Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs.Blood Transfusion, Autologous: Reinfusion of blood or blood products derived from the patient's own circulation. (Dorland, 27th ed)Krypton: A noble gas that is found in the atmosphere. It has the atomic symbol Kr, atomic number 36, atomic weight 83.80, and has been used in electric bulbs.Fibrinolysis: The natural enzymatic dissolution of FIBRIN.GermanyEarthquakes: Sudden slips on a fault, and the resulting ground shaking and radiated seismic energy caused by the slips, or by volcanic or magmatic activity, or other sudden stress changes in the earth. Faults are fractures along which the blocks of EARTH crust on either side have moved relative to one another parallel to the fracture.Disasters: Calamities producing great damage, loss of life, and distress. They include results of natural phenomena and man-made phenomena. Normal conditions of existence are disrupted and the level of impact exceeds the capacity of the hazard-affected community.DNA Nucleotidylexotransferase: A non-template-directed DNA polymerase normally found in vertebrate thymus and bone marrow. It catalyzes the elongation of oligo- or polydeoxynucleotide chains and is widely used as a tool in the differential diagnosis of acute leukemias in man. EC 18.104.22.168.Erythropoiesis: The production of red blood cells (ERYTHROCYTES). In humans, erythrocytes are produced by the YOLK SAC in the first trimester; by the liver in the second trimester; by the BONE MARROW in the third trimester and after birth. In normal individuals, the erythrocyte count in the peripheral blood remains relatively constant implying a balance between the rate of erythrocyte production and rate of destruction.Erythroblasts: Immature, nucleated ERYTHROCYTES occupying the stage of ERYTHROPOIESIS that follows formation of ERYTHROID PRECURSOR CELLS and precedes formation of RETICULOCYTES. The normal series is called normoblasts. Cells called MEGALOBLASTS are a pathologic series of erythroblasts.Erythroid Cells: The series of cells in the red blood cell lineage at various stages of differentiation.Erythroid Precursor Cells: The cells in the erythroid series derived from MYELOID PROGENITOR CELLS or from the bi-potential MEGAKARYOCYTE-ERYTHROID PROGENITOR CELLS which eventually give rise to mature RED BLOOD CELLS. The erythroid progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E); BFU-E differentiate into CFU-E on stimulation by ERYTHROPOIETIN, and then further differentiate into ERYTHROBLASTS when stimulated by other factors.Cell Cycle: 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.DNA Nucleotidyltransferases: Enzymes that catalyze the incorporation of deoxyribonucleotides into a chain of DNA. EC 2.7.7.-.Receptors, Notch: A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN repeats in their cytoplasmic domains. The cytoplasmic domain of notch receptors is released upon ligand binding and translocates to the CELL NUCLEUS where it acts as transcription factor.Receptor, Notch2: A notch receptor that plays an important role in CELL DIFFERENTIATION in a variety of cell types. It is the preferentially expressed notch receptor in mature B-LYMPHOCYTES.Receptor, Notch1: A notch receptor that interacts with a variety of ligands and regulates SIGNAL TRANSDUCTION PATHWAYS for multiple cellular processes. It is widely expressed during EMBRYOGENESIS and is essential for EMBRYONIC DEVELOPMENT.p-Azobenzenearsonate: A hapten capable of eliciting both antibody formation and delayed hypersensitivity when bound to aromatic amino acids, polypeptides or proteins. It is used as an immunologic research tool.Precursor T-Cell Lymphoblastic Leukemia-Lymphoma: A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.Amyloid Precursor Protein Secretases: Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.Exome: That part of the genome that corresponds to the complete complement of EXONS of an organism or cell.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Melanoma: A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)gp100 Melanoma Antigen: A melanosome-associated protein that plays a role in the maturation of the MELANOSOME.Cancer Vaccines: Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.MART-1 Antigen: A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.Antigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.New YorkColforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.Fibroblast Growth Factor 2: A single-chain polypeptide growth factor that plays a significant role in the process of WOUND HEALING and is a potent inducer of PHYSIOLOGIC ANGIOGENESIS. Several different forms of the human protein exist ranging from 18-24 kDa in size due to the use of alternative start sites within the fgf-2 gene. It has a 55 percent amino acid residue identity to FIBROBLAST GROWTH FACTOR 1 and has potent heparin-binding activity. The growth factor is an extremely potent inducer of DNA synthesis in a variety of cell types from mesoderm and neuroectoderm lineages. It was originally named basic fibroblast growth factor based upon its chemical properties and to distinguish it from acidic fibroblast growth factor (FIBROBLAST GROWTH FACTOR 1).Veratridine: A benzoate-cevane found in VERATRUM and Schoenocaulon. It activates SODIUM CHANNELS to stay open longer than normal.Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., GENETIC ENGINEERING) is a central focus; laboratory methods used include TRANSFECTION and CLONING technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction.Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.Telomere Shortening: The loss of some TELOMERE sequence during DNA REPLICATION of the first several base pairs of a linear DNA molecule; or from DNA DAMAGE. Cells have various mechanisms to restore length (TELOMERE HOMEOSTASIS.) Telomere shortening is involved in the progression of CELL AGING.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.DNA, Mitochondrial: Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.Circadian Clocks: Biological mechanism that controls CIRCADIAN RHYTHM. Circadian clocks exist in the simplest form in cyanobacteria and as more complex systems in fungi, plants, and animals. In humans the system includes photoresponsive RETINAL GANGLION CELLS and the SUPRACHIASMATIC NUCLEUS that acts as the central oscillator.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Psychological Theory: Principles applied to the analysis and explanation of psychological or behavioral phenomena.Education, Graduate: Studies beyond the bachelor's degree at an institution having graduate programs for the purpose of preparing for entrance into a specific field, and obtaining a higher degree.Faculty: The teaching staff and members of the administrative staff having academic rank in an educational institution.Students: Individuals enrolled in a school or formal educational program.Education, Pharmacy, Graduate: Educational programs for pharmacists who have a bachelor's degree or a Doctor of Pharmacy degree entering a specific field of pharmacy. They may lead to an advanced degree.Faculty, Medical: The teaching staff and members of the administrative staff having academic rank in a medical school.Audiovisual Aids: Auditory and visual instructional materials.Teaching: The educational process of instructing.Pancreatic Neoplasms: Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).Atlases as Topic: Collections of illustrative plates, charts, etc., usually with explanatory captions.Protein S: The vitamin K-dependent cofactor of activated PROTEIN C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S; (PROTEIN S DEFICIENCY); can lead to recurrent venous and arterial thrombosis.Islets of Langerhans: Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.RNA, Ribosomal: The most abundant form of RNA. Together with proteins, it forms the ribosomes, playing a structural role and also a role in ribosomal binding of mRNA and tRNAs. Individual chains are conventionally designated by their sedimentation coefficients. In eukaryotes, four large chains exist, synthesized in the nucleolus and constituting about 50% of the ribosome. (Dorland, 28th ed)Cadaver: A dead body, usually a human body.
Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. (1/73)The D-type cyclins and their major kinase partners CDK4 and CDK6 regulate G0-G1-S progression by contributing to the phosphorylation and inactivation of the retinoblastoma gene product, pRB. Assembly of active cyclin D-CDK complexes in response to mitogenic signals is negatively regulated by INK4 family members. Here we show that although all four INK4 proteins associate with CDK4 and CDK6 in vitro, only p16(INK4a) can form stable, binary complexes with both CDK4 and CDK6 in proliferating cells. The other INK4 family members form stable complexes with CDK6 but associate only transiently with CDK4. Conversely, CDK4 stably associates with both p21(CIP1) and p27(KIP1) in cyclin-containing complexes, suggesting that CDK4 is in equilibrium between INK4 and p21(CIP1)- or p27(KIP1)-bound states. In agreement with this hypothesis, overexpression of p21(CIP1) in 293 cells, where CDK4 is bound to p16(INK4a), stimulates the formation of ternary cyclin D-CDK4-p21(CIP1) complexes. These data suggest that members of the p21 family of proteins promote the association of D-type cyclins with CDKs by counteracting the effects of INK4 molecules. (+info)
Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity. (2/73)Cell cycle regulatory proteins are important candidates for therapeutic tumour suppressors. Adenovirus vectors were constructed to overexpress cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 under the control of the murine cytomegalovirus immediate early gene promoter. These vectors directed the efficient expression of each of the cyclin kinase inhibitors and induced growth arrest, inhibited DNA synthesis, and prevented phosphorylation of the retinoblastoma protein (pRb) in cell lines expressing functional pRb. In pRb-deficient cells, expression of the cyclin kinase inhibitors was not effective in inhibiting DNA replication or growth arrest. Interestingly, three of the cyclin kinase inhibitors, p16, p18 and p27 were found to induce apoptotic death in transduced HeLa and A549 cells. When the vectors were tested for their ability to inhibit tumorigenicity in a polyomavirus middle T antigen model of murine breast carcinoma, expression of the cyclin kinase inhibitors resulted in a delay in tumour formation that varied from several weeks for the p19 expressing vector to greater than 25 weeks for the p27 expressing vector. When tumours were injected directly with the adenovirus vectors expressing the cyclin kinase inhibitors, only treatment with the vector expressing p16 resulted in a delay in tumour growth. (+info)
Mutation testing in melanoma families: INK4A, CDK4 and INK4D. (3/73)The INK4A gene which codes for the cyclin-dependent kinase (CDK) inhibitor INK4A or p16 underlies susceptibility to melanoma in some families. Germline mutations in the gene that codes for the target protein of p16, CDK4, underlie susceptibility in very rare families. We report mutation screening of the INK4A and CDK4 genes in 42 UK families. A total of nine families were identified with INK4A mutations and none with CDK4 exon 2 mutations. These mutations were in 8/22 (35%) families with three or more cases of melanoma and 1/20 (5%) families with only two cases. In one of these nine families a novel single base pair substitution was identified, Gly67Arg. In an attempt to identify another melanoma susceptibility gene, a member of the INK4 family, the p19 INK4D gene has been studied. The p19 gene was sequenced in DNA from the 42 UK families and six additional US families. No mutations were identified. (+info)
Postnatal neuronal proliferation in mice lacking Ink4d and Kip1 inhibitors of cyclin-dependent kinases. (4/73)Development of the central nervous system requires proliferation of neuronal and glial cell precursors followed by their subsequent differentiation in a highly coordinated manner. The timing of neuronal cell cycle exit and differentiation is likely to be regulated in part by inhibitors of cyclin-dependent kinases. Overlapping and sustained patterns of expression of two cyclin-dependent kinases, p19(Ink4d) and p27(Kip1), in postmitotic brain cells suggested that these proteins may be important in actively repressing neuronal proliferation. Animals derived from crosses of Ink4d- null with Kip1-null mice exhibited bradykinesia, proprioceptive abnormalities, and seizures, and died at about 18 days after birth. Metabolic labeling of live animals with bromodeoxyuridine at postnatal days 14 and 18, combined with immunolabeling of neuronal markers, showed that subpopulations of central nervous system neurons were proliferating in all parts of the brain, including normally dormant cells of the hippocampus, cortex, hypothalamus, pons, and brainstem. These cells also expressed phosphorylated histone H3, a marker for late G(2) and M-phase progression, indicating that neurons were dividing after they had migrated to their final positions in the brain. Increased proliferation was balanced by cell death, resulting in no gross changes in the cytoarchitecture of the brains of these mice. Therefore, p19(Ink4d) and p27(Kip1) cooperate to maintain differentiated neurons in a quiescent state that is potentially reversible. (+info)
