InkCyclin-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.Cyclin-Dependent Kinase Inhibitor p15: An INK4 cyclin-dependent kinase inhibitor containing four ANKYRIN-LIKE REPEATS. INK4B is often inactivated by deletions, mutations, or hypermethylation in HEMATOLOGIC NEOPLASMS.Tumor Suppressor Protein p14ARF: A gene product of the p16 tumor suppressor gene (GENES, P16). It antagonizes the function of MDM2 PROTEIN (which regulates P53 TUMOR SUPPRESSOR PROTEIN by targeting it for degradation). p14ARF is produced from the beta mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced alpha transcript, is CYCLIN-DEPENDENT KINASE INHIBITOR P16. Both p16 gene products have tumor suppressor functions.Cyclin-Dependent Kinase Inhibitor p18: An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN-LIKE REPEATS. Aberrant expression of this protein has been associated with deregulated EPITHELIAL CELL growth, organ enlargement, and a variety of NEOPLASMS.Cyclin-Dependent Kinase Inhibitor p19: An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN REPEATS. Aberrant expression of this protein has been associated with TESTICULAR CANCER.Genes, p16: Tumor suppressor genes located on human chromosome 9 in the region 9p21. This gene is either deleted or mutated in a wide range of malignancies. (From Segen, Current Med Talk, 1995) Two alternatively spliced gene products are encoded by p16: CYCLIN-DEPENDENT KINASE INHIBITOR P16 and TUMOR SUPPRESSOR PROTEIN P14ARF.Cell Aging: The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.Cyclin-Dependent Kinase 4: Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.Cyclin-Dependent Kinase 6: Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.Retinoblastoma Protein: 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.Chromosomes, Human, Pair 9: A specific pair of GROUP C CHROMSOMES of the human chromosome classification.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.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.Genes, Tumor Suppressor: Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Polycomb Repressive Complex 1: A multisubunit polycomb protein complex with affinity for CHROMATIN that contains methylated HISTONE H3. It contains an E3 ubiquitin ligase activity that is specific for HISTONE H2A and works in conjunction with POLYCOMB REPRESSIVE COMPLEX 2 to effect EPIGENETIC REPRESSION.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.Cyclin-Dependent Kinase Inhibitor p21: A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.PrintingTumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.Ink Blot Tests: Projective tests utilizing ink blots to which a subject responds. They are used in personality diagnosis.Cyclins: A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.Tattooing: The indelible marking of TISSUES, primarily SKIN, by pricking it with NEEDLES to imbed various COLORING AGENTS. Tattooing of the CORNEA is done to colorize LEUKOMA spots.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Polymorphism, Single-Stranded Conformational: Variation in a population's DNA sequence that is detected by determining alterations in the conformation of denatured DNA fragments. Denatured DNA fragments are allowed to renature under conditions that prevent the formation of double-stranded DNA and allow secondary structure to form in single stranded fragments. These fragments are then run through polyacrylamide gels to detect variations in the secondary structure that is manifested as an alteration in migration through the gels.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.G1 Phase: The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.DNA, Neoplasm: DNA present in neoplastic tissue.Genes, p53: Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.Cyclin D1: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Cervical Intraepithelial Neoplasia: A malignancy arising in uterine cervical epithelium and confined thereto, representing a continuum of histological changes ranging from well-differentiated CIN 1 (formerly, mild dysplasia) to severe dysplasia/carcinoma in situ, CIN 3. The lesion arises at the squamocolumnar cell junction at the transformation zone of the endocervical canal, with a variable tendency to develop invasive epidermoid carcinoma, a tendency that is enhanced by concomitant human papillomaviral infection. (Segen, Dictionary of Modern Medicine, 1992)Genes, Retinoblastoma: Tumor suppressor genes located on human chromosome 13 in the region 13q14 and coding for a family of phosphoproteins with molecular weights ranging from 104 kDa to 115 kDa. One copy of the wild-type Rb gene is necessary for normal retinal development. Loss or inactivation of both alleles at this locus results in retinoblastoma.CpG Islands: Areas of increased density of the dinucleotide sequence cytosine--phosphate diester--guanine. They form stretches of DNA several hundred to several thousand base pairs long. In humans there are about 45,000 CpG islands, mostly found at the 5' ends of genes. They are unmethylated except for those on the inactive X chromosome and some associated with imprinted genes.