White Ink found in: Higgins Pigment-Based Drawing Ink, Higgins Super White Pigment-Based Waterproof Drawing Ink, Handy Art Block Ink, Jacquard Screen..
Human Universal Load Carrier (HULC) - Army Technology
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 ...
Türk Nöroşirürji Dergisi
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 ...
PPT - Forensic Analysis of Pens & Inks PowerPoint Presentation - ID:2249543
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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Central Ink Corp. is the premier American owned & operated Ink Manufacturer that has been producing high quality low-cost inks & services for over 80 years.
Flintlockjaw: Captain Absolute - inks!
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 ...
PCAF REGULATES THE STABILITY OF THE TRANSCRIPTIONAL REGULATOR AND CYCLIN-DEPENDENT KINASE INHIBITOR P27 KIP1. | Institute of...
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.
The cyclin-dependent kinase inhibitor p21|sup|WAF1/Cip1|/sup| is an antiestrogen-regulated inhibitor of Cdk4 in human breast...
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. ...
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How to Remove Ink From Printed Cards | eHow
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.. ...
StrokeCollection.IndexOf(Stroke) Method (System.Windows.Ink) | Microsoft Docs
|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|
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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;
Solvent & Eco-solvent inks
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. ...
Why Can Pencil Be Easily Erased Off A Paper, But Ink Cant? » Science ABC
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
CDK Inhibitors | MedChemExpress
Your Search Returned No Results.. Sorry. There is currently no product that acts on isoform together.. Please try each isoform separately.. ...
US Patent # 7,083,670. Aqueous ink and inkjet recording ink - Patents.com
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
Removing Pen Ink from Walls | ThriftyFun
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.
Seasons | Teen Ink
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)
HULC | lncRNA Blog
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 » ...
Structure Cluster - 1OIT: Imidazopyridines: a potent and selective class of Cyclin-dependent Kinase inhibitors...
1OIT: Imidazo[1,2-A]Pyridines: A Potent and Selective Class of Cyclin-Dependent Kinase Inhibitors Identified Through Structure-Based Hybridisation
Staedtler Lumocolor ink: alternatives to UV-cured ink, alternatives to HP latex ink, alternatives to solvent ink and VOCs
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?
Natural wax-containing ink jet inks - Patent # 4390369 - PatentGenius
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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الگو:PBB/1029 - ویکیپدیا، دانشنامهٔ آزاد
CDKN2A; ARF; CDK4I; CDKN2; CMM2; INK4; INK4A; MLM; MTS-1; MTS1; P14; P14ARF; P16; P16-INK4A; P16INK4; P16INK4A; P19; P19ARF; TP16 ...
US Patent # 9,709,913. Concentrating an ink composition - Patents.com
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
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Sandarintojas. Didžiausias pasirinkimas, greitas pristatymas. Didmeninė ir mažmeninė prekyba Signeda - didžiausia Baltijos šalyse žibintais prekiaujanti įmonė.
CDKN2C - ويكيبيديا
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. ... "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ...
Cyclin-dependent kinase 8
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 ...
Cyclin-dependent kinase 4
"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. Cyclin-dependent kinase 4 has been shown to interact ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ...
細胞週期 - 维基百科，自由的百科全书
CDK抑制因子（英语：Cyclin-dependent kinase inhibitor protein）. *INK4a/ARF（p14arf/p16、p15、p18、p19） ... Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle. BioEssays. June 1995, 17 (6): 471-80. PMID ... 細胞週期的進行是由不同的週期素(Cyclin)所調控。週期素意味著這些蛋白質的表現量會隨著細胞週期的進行而有所變化，進而確認週期素原來是扮演細胞
... *Cyclin-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 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 ...
ಅಪೊಪ್ಟೋಸಿಸ್ - ವಿಕಿಪೀಡಿಯ
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. • ...
Myc-DDK-tagged ORF clone of Homo sapiens cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) (CDKN2C), transcript variant...
... 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 ...
Copy number variation and selection during reprogramming to pluripotency | Nature
Expression of CDKN2C in cancer - Summary - The Human Protein Atlas
... 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 ...
GO Gene List
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 - ويكيبيديا
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. ... "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ...
Cyclin-Dependent Kinase Inhibitor 2C (p18, Inhibits CDK4) (CDKN2C) ELISA Kits</span>
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 ...
Cdkn2c - PrimePCR Assay and Template | Life Science | Bio-Rad
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: ...