INK4d-deficient mice are fertile despite testicular atrophy. (5/73)The INK4 family of cyclin-dependent kinase (CDK) inhibitors includes four 15- to 19-kDa polypeptides (p16(INK4a), p15(INK4b), p18(INK4c), and p19(INK4d)) that bind to CDK4 and CDK6. By disrupting cyclin D-dependent holoenzymes, INK4 proteins prevent phosphorylation of the retinoblastoma protein and block entry into the DNA-synthetic phase of the cell division cycle. The founding family member, p16(INK4a), is a potent tumor suppressor in humans, whereas involvement, if any, of other INK4 proteins in tumor surveillance is less well documented. INK4c and INK4d are expressed during mouse embryogenesis in stereotypic tissue-specific patterns and are also detected, together with INK4b, in tissues of young mice. INK4a is expressed neither before birth nor at readily appreciable levels in young animals, but its increased expression later in life suggests that it plays some checkpoint function in response to cell stress, genotoxic damage, or aging per se. We used targeted gene disruption to generate mice lacking INK4d. These animals developed into adulthood, had a normal life span, and did not spontaneously develop tumors. Tumors did not arise at increased frequency in animals neonatally exposed to ionizing radiation or the carcinogen dimethylbenzanthrene. Mouse embryo fibroblasts, bone marrow-derived macrophages, and lymphoid T and B cells isolated from these animals proliferated normally and displayed typical lineage-specific differentiation markers. Males exhibited marked testicular atrophy associated with increased apoptosis of germ cells, although they remained fertile. The absence of tumors in INK4d-deficient animals demonstrates that, unlike INK4a, INK4d is not a tumor suppressor but is instead involved in spermatogenesis. (+info)
Distinct versus redundant properties among members of the INK4 family of cyclin-dependent kinase inhibitors. (6/73)p16(INK4a), p15(INK4b), p18(INK4c) and p19(INK4d) comprise a family of cyclin-dependent kinase inhibitors and tumor suppressors. We report that the INK4 proteins share the ability to arrest cells in G1, and interact with CDK4 or CDK6 with similar avidity. In contrast, only p18 and particularly p19 are phosphorylated in vivo, and each of the human INK4 proteins shows unique expression patterns dependent on cell and tissue type, and differentiation stage. Thus, the INK4 proteins harbor redundant as well as non-overlapping properties, suggesting distinct regulatory modes, and diverse roles for the individual INK4 family members in cell cycle control, cellular differentiation, and multistep oncogenesis. (+info)
Stat3-dependent induction of p19INK4D by IL-10 contributes to inhibition of macrophage proliferation. (7/73)We have previously reported that IL-10 inhibits proliferation of normal bone marrow-derived macrophages and of the monocyte/macrophage cell line J774. Activation of Stat3 was shown to be necessary and sufficient to mediate inhibition of proliferation. To investigate further the mechanism of growth arrest, we examined the effect of IL-10 on expression of cell cycle inhibitors. We found that IL-10 treatment increases expression of the cyclin-dependent kinase inhibitors p19INK4D and p21CIP1 in macrophages. IL-10 cannot induce p19INK4D expression or block proliferation when Stat3 signaling is blocked by a dominant negative Stat3 or a mutant IL-10Ralpha which does not recruit Stat3 in J774 cells, whereas p21CIP1 induction is not affected. An inducibly active Stat3 (coumermycin-dimerizable Stat3-Gyrase B), which suppresses J774 cell proliferation, also induced p19INK4D expression. Sequencing of the murine p19INK4D promoter revealed two candidate Stat3 binding sites, and IL-10 treatment activated a reporter gene controlled by this promoter. These data suggest that Stat3-dependent induction of p19INK4D mediates inhibition of proliferation. Enforced expression of murine p19INK4D cDNA J774 cells significantly reduced their proliferation. Use of antisense p19INK4D and analysis of p19INK4D-deficient macrophages confirmed that p19INK4D is required for optimal inhibition of proliferation by IL-10, and indicated that additional IL-10 signaling events contribute to this response. These data indicate that Stat3-dependent induction of p19INK4D and Stat3-independent induction of p21CIP1 are important components of the mechanism by which IL-10 blocks proliferation in macrophages. (+info)
Ubiquitin/proteasome-mediated degradation of p19INK4d determines its periodic expression during the cell cycle. (8/73)Assembly and activity of the proto-oncogenic cyclin D/CDK4(6) complexes, the major driving force of G1 phase progression, is negatively regulated by a family of INK4 CDK inhibitors p16INK4a, p15INK4b, p18INK4c, and p19INK4d. Expression of the INK4 family members is controlled at the transcriptional level, through differential response to environmental and intracellular signals such as cytokines, oncogenic overload, or cellular senescence. Here we show that the periodic oscillation of the p19INK4d protein during the cell cycle is determined by the ubiquitin/proteasome-dependent mechanism, allowing the protein abundance to follow the changes in its mRNA expression. Within the INK4 family, this regulatory mode appears restricted to p19INK4d whose ubiquitination was dependent on the integrity of lysine 62, and binding to CDK4. These results highlight unexpected differences among the INK4 inhibitors, and suggest how p19INK4d may help regulate the rate of cyclin D/CDK4(6) complex formation, and thereby timely progression through the mammalian cell division cycle. Oncogene (2000) 19, 2870 - 2876 (+info)
"Entrez Gene: CDKN2D cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4)". Hirai H, Roussel MF, Kato JY, et al. (1995). " ... 2004). "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27( ... "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. Biol. 15 ... Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene. The protein encoded by this ...