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.Genes, ras: Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Cyclin D: A cyclin subtype that is specific for CYCLIN-DEPENDENT KINASE 4 and CYCLIN-DEPENDENT KINASE 6. Unlike most cyclins, cyclin D expression is not cyclical, but rather it is expressed in response to proliferative signals. Cyclin D may therefore play a role in cellular responses to mitogenic signals.Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.Uterine Cervical Neoplasms: Tumors or cancer of the UTERINE CERVIX.Carcinoma, Squamous Cell: A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Polycomb-Group Proteins: A family of proteins that play a role in CHROMATIN REMODELING. They are best known for silencing HOX GENES and the regulation of EPIGENETIC PROCESSES.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)Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Sepia: A genus of cuttlefish in the family Sepiidae. They live in tropical, subtropical and temperate waters in most oceans.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.RNA, Messenger: 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.Ki-67 Antigen: A CELL CYCLE and tumor growth marker which can be readily detected using IMMUNOCYTOCHEMISTRY methods. Ki-67 is a nuclear antigen present only in the nuclei of cycling cells.Cell Line, Tumor: A cell line derived from cultured tumor cells.Cyclin-Dependent Kinase 2: A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Homozygote: An individual in which both alleles at a given locus are identical.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Mice, Knockout: 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.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Tumor Markers, Biological: Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.Papillomaviridae: A family of small, non-enveloped DNA viruses infecting birds and most mammals, especially humans. They are grouped into multiple genera, but the viruses are highly host-species specific and tissue-restricted. They are commonly divided into hundreds of papillomavirus "types", each with specific gene function and gene control regions, despite sequence homology. Human papillomaviruses are found in the genera ALPHAPAPILLOMAVIRUS; BETAPAPILLOMAVIRUS; GAMMAPAPILLOMAVIRUS; and MUPAPILLOMAVIRUS.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Cyclin-Dependent Kinase Inhibitor Proteins: A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION.Pongamia: A plant genus of the family FABACEAE. Members contain karanjin. Some species of this genus have been reclassified to other genera of FABACEAE including Callerya, DERRIS and MILLETTIA.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.Telomerase: An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.Papillomavirus Infections: Neoplasms of the skin and mucous membranes caused by papillomaviruses. They are usually benign but some have a high risk for malignant progression.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.CDC2-CDC28 Kinases: 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.Skin Neoplasms: Tumors or cancer of the SKIN.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Mice, Inbred C57BLE2F1 Transcription Factor: An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Neoplasms, Squamous Cell: Neoplasms of the SQUAMOUS EPITHELIAL CELLS. The concept does not refer to neoplasms located in tissue composed of squamous elements.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Electrowetting: Reducing the SURFACE TENSION at a liquid/solid interface by the application of an electric current across the interface thereby enhancing the WETTABILITY of the surface.ras Proteins: Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.
Both p16INK4a and p14ARF are involved in cell cycle regulation. p14ARF inhibits mdm2, thus promoting p53, which promotes p21 ... It is located near the genes for the tandem repeats INK4a and INK4b, which are 16 kDa (p16INK4a) and 15 kDa (p15INK4b) proteins ... July 1995). "A novel p16INK4A transcript". Cancer Res. 55 (14): 2995-7. PMID 7541708. Quelle DE, Zindy F, Ashmun RA, Sherr CJ ( ... January 2000). "Hypermethylation-associated inactivation of p14(ARF) is independent of p16(INK4a) methylation and p53 ...
It represses p19Arf and p16Ink4a. Bmi-1-/- neural stem cells and HSCs have high expression level of p19Arf and p16Ink4a which ... promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and ...
Concentrations of p16INK4a increase dramatically as tissue ages. p16INK4a, along with senescence-associated beta-galactosidase ... p16Ink4A is named after its molecular weight and its role in inhibiting CDK4. p16 is also known as: p16Ink4A p16Ink4 Cyclin- ... Therefore, p16INK4a could potentially be used as a blood test that measures how fast the body's tissues are aging at a ... Liu Y, Sanoff HK, Cho H, Burd CE, Torrice C, Ibrahim JG, Thomas NE, Sharpless NE (August 2009). "Expression of p16(INK4a) in ...
"Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders". Nature. 479: 232-6. doi:10.1038/nature10600 ...