OriGene -Protein Listing By Pathway/Family
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 ...
eef1e1 Protein, eukaryotic translation elongation factor 1 epsilon 1 - Creative BioMart
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; ...
Seung K. Kim M.D., Ph.D. | Stanford Medicine Profiles
... 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 ...
A p53 Defect Sensitizes Various Stages of B Cell Development to Lymphomagenesis in Mice Carrying an IgH 3′ Regulatory Region...
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. ...
Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2′-deoxycytidine ...
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 ...
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. ...
Myelodysplastic syndromes: molecular pathogenesis and genomic changes | SpringerLink
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 ...
Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in...
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. ...
Osteosarcoma | Cancer Genetics Web
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 ...
Genetic Alterations in Mouse Medulloblastomas and Generation of Tumors De novo from Primary Cerebellar Granule Neuron...
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 ...
Bone Cancers | CancerIndex
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 ...
CDKN2C - Search Results - MyBioSource
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 ...
Growth inhibition of esophageal squamous carcinoma cells by peroxisome proliferator-activated receptor-gamma ligands. - PubMed...
... 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 ...
Molecular mechanism found that may improve ability of stem cells to fig...( PITTSBURGH May 3 Adult stem cell tran...)
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 ...
Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®): Genetics - Health Professional Information [NCI] - WellSpan Health...
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 ...
IJMS | Free Full-Text | Linalool Induces Cell Cycle Arrest and Apoptosis in Leukemia Cells and Cervical Cancer Cells through...
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 ...
JCI - SMAD signaling promotes melanoma metastasis independently of phenotype switching
... 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 ...
Recombinant Human CDKN2C 293 Cell Lysate CDKN2C-7612HCL - Creative BioMart
... cyclin-dependent kinase 4 inhibitor C; INK4C; p18; p18-INK6; CDK6 inhibitor p18; cyclin-dependent inhibitor; cyclin-dependent ... Antigen standard for cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) (CDKN2C), transcript variant 1 is a lysate ... CDKN2C; cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4); ... Cyclin D associated events in G1, organism-specific biosystem; E2F transcription factor network, organism-specific biosystem; ...
CDKN2C / p18 INK4c Antibody (aa113-139, APC) for IHC, WB/Western, ELISA LS-C208388
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 ...
In vitro drug resistance and prognostic impact of p16INK4A/P15INK4B deletions in childhood T-cell acute lymphoblastic leukaemia...
Analysis of a family of cyclin-dependent kinase inhibitors: p15/MTS2/INK4B, p16/MTS1/INK4A, and p18 genes in acute ... p16INK4a protein is an inhibitor of cyclin-dependent-kinase 4 (CDK4), thus blocking the cell cycle at the G1 phase through the ... Detection of homozygous deletions of the cyclin-dependent kinase 4 inhibitor (p16) gene in acute lymphoblastic leukemia and ... p16 and p15 are both cycline D kinase inhibitors (CDK4/6), thus playing a role in the arrest of the cell cycle at the G1 phase ...
Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells | PNAS
Previous studies investigating the roles of the cyclin-dependent kinase inhibitors p21Cip1, p27Kip1, p16INK4a/p19ARF, and p18 ... Recently, several negative regulators of the cell cycle, such as the cyclin-dependent kinase inhibitors p21Cip1, p27Kip1, and ... in particular the CIP/KIP and INK4 family of cyclin-dependent kinase inhibitors, and they have revealed that the loss of these ... The action of the INK4 and CIP/KIP families of cell cycle inhibitors on Cdk4/6- or Cdk2-containing complexes, respectively, is ...
Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts | PNAS
... p18INK4c, and p19INK4d (reviewed in ref. 10). p16 was the first member of the INK4 family characterized and was isolated based ... MAP kinase, cyclin D1, the cyclin-dependent inhibitors, p21 and p16. The percentage of the population actively undergoing DNA ... we examined the expression levels and interaction of the Rb kinases, CDK4 and CDK6, and the cyclin-dependent kinase inhibitors ... Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. David A ...
Cyclin-Dependent Kinase 6 Summary Report | CureHunter
It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18. ... Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE ... Protein Kinases: 9706*Protein-Serine-Threonine Kinases: 1353*Cyclin-Dependent Kinases: 639*Cyclin-Dependent Kinase 6: 44*human ... Proline-Directed Protein Kinases: 26*Cyclin-Dependent Kinases: 639*Cyclin-Dependent Kinase 6: 44*human CDK6 protein ...