Cyclin-dependent kinase 4
1995). "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. ... See also CDK inhibitor for inhibitors of various CDKs. Cyclin-dependent kinase 4 has been shown to interact with: CDC37, CDKN1B ... 1995). "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. ... "Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ...
"Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ... CDKN2C has been shown to interact with Cyclin-dependent kinase 4 and Cyclin-dependent kinase 6. GRCh38: Ensembl release 89: ... Cyclin-dependent kinase 4 inhibitor C is an enzyme that in humans is encoded by the CDKN2C gene. The protein encoded by this ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". Ewing RM, Chu P, Elisma F, Li H, Taylor P, ...
... are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Molecular and Cellular Biology. 15 (5): 2672-81. PMC ... Hirai H, Roussel MF, Kato JY, Ashmun RA, Sherr CJ (May 1995). "Novel INK4 proteins, p19 and p18, ... Cyclins function as regulators of cyclin-dependent kinases. Different cyclins exhibit distinct expression and degradation ... "Cyclin D- and E-dependent kinases and the p57(KIP2) inhibitor: cooperative interactions in vivo". Molecular and Cellular ...
p21 p53 Cyclin-dependent kinase Cyclin D "Entrez Gene: CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits ... CDKN2 CDK 4 Inhibitor Multiple Tumor Suppressor 1 (MTS1) TP16 ARF MLM P14 P19 In humans, p16 is encoded by the CDKN2A gene, ... p16 is a cyclin-dependent kinase (CDK) inhibitor that slows down the cell cycle by prohibiting progression from G1 phase to S ... "The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner". ...
Cyclin-dependent kinase 6
Furthermore, inhibitors of the INK4 family members like p15, p16, p18 and p19 inhibit the monomer of CDK6, preventing the ... "Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein ... 2003). "Expression of Cyclin-Dependent Kinase 6, but Not Cyclin-Dependent Kinase 4, Alters Morphology of Cultured Mouse ...
... serum amyloid A-activating factor 1 inhibits cell proliferation by the induction of cyclin-dependent protein kinase inhibitor ... during the neural differentiation of P19 EC cells". Biochem. Biophys. Res. Commun. 286 (5): 1087-97. doi:10.1006/bbrc.2001.5469 ... during the neural differentiation of P19 EC cells". Biochem. Biophys. Res. Commun. 286 (5): 1087-97. doi:10.1006/bbrc.2001.5469 ... are regulated by casein kinase II". Biochem. Biophys. Res. Commun. 262 (1): 198-205. doi:10.1006/bbrc.1999.1130. PMID 10448092 ...
It specifically recognizes and promotes the degradation of phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also ... "Chromosomal mapping of the genes for the human CDK2/cyclin A-associated proteins p19 (SKP1A and SKP1B) and p45 (SKP2)". ... Progression through the cell cycle is tightly regulated by cyclin-dependent kinases (CDKs), and their interactions with cyclins ... "Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated ...
List of MeSH codes (D12.776)
... cyclin-dependent kinase inhibitor p18 MeSH D12.776.624.776.355.400 - cyclin-dependent kinase inhibitor p19 MeSH D12.776.624.776 ... cyclin-dependent kinase inhibitor p15 MeSH D12.776.624.776.355.200 - cyclin-dependent kinase inhibitor p16 MeSH D12.776.624.776 ... cyclin-dependent kinase inhibitor p21 MeSH D12.776.624.776.355.600 - cyclin-dependent kinase inhibitor p27 MeSH D12.776.624.776 ... cyclin-dependent kinase 5 MeSH D12.776.167.200.067.900 - cyclin-dependent kinase 9 MeSH D12.722.214.171.1240.500 - cdc2 protein ...
It binds to F-box proteins (proteins containing an F-box motif), such as cyclin F, S-phase kinase-associated protein 2, and ... "Chromosomal mapping of the genes for the human CDK2/cyclin A-associated proteins p19 (SKP1A and SKP1B) and p45 (SKP2)". ... Wu G, Lyapina S, Das I, Li J, Gurney M, Pauley A, Chui I, Deshaies RJ, Kitajewski J (November 2001). "SEL-10 is an inhibitor of ... Fukuchi M, Imamura T, Chiba T, Ebisawa T, Kawabata M, Tanaka K, Miyazono K (2001). "Ligand-dependent degradation of Smad3 by a ...
Inhibitors of the MDM2-p53 interaction include the cis-imidazoline analog nutlin. Levels and stability of Mdm2 are also ... Honda R, Yasuda H (March 2000). "Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger ... This loop can be interfered with by kinases and genes like p14arf when p53 activation signals, including DNA damage, are high. ... Zhao L, Samuels T, Winckler S, Korgaonkar C, Tompkins V, Horne MC, Quelle DE (January 2003). "Cyclin G1 has growth inhibitory ...