The correlation between chronological age and expression levels of p16INK4a in T cells is r=0.56. p16INK4a expression levels ... Wang, Y; Zang, X; Wang, Y; Chen, P (2012). "High expression of p16INK4a and low expression of Bmi1 are associated with ... Baker, DJ (2011). "Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders". Nature. 479 (7372): 232- ... p16INK4a expression levels (also known as INK4a/ARF locus), and c) microsatellite mutations. The correlation between ...
Polycomb Bmi1 is known to regulate ink4 locus (p16Ink4a, p19Arf). Regulation of Polycomb-group proteins at bivalent chromatin ... promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and ...
In 2011, Sharpless and his team, using conditional p16INK4a knock-out mouse models, discovered that p16INK4a plays lineage- ... He has published numerous papers that show the role of p16INK4a in shutting down the stem cells that renew the body's various ... Liu, Y., Sanoff, H. K., Cho, H., Burd, C. E., Torrice, C., Ibrahim, J. G., … Sharpless, N. E. (2009). Expression of p16INK4a in ... Use of this system revealed the activation of p16INK4a in tissues surrounding nascent tumors, allowing scientists to non- ...
"p16(INK4a) translation suppressed by miR-24". PLoS ONE. 3 (3): e1864. doi:10.1371/journal.pone.0001864. PMC 2274865 . PMID ... suggested that miR-24 suppresses the tumor suppressor p16(INK4a). Lal et al. reported that mi-24 inhibits cell proliferation by ...
... to p16INK4a by preventing methylation of the p16INK4a promoter. Therefore, c-jun can prevent silencing of the gene p16INK4a. ... p16INK4a is a tumor suppressor and a cell cycle inhibitor, and a study shows that c-jun acts as "bodyguard" ... Kollmann K, Heller G, Sexl V (May 2011). "c-JUN prevents methylation of p16(INK4a) (and Cdk6): the villain turned bodyguard". ...
p16Ink4a and p19Arf expression are inhibited by Hmga2-dependent chromatin regulation. Many young adult stem cells are quiescent ... These mechanisms are regulated by p16Ink4a-CDK4/6-Rb and p19Arf-p53-P21Cip1 signaling pathways. Embryonic stem cells have ... In old adult stem cells, let-7 microRNA expression increases, reducing Hmga2 levels and increasing p16Ink4a and p19Arf levels. ... "Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf Expression". Cell. 135 ( ...
Jiang H, Chou HS, Zhu L (1998). "Requirement of cyclin E-cdk2 inhibition in p16INK4a-mediated growth suppression". Molecular ...
Yarbrough WG, Buckmire RA, Bessho M, Liu ET (Sep 1999). "Biologic and biochemical analyses of p16(INK4a) mutations from primary ... "Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a". Nature. 395 (6699): 237 ... "Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a". Nature. 395 (6699): 237 ...
"The induction of H3K9 methylation by PIWIL4 at the p16Ink4a locus". Biochem. Biophys. Res. Commun. 359 (3): 497-502. doi: ...
p16INK4a silencing in geriatric satellite cells restores quiescence and muscle regenerative functions. Myogenic progenitors for ... caused by derepression of p16INK4a (also called Cdkn2a). On injury, these cells fail to activate and expand, even in a youthful ...
2007). "The induction of H3K9 methylation by PIWIL4 at the p16Ink4a locus". Biochem. Biophys. Res. Commun. 359 (3): 497-502. ...
CDKN2A; ARF; CDK4I; CDKN2; CMM2; INK4; INK4A; MLM; MTS-1; MTS1; P14; P14ARF; P16; P16-INK4A; P16INK4; P16INK4A; P19; P19ARF; ...
"Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence". Nature. 409 (6823): 1067-70. doi: ... "Id-1 stimulates serum independent prostate cancer cell proliferation through inactivation of p16(INK4a)/pRB pathway". ...
The gene codes for two proteins, including the INK4 family member p16 (or p16INK4a) and p14arf. Both act as tumor suppressors ... Qureshi MA, Jan N, Dar NA, Hussain M, Andrabi KI (September 2012). "A novel p16(INK4A) mutation associated with esophageal ... Witkiewicz AK, Knudsen KE, Dicker AP, Knudsen ES (August 2011). "The meaning of p16(ink4a) expression in tumors: functional ... p16(INK4a) and p53 in basal cell carcinoma". The British Journal of Dermatology. 160 (6): 1215-21. doi:10.1111/j.1365-2133.2009 ...
Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be ... 1995). "A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma". Science. 269 (5228): 1281- ... 1996). "Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma". Nat. Genet. 12 (1): 97-9. doi:10.1038/ ... which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16INK4a. This kinase was shown to be ...