Cdk4 and Cdk6CDK6CDKsMitogen-activaINK4ProteinsCip1Ink4aKip1CDKN2CInhibitGenesINK4dCDK2RegulatorsHomologInhibitsRegulatorP18INK4CReceptor tyrosiCkisTyrosine kinase inhPhosphorylationTumorInhibitoryCDKIsExpression of the cell cycle inhibitorVitroMRNARegulateClasses of CDK inhibitorsProtein kinasesTranscriptionRetinoblastomaNegativelyMiceRegulationKip2PotentProgressionHistone deacetylaPharmacological CDK inhibitorsCDKN2BApoptosis
Cdk4 and Cdk610
- 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 is a cyclin-dependent kinase (CDK) inhibitor, and binds CDK4 and CDK6 and inhibits their kinase activity. (takarabio.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)
- Furthermore, the senescent-cell-cycle arrest occurs prior to the accumulation of the Cdk4-Cdk6 inhibitor p16 Ink4a , suggesting that p21 may be sufficient for this event. (asm.org)
- Instead, the cyclin D1-Cdk4 and cyclin D1-Cdk6 complexes in these cells are associated with an increased amount of p21, suggesting that p21 may be responsible for inactivation of both cyclin E- and cyclin D1-associated kinase activity at the early stage of senescence. (asm.org)
- Phosphorylation of pRb during G 1 phase is carried out by cyclin D-Cdk4 and cyclin D-Cdk6 (cyclin D-Cdk4/6) and cyclin E-Cdk2 complexes ( 44 , 50 , 55 ). (asm.org)
- 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. (lsbio.com)
- RT "Identification of G1 kinase activity for cdk6, a novel cyclin D RT partner. (genome.jp)
- RT "Transforming activity of Fbxo7 is mediated specifically through RT regulation of cyclin D/cdk6. (genome.jp)
- 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)
- 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)
- pRb releases E2F when the former is phosphorylated and inactivated by the cyclin D-cdk4-cdk6 kinase in G 1 and the cyclin E-cdk2 kinase at the G 1 -S boundary ( 4 , 28 , 33 ). (asm.org)
- 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)
- 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)
- 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)
- 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)
- Full activation of the cyclin-CDK holoenzymes requires phosphorylation at particular sites in CDKs. (springer.com)
- CDK activity is also negatively regulated by direct interaction with CDK inhibitors, which consist of two families, the inhibitor of CDK4 (INK4) family, which specifically inhibit cyclin D-associated kinases, and the kinase inhibitor protein (Cip/Kip) family, which inhibit most CDKs. (springer.com)
- CDK inhibitors, cyclins, and CDKs themselves) is a common mechanism responsible for out-of-control cell growth, the main characteristic in cancer. (springer.com)
- Thus, CDKs are attractive targets for both cancer therapy and neuroprotection, and numerous pharmacological CDK inhibitors have been reported. (springer.com)
- Cyclin-dependent kinases (Cdks) comprise a promising set of such targets. (aacrjournals.org)
- Cdks are activated in part by their association with cyclins. (aacrjournals.org)
- Cyclin-dependent kinases (CDKs) have been considered promising drug targets for a number of years, but most CDK inhibitors have failed rigorous clinical testing. (aspetjournals.org)
- Cancer is a disease of uncontrolled proliferation, and since CDKs are a central component of the cell cycle engine, great effort has been expended in developing CDK inhibitors as anticancer agents. (aspetjournals.org)
- Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). (biomedcentral.com)
- CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs). (biomedcentral.com)
- The progression of cells through the cell cycle is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs). (biomedcentral.com)
- Cyclins function as the positive regulators of CDKs. (biomedcentral.com)
- Cyclins and CDKs assemble into complexes with one another as cells progress through G1 phase, cyclins being required to activate the serine-threonine kinase activity of their catalytic partners. (biomedcentral.com)
- Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (biomedcentral.com)
- 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)
- Cells are driven through the cell cycle by a complex of two classes of proteins, cyclins and cyclin dependent kinases (CDKs). (biomedcentral.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 . (doctorabel.us)
- 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)
- 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)
- CDKN2C / p18 INK4c is a member of the INK4 family of cyclin-dependent kinase inhibitors. (lsbio.com)
- We examined the genomic status of cyclin-dependent kinase-4 and -6 inhibitors, p16 INK4 , p15 INK4B , and p18 , in 40 primary lung cancers and 31 metastatic lung cancers. (aacrjournals.org)
- Members of the INK4 family (p15, p16, p18, and p19) inhibit D-type cyclins, while CIP/KIP family members (p21, p27, and p57) inhibit E- and A-type cyclins ( 36 , 51 ). (asm.org)
- In addition, two groups of inhibitors, known as Cip/Kip and INK4 proteins, also regulate cdk activity. (aacrjournals.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)
- This process is in part regulated by a family of Cdk inhibitors (CKIs) called the Ink4 family (Inhibitors of Cdk4). (diva-portal.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)