The other ink recipe threads are dying, and nobody wants to read through 10 pages to find what they want. Therefore I decided to start a new one. This thread is intended for those who dont know much about ink to start learning. Im giving it my best shot to answer all of your questions. Now, lets ...
Investigator of human and animal mysteries since 1960. Swamp Thing character "Coleman Wadsworth" in #4:7 and more in #4:8, is a tribute. Author of over 35 books, including The Unidentified (1975), Mysterious America (1983/2007), Suicide Clusters (1987), Cryptozoology A to Z (1999), Bigfoot! (2003), The Copycat Effect (2004), and field guides. Educated in anthropology-zoology at SIU-Carbondale, and psychiatric social work at Simmons College School of Social Work. Began doctoral work in anthropology (Brandeis University) and family violence (UNH). Taught at NE universities (1980 to 2003), while concurrently a senior researcher at the Muskie School (1983 to 1996), before retiring to write, lecture, consult, & open museum. Popular documentary course was taught for 23 semesters; appeared on C2C, The Larry King Show, MonsterQuest, Lost Tapes, In Search Of, and other tv programs. Loren Coleman is a dedicated father (Caleb, Malcolm, Des), cryptozoologist, media consultant, and baseball fan ...
Forensic Analysis of Pens & Inks. Video link. http://www.youtube.com/watch?v=I34tz5nIPCs 9 min. Inks appearing on questioned documents may be examined for the purpose of comparing with other inks on the same document, with ink on other documents or even with ink in seized pens....
cattattoo #crazycatlady #catofinstagram #ink #inked #inkart #tattooart #tattoolife #tattoolove #tattoopassion ...
#cattattoo #crazycatlady #catofinstagram #ink #inked #inkart #tattooart #tattoolife #tattoolove #tattoopassion #tattooinspiration #tattocommunity #lamoglietatuata #thetattooedwife
White Ink found in: Higgins Pigment-Based Drawing Ink, Higgins Super White Pigment-Based Waterproof Drawing Ink, Handy Art Block Ink, Jacquard Screen..
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.
was one of the ladies. It waited 5 years now to get finished. Due to the fact that Im teaching a Dear Jane class locally Ill get practice with the border and scalloped edges on this UFO - ...
Page one so far. Ive still got to tidy it up and add a bit more line work. I am enjoying doing this little project. its a good bi ...
Tsvangirai added, "If Zimbabwe proceeds to use the BVR system, which Zanu PF is not keen to do, we are also aware of plans to have Nikuv International Projects work with some named Indian companies in hacking or engaging in cyber- attacks on the whole electoral system once it becomes clear that the results are not going in Zanu PFs favour.". "We are aware therefore that plans are afoot to either control or derail the BVR process, frustrate voter registration and the actual voting in perceived opposition strongholds. We know as well that there are plans to tamper with silver nitrate and other inks such as UV ink that may be used in order to fudge the result of the next election.". Tsvangirai said the national executive resolved that the MDC-T, together other parties, would "utilize all legitimate and constitutionally permissible avenues at our disposal to stop this daylight theft".. "Whether in the courts or in the streets, we shall fight all attempts to steal the next election and we fully ...
The World Leader In Wide Format Ink. STS Inks is recognized as a world leader in wide format inks. All of our ink replacements match both OEM ink color and performance. STS Inks are manufactured to meet the industrys highest standards.
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.. ...
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.
Absence of p19INK4d Leads to a Progressive Age-Dependen | Open-i
Absence of p19INK4d Leads to a Progressive Age-Dependent Increase in the Number of MKs in BM and Spleen of Mice(A and B) Number ... Cyclin-Dependent Kinase Inhibitor p19/deficiency/genetics*/metabolism. *DNA Damage*. *Hematopoietic Stem Cells/cytology*/ ... fig5: Absence of p19INK4d Leads to a Progressive Age-Dependent Increase in the Number of MKs in BM and Spleen of Mice(A and B) ... fig5: Absence of p19INK4d Leads to a Progressive Age-Dependent Increase in the Number of MKs in BM and Spleen of Mice(A and B) ...https://openi.nlm.nih.gov/detailedresult.php?img=PMC4264042_gr5&req=4
GO Gene List
Cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4). NM_001800. NM_079421. Gene Info. ... Cyclin-dependent kinase inhibitor 1B (p27, Kip1). NM_004064. Gene Info. CDKN2A. Cyclin-dependent kinase inhibitor 2A. NM_ ... Cyclin-dependent kinase inhibitor 1A (p21, Cip1). NM_001220778. NM_000389. NM_078467. NM_001220777. Gene Info. ... Cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4). NM_001262. NM_078626. Gene Info. ...https://cgap.nci.nih.gov/Genes/GoGeneQuery?PAGE=1&ORG=Hs&GOID=0045926
cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4). Protein Similarities Based on Shared Motif Content. ... MF] cyclin-dependent protein kinase inhibitor activity *[MF] protein kinase binding BioCarta Pathways. ... BP] regulation of cyclin-dependent protein kinase activity *[BP] response to UV *[BP] response to retinoic acid *[BP] response ... CDKN2D, cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4). Sequence ID:. NM_001800. NM_079421. ...https://cgap.nci.nih.gov/Genes/GeneInfo?ORG=Hs&CID=435051&LLNO=1032
Cdkn2d - ddPCR Probe - Digital PCR | PrimePCR | Bio-Rad
Cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4). Aliases:. INK4d, p19, p19INK4d. ...http://www.bio-rad.com/en-us/prime-pcr-assays/assay/dmmucpe5110040-primepcr-ddpcr-expression-probe-assay-cdkn2d-mouse
Durchsuchen nach Personen
Identification of calpain cleavage sites in the G1 cyclin-dependent kinase inhibitor p19(INK4d). In: Biological Chemistry, Vol ... Jochum, Marianne und Bittner, A. (1983): Inter-alpha-Trypsin Inhibitor of Human Serum. An Inhibitor of Polymorphonuclear ... Fritz, Hans; Collins, John und Jochum, Marianne (1992): Proteinase inhibitor candidates for therapy of enzyme-inhibitor ... Effects of proteinase inhibitors and of leukocyte depletion. In: Blood, Vol. 79, Nr. 11: S. 3071-3075 [PDF, 1MB] ...https://epub.ub.uni-muenchen.de/view/autoren/Jochum=3AMarianne=3A=3A.html
Unexpected role for p19INK4d in post-transcriptional regulation of GATA1 and modulation of human terminal erythropoiesis |...