ADIS is maintained through the up-regulation of the cell cycle regulator p16ink4a. Pernicová, Z; Slabáková, E; Kharaishvili, G ...
2004). "Inverse correlation between p16INK4A expression and NF-kappaB activation in melanoma progression". Hum. Pathol. 35 (8 ...
"Mitogenic signalling and the p16INK4a-Rb pathway cooperate to enforce irreversible cellular senescence". Nature Cell Biology. 8 ...
"Epstein-Barr virus LMP1 blocks p16INK4a-RB pathway by promoting nuclear export of E2F4/5". The Journal of Cell Biology. 162 (2 ...
The homeoprotein SIX1 controls cellular senescence through the regulation of p16INK4A and differentiation-related genes. ...
... p16(INK4a)) and ATM promoter methylation in patients with impalpable breast lesions". Hum. Pathol. 46 (10): 1540-7. doi:10.1016 ...
p16INK4a is part of a cell-cycle regulatory pathway that converges in the tumor suppressor protein Rb. The mechanisms that ... The p16INK4a gene is frequently inactivated in human tumors, and inheritance of mutant alleles results in susceptibility to ... The tumor suppressor protein p16INK4a.. Serrano M1.. Author information. 1. Department of Immunology and Oncology, Centro ... The tumor suppressor protein p16INK4a (inhibitor of CDK4) is one of the most direct links between cell-cycle control and cancer ...
Transgenic mice with an additional copy of the p16INK4agene (in which young mice expressed p16INK4a to an extent comparable to ... was enhanced in HSCs from mice lacking p16INK4a and decreased in HSCs from mice overexpressing p16INK4a. Molofsky et al. ... found that p16INK4a mRNA expression increased in the bone marrow-derived hematopoietic stem cells (HSCs) of older mice. Older ... J. Krishnamurthy, M. R. Ramsey, K. L. Ligon, C. Torrice, A. Koh, S. Bonner-Weir, N. E. Sharpless, p16INK4a induces an age- ...
Rabbit polyclonal CDKN2A/p16INK4a antibody. Validated in WB, IP, IHC, ICC/IF and tested in Human. Cited in 3 publication(s). ... This product Rabbit Anti-CDKN2A/p16INK4a antibody (ab189302) IHC-P, ICC/IF, IP, WB ... Isoform 1 also known as: p16INK4a; Isoform 3 also known as: p12; Isoform 4 also known as: p14ARF; p19ARF; ARF. ... Recombinant fragment corresponding to Human CDKN2A/p16INK4a aa 8-156. (NP_000068.1).. Sequence: ...
p16Ink4a. promoter in mice in vivo. Engineered p16Ink4a. promoter hypermethylation led to transcriptional suppression in ... p16Ink4a. mutation in one allele and a somatic epimutation in the other had accelerated tumor onset and substantially shortened ... p16Ink4a. epimutation drives tumor formation and malignant progression and validate a targeted methylation approach to ...
p16INK4a. , which rises dynamically with aging and correlates with age-associated disease. Activation of p16INK4a. was ... p16INK4a. -mediated senescence. This work provides a toxicological platform to study mammalian aging and suggests agents that ... p16INK4a. expression, whereas arsenic modestly augmented, and cigarette smoke and UV light potently augmented, activation of ...
P16INK4a explanation free. What is P16INK4a? Meaning of P16INK4a medical term. What does P16INK4a mean? ... Looking for online definition of P16INK4a in the Medical Dictionary? ... P16INK4a , definition of P16INK4a by Medical dictionary https://medical-dictionary.thefreedictionary.com/P16INK4a ... redirected from P16INK4a). Also found in: Wikipedia. CDKN2A. A gene on chromosome 9p21 that encodes an alternate open reading ...
References for Abcams Human CDKN2A/p16INK4a peptide (ab105631). Please let us know if you have used this product in your ...
P16INK4a overexpression and survival in osteosarcoma patients: a meta analysis.. Bu J1, Li H1, Liu LH1, Ouyang YR1, Guo HB1, Li ... To elucidate whether p16(INK4a) is indeed a prognostic factor of osteosarcoma, we conducted a meta-analysis of the published ... In conclusion, the results from this meta-analysis highlight that p16(INK4a) is an effective biomarker of survival in patients ... Comments on the article of Bu, et al entitled "P16INK4a overexpression and survival in osteosarcoma patients: a meta analysis". ...