- 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)
- 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 contrast, pRb-related proteins p107 and p130, which also decrease cyclin E-kinase activity, do not cause an accumulation of p27 KIP1 and induce senescence poorly. (asm.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)
- 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)
- 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)
- 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)
- 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)
- In investigating the mechanism by which pRb induces senescence, we have found that pRb causes a posttranscriptional accumulation of the cyclin-dependent kinase inhibitor p27 KIP1 that is accompanied by an increase in p27 KIP1 specifically bound to cyclin E and a concomitant decrease in cyclin E-associated kinase activity. (asm.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)
- 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  (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)
- However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 ( CDKN1B /p27 and other cyclin-dependent kinase inhibitor genes CDKN1A /p15, CDKN2C /p18, CDKN2B /p21). (biomedcentral.com)
- 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)
- Two critical pathways are delta-like 4 (DLL4)/Notch and BMP9/activin-like kinase-1 (ALK1), which can display cooperative signal transduction 1 , 2 and inhibit hypersprouting to maintain appropriate capillary density. (ahajournals.org)
- The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (biomedcentral.com)
- Another level of cell cycle regulation is affected by the cdk inhibitors, which bind to cdk or cdk-cyclin complexes and inhibit their kinase activity. (biomedcentral.com)
- 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)
- A derived MNTI cell line was sensitive to inhibitors of lysine demethylase, but not to compounds targeting other epigenetic regulators.In the absence of somatic copy number variations or mutations, the fully transformed phenotype of the MNTI may have arisen in infancy because of the combined effects of a germline CDKN2A mutation, tumor promoting somatic fusion genes and epigenetic deregulation. (ox.ac.uk)
- 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)
- 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)
- 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)
- RT "Cyclin-dependent kinase 6 inhibits proliferation of human mammary RT epithelial cells. (genome.jp)
- 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)
- 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)
- 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)
Tyrosine kinase inh4
- 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)
- 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)
- A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. (harvard.edu)
- These data, revealed in the absence of p53, suggest a cell-type specific tumor suppressing role for p18 Ink4c . (diva-portal.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)
Expression of the cell cycle inhibitor1
- 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)
- 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)
- It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18. (curehunter.com)
- 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)
- 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)
- CDK8 and cyclin C associate with the mediator complex and regulate transcription by several mechanisms. (wikipedia.org)
Classes of CDK inhibitors2
- MENIN induces the transcription of cyclin-dependent kinase inhibitors p18 and p27 . (doctorabel.us)
- 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)
- 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)
- The activity of these kinase complexes is negatively regulated by cyclin-dependent kinase inhibitors. (asm.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)
- SGK1-Sensitive Regulation of Cyclin-Dependent Kinase Inhibitor 1B (p27) in Cardiomyocyte Hypertrophy. (univ-paris5.fr)
- Unlike the other family members, p57 Kip2 has a unique role during embryogenesis and is the only CDK inhibitor required for embryonic development. (frontiersin.org)
- In contrast to other cyclin-dependent kinase inhibitors, p57 Kip2 expression diminishes during postnatal life and is reactivated in the adult heart under conditions of cardiac stress. (biomedcentral.com)
- 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)
- Flavopiridol (L86-8275, HMR 1275) is the first potent cdk inhibitor to enter clinical trials. (aacrjournals.org)
- The natural product cortistatin A is a potent and selective inhibitor of CDK8 and CDK19 . (wikipedia.org)
- Cyclin D1 is a key actor for the development and progression of various cancers including hematological malignancies. (biomedcentral.com)
- 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)
Pharmacological CDK inhibitors1
- These observations have prompted great interest in the development of pharmacological cdk inhibitors that could produce similar antitumor effects. (aacrjournals.org)
- Further, we determined that FGF4 regulates Cdkn2b through a MEKI/ERK-dependent pathway. (ubc.ca)