Knockdown of cyclin-dependent kinase inhibitor p19INK4d impairs human terminal erythroid differentiation by decreasing GATA1 ... cyclin-dependent kinases and cyclin-dependent kinase inhibitors (CDKI), yet their roles in erythropoiesis remain to be fully ... Further biochemical analysis revealed that p19INK4d directly binds to Raf kinase inhibitor PEBP1 and that p19INK4d knockdown ... As GATA1 protein is protected by nuclear HSP70, we examined the effects of p19INK4d knockdown on HSP70 and found that p19INK4d ...http://www.bloodjournal.org/content/early/2016/11/22/blood-2016-09-739268?sso-checked=true
MSX2 msh homeobox 2 [Homo sapiens (human)] - Gene - NCBI
... of proliferation in developing human tooth germs by MSX homeodomain proteins and cyclin-dependent kinase inhibitor p19,sup, ... p19(INK4d) plays an active role during human tooth development along with MSX1 and MSX2 Title: Regulation ...https://www.ncbi.nlm.nih.gov/gene/4488
CDKN2D - Wikipedia
"Entrez Gene: CDKN2D cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4)". Hirai H, Roussel MF, Kato JY, et al. (1995). " ... 2004). "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27( ... "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. Biol. 15 ... Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene. The protein encoded by this ...https://en.wikipedia.org/wiki/CDKN2D
Cdkn2d - PrimePCR Assay and Template | Life Science | Bio-Rad
Cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4) Assay Type: SYBR® Green Assay Design: Intron-spanning Application: ... Cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4) Assay Type: Probe Assay Design: Intron-spanning Application: Gene ... Cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4) Assay Type: EvaGreen Application: Gene Expression Unique Assay ID: ... Cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4) Assay Type: Probe Application: Gene Expression Unique Assay ID: ...http://www.bio-rad.com/en-us/prime-pcr-assays/gene/cdkn2d-mouse
Cells | Free Full-Text | The Myc Road to Hearing Restoration | HTML
The cyclin-dependent kinase inhibitors p19(Ink4d) and p27(Kip1) are coexpressed in select retinal cells and act cooperatively ... including the cyclins, cyclin dependent kinases (Cdks), Cdk inhibitors such as the Kip/Cip and Ink families, tumor suppressors ... Role of cyclin D1 and cyclin-dependent kinase inhibitors. Dev. Biol. 2010, 337, 134-146. [Google Scholar] ... The differentiated state is further maintained by high levels of cyclin dependent kinase inhibitors (CDKIs) and retinoblastoma ...https://www.mdpi.com/2073-4409/1/4/667/htm
Gene Set - basophilic leukemia cell line
cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4) 0.812309 CTSG cathepsin G 0.810221 ... G protein-coupled receptor kinase interacting ArfGAP 1 0.478923 CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4 ... cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) 0.292436 KCNJ12 potassium channel, inwardly rectifying subfamily J, ... cyclin-dependent kinase inhibitor 1A (p21, Cip1) 0.229568 POU5F1B POU class 5 homeobox 1B 0.229299 ...https://amp.pharm.mssm.edu/Harmonizome/gene_set/basophilic+leukemia+cell+line/TISSUES+Text-mining+Tissue+Protein+Expression+Evidence+Scores
Genetic rescue of cell number in a mouse model of microphthalmia: interactions between Chx10 and G1-phase cell cycle regulators...