... p16INK4A and p19ARF, and is frequently inactivated in human cancers. The unusual structure of this locus has lead to ambiguity ... p16INK4A and p19ARF act in overlapping pathways in cellular immortalization Nat Cell Biol. 2000 Mar;2(3):148-55. doi: 10.1038/ ... The INK4A locus encodes two independent but overlapping genes, p16INK4A and p19ARF, and is frequently inactivated in human ... In immortal derivatives of cell lines expressing antisense p16INK4A or p19ARF RNA, growth arrest induced by recovery of ...
... p16 Ink4a +/− ; 3, p53 lox/lox ;p16 Ink4a −/− ; 4, p53 lox/+ ;p16 Ink4a +/− ; 5, p16 Ink4a/p19 Arf lox/+ ; 6, p16INK4A/p19 Arf ... B) PCR analysis of p16INK4A /p19Arf alleles in tumor cell lines from p16Ink4a /p19 Arf lox/+ mice shows only the recombined p16 ... Molecular analyses of PDAC cell lines from p16Ink4a /p19Arf lox/+ and p16INK4A/p19 Arf+/+ mice. (A) Western blot analysis p16 ... In addition, a subset of mice from both the p16Ink4a /p19Arf lox /+ and p53lox /+ p16Ink4a +/− colonies developed progressive ...
Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. David A ... Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts ... Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts ... Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts ...
... refinement of p16INK4A structure and determination of p15INK4B structure by comparative modeling and NMR data. ... 0.2-0.4 MM P16INK4A U-15N,13C; 4 MM HEPES, 1 MM DTT, 5 UM EDTA; 95% H2O, 5% D2O. ... 0.2-0.4 MM P16INK4A U-15N; 4 MM HEPES, 1 MM DTT, 5 UM EDTA; 95% H2O, 5% D2O. ... 0.2-0.4 MM P16INK4A; 4 MM HEPES, 1 MM DTT, 5 UM EDTA; 95% H2O, 5% D2O. ...
... refinement of p16INK4A structure and determination of p15INK4B structure by comparative modeling and NMR data. ... CYCLIN-DEPENDENT KINASE 4 INHIBITOR A (P16INK4A) A 156 Homo sapiens Gene Name(s): CDKN2A Gene View CDKN2 MTS1 ... SOLUTION NMR STRUCTURE OF TUMOR SUPPRESSOR P16INK4A, 20 STRUCTURES. *DOI: 10.2210/pdb1dc2/pdb ...
Tumor suppressor p16INK4A: determination of solution structure and analyses of its interaction with cyclin-dependent kinase 4. ... TUMOR SUPPRESSOR P16INK4A A 156 Homo sapiens Details: TUMOR SUPPRESSOR P16INK4A Gene Name(s): CDKN2A Gene View CDKN2 MTS1 ... SOLUTION NMR STRUCTURE OF TUMOR SUPPRESSOR P16INK4A, 18 STRUCTURES. *DOI: 10.2210/pdb1a5e/pdb ...
By using a panel of PCR-based methods, we have examined the status of the p16INK4a, ARF and p53 genes in 123 cases of non- ... By contrast, the 5-year survival was only 7% for cases with concurrent disruption of p16INK4a and the ARF-p53 pathway vs 38% ... For the aggressive lymphomas, the Kaplan-Meier estimate of overall survival for cases with disruption of either p16INK4a or the ... concurrent disruption of p16INK4a and the ARF-p53 pathway was an independent negative prognostic factor in NHL with aggressive ...
... Br J Haematol. 1997 Oct; ... p16INK4A, p21CIP1 and p27KIP1 by RT-PCR and immunohistochemistry. In vitro survival of these myeloma cells was examined by flow ...
Our results indicated that the frequency of P16INK4a methylation in cancer tissues was significantly higher than normal tissues ... However, the role of P16INK4a methylation in ovarian cancer still remains controversial. Therefore, we performed a meta- ... In conclusion, the present meta-analysis suggests that P16INK4a promoter methylation may be useful in distinguishing malignant ... Additionally, survival analysis showed that patients with P16INK4a promoter methylation had a shorter progression-free survival ...
p16(INK4A) induces senescence and inhibits EMT through microRNA-141/microRNA-146b-5p-dependent repression of AUF1 ,Al-Khalaf, ... p16INK4A(CDKN2A) (NM_000077) Human Tagged ORF Clone. CAT#: RC220937L2. Lenti ORF clone of Human cyclin-dependent kinase ... ARF; CDK4I; CDKN2; CMM2; INK4; INK4A; MLM; MTS-1; MTS1; P14; P14ARF; P16; P16-INK4A; P16INK4. ...
... which encodes p16INK4a and p14ARF (19). In addition, immunohistochemical analysis has shown overexpression of p16INK4a in oral ... Frequent Alterations of p16INK4a and p14ARF in Oral Proliferative Verrucous Leukoplakia. Laura A. Kresty, Susan R. Mallery, ... The p16INK4a and p14ARF genes were processed as reported previously (17). Briefly, PCR was employed with HPRT, an internal ... p16INK4a and p14ARF Homozygous Deletion. INK4a/ARF inactivation events in patients with PVL are summarized in Table 2. ...
p16Ink4a down-regulation leads to an activation of PKA-CREB-PGC1α signalling through increased phosphorylation of PKA ... The CDKN2A/B locus contains genes encoding cell cycle inhibitors, including p16Ink4a, which have not yet been implicated in the ... Cdkn2a/p16Ink4a regulates fasting-induced hepatic gluconeogenesis through the PKA-CREB-PGC1α pathway. ... Here we show that p16Ink4a-deficiency enhances fasting-induced hepatic glucose production in vivo by increasing the expression ...
Mao, L., Merlo, A., Bedi, G., Shapiro, G.I., Edwards, C.D., Rollins, B.J. & Sidransky, D. (1995) A novel p16INK4A transcript. ... Urashima, M., DeCaprio, J.A., Chauhan, D., Teoh, G., Ogata, A., Treon, S.P., Hoshi, & Anderson, K.C. (1997) p16 (INK4A) ... Shapiro, G.I., Edwards, C.D., Ewen, M.E. & Rollins, B.J. (1998) p16INK4A participates in a G1 arrest checkpoint in response to ... Zhou, M., Gu, L., Yeager, A.M. & Findley, H.W. (1997) Incidence and clinical significance of CDKN2/MTS1/p16ink4A and MTS2/ ...
... p16INK4a, p18INK4c, and p19INK4d; Refs. 1 and 3 ). The p16INK4a gene was implicated as a tumor suppressor gene by its frequent ... p16INK4a. Aberrant methylation of p16INK4a was assessed in the same samples analyzed for p14ARF methylation and demonstrated in ... D, MSP of p14ARF in primary colorectal carcinomas (CRC) of p14ARF (top panel) and p16INK4a (bottom panel). CRC1 and CRC6 are ... 2B ⇓ ). In 26 of 110 (24%) of the cases, p16INK4a was methylated without p14ARF methylation (Fig. 2B ⇓ ). Thus, methylation at ...
Pseudotype Virus-Like Particles Harbouring Inserted Target Antigen to Generate Antibodies against Cellular Marker p16INK4A. ... Pseudotype Virus-Like Particles Harbouring Inserted Target Antigen to Generate Antibodies against Cellular Marker p16INK4A," ...
p16INK4a is also suggested to play a role in controlling cell proliferation and apoptosis during mammary gland development. p16 ... Thus, p16-INK4a functions as a tumor suppressor in a variety of cells. Mutations in the CDKN2A gene are often found in many ... Anti-Human p16INK4a (1H4) Mouse IgG MoAb. The human cyclin-dependent kinase inhibitor 2A (CDKN2A) gene generates several ... This product is an affinity-purified IgG antibody that recognizes human p16-INK4a protein. The antibody was raised in mouse ...
p16(Ink4a) is a protein involved in regulation of the cell cycle. Currently, p16(Ink4a) is considered a tumor suppressor ... This review attempts to elucidate when and why p16(Ink4a) overexpression occurs, and to suggest possible implications of p16( ... p16(Ink4a) overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors.. [C Romagosa, S ... Intriguingly, overexpression of p16(Ink4a) has also been described in several tumors. ...