The cyclin-dependent kinase inhibitors p19(Ink4d) and p27(Kip1) are coexpressed in select retinal cells and act cooperatively ... Assembly of cyclin D-dependent kinase and titration of p27Kip1 regulated by mitogen-activated protein kinase kinase (MEK1). ... Nakayama, K. (1998). Cip/Kip cyclin-dependent kinase inhibitors: brakes of the cell cycle engine during development. BioEssays ... Cunningham, J. J. and Roussel, M. F. (2001). Cyclin-dependent kinase inhibitors in the development of the central nervous ...http://dev.biologists.org/content/130/3/539
IMP: Integrative Multi-species Prediction
cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4). 0.010. Mmp12. matrix metallopeptidase 12. 0.010. ... nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha. 0.014. ...http://imp.princeton.edu/predictions/process/mouse-context-global/7924/?gene=61982
IMP: Integrative Multi-species Prediction
cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4). 0.024. Ctsd. cathepsin D. 0.023. ... serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1. 0.718. ...http://imp.princeton.edu/predictions/process_ortho/rat-context-global/11041/
Cell Senescence in Myxoid/Round Cell Liposarcoma
... coexpressed with cyclin dependent kinase inhibitors P16, P19, and P27 (also known as CDKN2A, CDKN2D, and CDKN1B, resp.) . ... Previous analysis of cell cycle regulatory proteins revealed a prominent expression of G1-cyclins, cyclin dependent kinases, ... regulating proteins in MLS/RCLS revealed a prominent expression of growth promoting G1 cyclins and cyclin dependent kinases ( ... Recent results from investigations of senescent cells suggest that they express G1 cyclins, CDKs, and their inhibitors as well ...https://www.hindawi.com/journals/sarcoma/2014/208786/
Phosphorylation-induced unfolding regulates p19INK4d during the human cell cycle | PNAS
Cyclin-dependent protein kinases and their inhibitors, such as p19INK4d, regulate the different stages of the cell cycle. Here ... Cell cycle progression is tightly regulated by cyclin-dependent kinases (CDKs). The ankyrin-repeat protein p19INK4d functions ... which dissociates its cyclin-dependent protein kinase-inhibitory complex and primes p19INK4d for cellular degradation. Our ... dependent protein kinases (CDK1), respectively, leads to local unfolding of the three N-terminal ankyrin repeats of p19INK4d. ...http://www.pnas.org/content/115/13/3344
Evaluation of Selective γ-Secretase Inhibitor PF-03084014 for Its Antitumor Efficacy and Gastrointestinal Safety to Guide...
Notch inhibition caused a dose-dependent cell cycle arrest (Fig. 2) and upregulation of cyclin-dependent kinase inhibitor p27 ... p19 INK4d) and CDKN1b (p27 Kip1) and the subsequent derepression of Rb. These results further support the role of Notch in cell ... In accordance with cell cycle block, we observed robust regulation of total Rb protein and cyclin dependent kinase inhibitor ... showed that inhibition of Notch pathway activity signature results in the upregulation of cyclin-dependent kinase inhibitors ...http://mct.aacrjournals.org/content/9/6/1618
Cyclin-dependent kinase 4 - Wikipedia
"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/ ...https://en.wikipedia.org/wiki/CDK4
Creating a unified theory of aging - Aging Theories - LONGECITY
... and lipofuscin deposition in pyramidal neurons associated with upregulation of cyclin-dependent kinase inhibitors p19, p27, and ... These included increased abundance of the messenger RNA encoding the CDK inhibitors p16(Ink4a), p19(Arf), and p21(Cip1); a ... Zhous laboratory is now developing inhibitors to Zmpste 24, which he hopes to apply to tumors. These inhibitors should ... Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Teschendorff et al. 2010. ...https://www.longecity.org/forum/topic/7029-creating-a-unified-theory-of-aging/
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 ...http://www.bloodjournal.org/content/100/8/2957?ijkey=0dd972d0b75c32e0a0737436ef03a3e2355508cb&keytype2=tf_ipsecsha&sso-checked=true
Exploiting the Mutanome for Tumor Vaccination | Cancer Research
... cyclin-dependent kinase inhibitor 2A, p19Arf and p16Ink4a) is homozygously deleted and that neither activating mutations in ... cyclin-dependent kinase inhibitor 2A, p16Ink4A). To identify possibly immunogenic mutations, we identified 3,570 somatic point ... a cell membrane-bound receptor tyrosine kinase of the mitogen-activated protein kinase/extracellular signal-regulated kinase ( ... a Trrap mutation occurs at p.K2783R which is predicted to disturb the overlapping phosphatidylinositol kinase-related kinase ...https://cancerres.aacrjournals.org/content/72/5/1081?ijkey=af4f5007c58ab0844b003d655e7c4c29cefaabb4&keytype2=tf_ipsecsha
Voltage-Activated K+ Channels and Membrane Depolarization Regulate Accumulation of the Cyclin-Dependent Kinase Inhibitors...
... lacking the cyclin-dependent kinase inhibitors p16INK4a and p19ARF. Our results demonstrate that blockage of K+ channels and ... cyclins and cyclin-dependent kinase inhibitors (cdkis) known to regulate cell cycle progression through this phase are affected ... 1997) Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of oligodendrocyte differentiation. EMBO J ... Blockage of K+ channels and membrane depolarization also caused accumulation of the cyclin-dependent kinase inhibitors p27Kip1 ...http://www.jneurosci.org/content/19/13/5380
Deletion of Shp2 in the Brain Leads to Defective Proliferation and Differentiation in Neural Stem Cells and Early Postnatal...