  • Senescence is often associated with DNA Damage foci and it involves the cell cycle inhibitors p21WAF and P16INK4A together with other proteins, including senescence-associated b Galactosidases (SAbGal) and several cytokines. (thefreedictionary.com)
  • The p16INK4a cyclin-dependent kinase inhibitor is implicated in replicative senescence, the state of permanent growth arrest provoked by cumulative cell divisions or as a response to constitutive Ras-Raf-MEK signalling in somatic cells. (openrepository.com)
  • Some contribution to senescence presumably underlies the importance of p16INK4a as a tumour suppressor but the mechanisms regulating its expression in these different contexts remain unknown. (openrepository.com)
  • Since this process is recognized as an evolutionarily conserved mechanism from yeast to mammalian cells, we compared the senescence-associated genetic alterations in the p53, p16INK4a, and telomere regulatory pathways using replicative senescent human, mouse, and chicken fibroblast cells. (elsevier.com)
  • Taken together, the present study demonstrates that the p53, p16INK4a, and telomere regulatory functions may be differentially regulated during replicative senescence in human, mouse, and chicken fibroblast cells. (elsevier.com)
  • p16INK4A G23D mutant shows a reduced ability to bind to CDK4 and prevent CDK4-mediated phosphorylation of RB1 (Scaini et al. (reactome.org)
  • The researchers are determining structure-function relationships of overlapping peptides derived from p16INK4a that inhibit the activity of CDK4/6 and identifying stabilized peptides that inhibit CDK4/6. (umn.edu)
  • The pharmacophore(s) of mutated peptides from p16INK4a will be assessed via time-resolved fluorescent resonance energy transfer assays and nuclear magnetic resonance spectroscopy to elucidate which residues are important to bind CDK4 and/or CDK6. (umn.edu)
  • p16INK4a induces a profound decrease in the CDK4/6-mediated pRb phosphorylation on Ser-807/811, a downregulation of CDK2 and CDK1 protein expression independently of G1 accumulation, and a decrease in Thr/Pro phosphorylation in part carried out by CDKs. (archives-ouvertes.fr)
  • p14 ARF, p15INK4b and p53 presented high expression levels, whereas p16INK4a exhibited low mRNA levels compared with the corresponding normal tissue. (euc.ac.cy)
  • It is located near the genes for the tandem repeats INK4a and INK4b, which are 16 kDa (p16INK4a) and 15 kDa (p15INK4b) proteins, respectively. (wikipedia.org)
  • The aim of this study was to evaluate the relationships between HPV DNA presence and p16INK4a, p21waf1/cip1, p53 and cyclin D1 immunoexpression in heterogenous HPV-positive and HPV-negative groups of laryngeal cancers and inverted papillomas. (viamedica.pl)
  • The increased immunoexpression of p16INK4a and cyclin D1, and the lower immunoexpression of p21waf1/cip1 and p53 in the HPV-positive group compared to the HPV-negative group, supports the hypothesis that HPV may play an important role in cell cycle dysregulation. (viamedica.pl)
  • HPV DNA, E6/E7 mRNA, and p16INK4a detection in head and neck cancers: a systematic review and meta-analysis. (sciensano.be)
  • Conclusão - Ocorre perda da expressão imunoistoquímica da proteína p16INK4a, corroborando as informações de que a inativação do gene p16 é um evento frequente e que pode exercer papel importante na carcinogênese do adenocarcinoma de esôfago. (ufrgs.br)
  • Although germline mutations in the coding region of the p16INK4A gene have been detected in some families with inherited melanoma, many other families show no evidence of such mutations and hence the role of p16INK4A in the development of this tumor is still unclear. (elsevier.com)
  • In this report, we describe a family with inherited melanoma in which a novel mutation in exon 2 of the p16INK4A gene segregates with the disease. (elsevier.com)
  • We conclude that family members carrying this germline mutation in the p16INK4A gene are predisposed to melanoma. (elsevier.com)
  • By extension, these findings implicate the p16INK4A gene in the development of some cases of familial melanoma. (elsevier.com)
  • Inhibition of p16INK4a may ameliorate the physiological impact of ageing on stem cells and thereby improve injury repair in aged tissue. (scaddenlab.com)
  • Here, we report that additional nullizygosity for p16Ink4a increases the frequency of meningioma and meningothelial proliferation in these mice without modifying the tumor grade. (harvard.edu)
  • However, the correlation between p16INK4a and miR-146b-5p in OS proliferation remains largely unknown. (portlandpress.com)
  • p16INK4a is also suggested to play a role in controlling cell proliferation and apoptosis during mammary gland development. (takarabio.com)
  • Notably, in the absence of p16INK4a, HSC repopulating defects and apoptosis were mitigated, improving the stress tolerance of cells and the survival of animals in successive transplants, a stem-cell-autonomous tissue regeneration model. (scaddenlab.com)