Bmi-1 promotes neural stem cell proliferation by repressing cyclin-dependent kinase inhibitors such as p16INK4a or p19INK4d (3 ... MEK inhibitor PD98059 (Cell Signaling), c-Myc inhibitor 10058-F4 (Calbiochem), and Shp2 inhibitor (Wu et al., unpublished data ... The Stat3 inhibitor significantly attenuated astroglial differentiation (Fig. 5E and G). In addition, an Shp2 inhibitor ... NSCs were treated with a pharmacological MEK inhibitor (PD98059) and c-Myc inhibitor (10058-F4) and were evaluated for self- ...https://mcb.asm.org/content/27/19/6706?ijkey=88d47f04dd4517b1416acea625ba696a99a4ffc9&keytype2=tf_ipsecsha
Myelodysplastic syndromes: molecular pathogenesis and genomic changes | SpringerLink
Molecular analysis of the cyclin-dependent kinase inhibitor genes, p15, p16, p18 and p19 in the myelodysplastic syndromes. Leuk ... a mechanism requiring protein kinase C, calmodulin-dependent kinase II, ERK, and c-Src. J Biol Chem 280:34617-34625PubMed ... Roboz GJ, Giles FJ, List AF et al (2006) Phase 1 study of PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor ... Muller-Tidow C, Wang W, Idos GE et al (2001) Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at ...https://link.springer.com/article/10.1007%2Fs00277-008-0502-z
Type-I Interferon Receptor Deficiency Reduces Lupus-like Disease in NZB Mice | JEM
... cyclin-dependent kinases (CDK4, cdc2), cyclin-dependent kinase inhibitors (CDKI p16, p18, p19, p21), and a housekeeping gene ( ... G1 arrest and high expression of cyclin kinase and apoptosis inhibitors in accumulated activated/ memory phenotype CD4+ cells ... Cyclins and cell cycle checkpoints. Annu. Rev. Pharmacol. Toxicol. 39:295-312. ... Genesis and evolution of antichromatin autoantibodies in murine lupus implicates T-dependent immunization with self antigen. J ...http://jem.rupress.org/content/197/6/777?ijkey=a99d815578eaca868baabe69bafc0eb859f815dc&keytype2=tf_ipsecsha
- p19 INK4d controls hematopoietic stem cells in a cell-autonomous manner during genotoxic stress and through the microenvironment during aging. (nih.gov)
- Knockdown of cyclin-dependent kinase inhibitor p19 INK4d impairs human terminal erythroid differentiation by decreasing GATA1 protein levels. (bloodjournal.org)
- GATA1 protein level is regulated by p19 INK4d via PEBP1-pERK-HSP70-GATA1 pathway. (bloodjournal.org)
- We show here that p19 INK4d , a member of CDKI family, is abundantly expressed in erythroblasts and that p19 INK4d knockdown delayed erythroid differentiation, inhibited cell growth, led to increased apoptosis and generation of abnormally nucleated late stage erythroblasts. (bloodjournal.org)
- Unexpectedly, p19 INK4d knockdown did not affect cell cycle. (bloodjournal.org)
- As GATA1 protein is protected by nuclear HSP70, we examined the effects of p19 INK4d knockdown on HSP70 and found that p19 INK4d knockdown led to decreased expression of HSP70 and its nuclear localization. (bloodjournal.org)
- Further biochemical analysis revealed that p19 INK4d directly binds to Raf kinase inhibitor PEBP1 and that p19 INK4d knockdown increased the expression of PEBP1 that in turn led to reduced ERK activation. (bloodjournal.org)
- Thus we have identified an unexpected role for p19 INK4d via a novel PEBP1-pERK-HSP70-GATA1 pathway. (bloodjournal.org)
- Cyclin-dependent protein kinases and their inhibitors, such as p19 INK4d , regulate the different stages of the cell cycle. (pnas.org)
- Here, we demonstrate how sequential phosphorylation of p19 INK4d at two sites first destabilizes and then unfolds the N-terminal half of the protein, which dissociates its cyclin-dependent protein kinase-inhibitory complex and primes p19 INK4d for cellular degradation. (pnas.org)
- Here, we combine cell and structural biology methods to unravel the mechanism by which p19 INK4d controls cell cycle progression. (pnas.org)
- We delineate how the stepwise phosphorylation of p19 INK4d Ser66 and Ser76 by cell cycle-independent (p38) and -dependent protein kinases (CDK1), respectively, leads to local unfolding of the three N-terminal ankyrin repeats of p19 INK4d . (pnas.org)
- This dissociates the CDK6-p19 INK4d inhibitory complex and, thereby, activates CDK6. (pnas.org)
- CDK6 triggers entry into S-phase, whereas p19 INK4d is ubiquitinated and degraded. (pnas.org)
- Our findings reveal how signaling-dependent p19 INK4d unfolding contributes to the irreversibility of G1/S transition. (pnas.org)
- showed that inhibition of Notch pathway activity signature results in the upregulation of cyclin-dependent kinase inhibitors CDKN2D (p19 INK4d) and CDKN1b (p27 Kip1) and the subsequent derepression of Rb. (aacrjournals.org)
- Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene. (wikipedia.org)
- Previous studies of cell cycle regulating proteins in MLS/RCLS revealed a prominent expression of growth promoting G1 cyclins and cyclin dependent kinases (CDK), coexpressed with cyclin dependent kinase inhibitors P16, P19, and P27 (also known as CDKN2A, CDKN2D, and CDKN1B, resp. (hindawi.com)
- 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)
- 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)
- Collectively, these results suggest that simvastatin induces apoptosis in tumor cells and its anti-proliferative activity was accompanied by inhibition of cyclin-dependent kinases and cyclins, whereas CDK inhibitors p19 and p27 were enhanced. (biomedsearch.com)
- The discovery of activating Notch1 mutations in T-ALL has made the Notch pathway an attractive target for the development of small molecule drugs, with γ-secretase inhibitors (GSI) having the most immediate therapeutic potential ( 10 ). (aacrjournals.org)
- Mutations shared among patients suffering from one tumor entity allow targeted approaches, as exemplified by small-molecule inhibitors targeting the bcr-abl translocation present in 90% of chronic myelogenous leukemia patients. (aacrjournals.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)
- 13 ]. This pattern suggested that the growth promoting cyclin/CDK activity was counteracted by CDK inhibitors and this could explain the low frequency of proliferating cells identified by Ki67 and cyclin A staining (typically less than 8 and 4 percent, resp. (hindawi.com)
- 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)