Genomes and Genes
Gene Symbol: Cdkn2a
Description: cyclin-dependent kinase inhibitor 2A
Alias: ARF-INK4a, Arf, INK4a-ARF, Ink4a/Arf, MTS1, Pctr1, p16, p16(INK4a), p16INK4a, p19
Publications186 found, 100 shown here
- KrasG12D-induced IKK2/β/NF-κB activation by IL-1α and p62 feedforward loops is required for development of pancreatic ductal adenocarcinomaJianhua Ling
Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Centre, Houston, 77030, USA
Cancer Cell 21:105-20. 2012..IKK2/β inactivation inhibited NF-κB activation and PDAC development in Kras(G12D) and Kras(G12D);Ink4a/Arf(F/F) mice, demonstrating a mechanistic link between IKK2/β and Kras(G12D) in PDAC inception...
- Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cellsIn Kyung Park
Division of Hematology Oncology, Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
Nature 423:302-5. 2003..cell associated genes, cell survival genes, transcription factors, and genes modulating proliferation including p16Ink4a and p19Arf was altered in bone marrow cells of the Bmi-1-/- mice...
- Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2T Kamijo
Howard Hughes Medical Institute, St Jude Children s Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
Proc Natl Acad Sci U S A 95:8292-7. 1998The INK4a-ARF locus encodes two proteins, p16(INK4a) and p19(ARF), that restrain cell growth by affecting the functions of the retinoblastoma protein and p53, respectively...
- Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4aM Serrano
Cold Spring Harbor Laboratory, New York 11724, USA
Cell 88:593-602. 1997..primary cells by ras requires either a cooperating oncogene or the inactivation of tumor suppressors such as p53 or p16. Here we show that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest...
- p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophagesCéline Cudejko
Universite Lille Nord de France, Lille, France
Blood 118:2556-66. 2011The CDKN2A locus, which contains the tumor suppressor gene p16(INK4a), is associated with an increased risk of age-related inflammatory diseases, such as cardiovascular disease and type 2 diabetes, in which macrophages play a crucial role...
- Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrestD E Quelle
Howard Hughes Medical Institute, St Jude Children s Research Hospital, Memphis, Tennessee 38101, USA
Cell 83:993-1000. 1995..An unrelated protein (p19ARF) arises in major part from an alternative reading frame of the mouse INK4a gene, and its ectopic expression in the nucleus of rodent fibroblasts induces G1 and ..
- Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesisC M Eischen
Department of Biochemistry, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
Genes Dev 13:2658-69. 1999..In cultured primary mouse embryo fibroblasts, c-Myc activates the p19(ARF)-Mdm2-p53 tumor suppressor pathway, enhancing p53-dependent apoptosis but ultimately selecting for surviving ..
- The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosisBarbara Herkert
Theodor Boveri Institute and 2 Rudolf Virchow Center, University of Wurzburg, D 97070 Wurzburg, Germany
J Cell Biol 188:905-18. 2010Oncogenic stress induces expression of the alternate reading frame (Arf) tumor suppressor protein. Arf then stabilizes p53, which leads to cell cycle arrest or apoptosis...
- SPARC promotes pericyte recruitment via inhibition of endoglin-dependent TGF-β1 activityLee B Rivera
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
J Cell Biol 193:1305-19. 2011..These results demonstrate that SPARC promotes pericyte migration by diminishing TGF-β activity and identify a novel function for endoglin in controlling pericyte behavior...
- Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progressionElena I Fomchenko
Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
PLoS ONE 6:e20605. 2011..Glioma progression is associated with elevated growth factor signaling and loss of function of tumor suppressors Ink4a, Arf and Pten. Yet, gliomas are cellularly heterogeneous; they recruit and trap normal cells during infiltration.
- Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4aViktor Janzen
Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Nature 443:421-6. 2006..Here we report that the cyclin-dependent kinase inhibitor p16INK4a, the level of which was previously noted to increase in other cell types with age, accumulates and modulates ..
- Bmi-1 over-expression in neural stem/progenitor cells increases proliferation and neurogenesis in culture but has little effect on these functions in vivoShenghui He
Howard Hughes Medical Institute, Department of Internal Medicine, Center for Stem Cell Biology, University of Michigan, 5435 Life Sciences Institute, 210 Washtenaw Ave, Ann Arbor, MI 48109 2216, USA
Dev Biol 328:257-72. 2009..pronounced effects of Bmi-1 over-expression in culture were largely attributable to the attenuated induction of p16(Ink4a) and p19(Arf) in culture, proteins that are generally not expressed by neural stem/progenitor cells in young ..
- Conditional ablation of Ikkb inhibits melanoma tumor development in miceJinming Yang
Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
J Clin Invest 120:2563-74. 2010..manner in mice null for the gene encoding the tumor suppressor inhibitor cyclin-dependent kinase 4/alternative reading frame (Ink4a/Arf)...
- mTORC1 signaling under hypoxic conditions is controlled by ATM-dependent phosphorylation of HIF-1αHakan Cam
Center for Childhood Cancer, Nationwide Children s Hospital, Columbus, OH 43205, USA
Mol Cell 40:509-20. 2010..Deregulation of these pathways in pediatric solid tumor xenografts suggests a link between mTORC1 dysregulation and solid tumor development and points to an important role for hypoxic regulation of mTORC1 activity in tumor development...
- Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARFT Kamijo
Howard Hughes Medical Institute, Department of Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
Cell 91:649-59. 1997..tumor suppressor locus encodes p16INK4a, an inhibitor of cyclin D-dependent kinases, and p19ARF, an alternative reading frame protein that also blocks cell proliferation...
- Oncogenic Braf induces melanocyte senescence and melanoma in miceNathalie Dhomen
Signal Transduction Team, Cancer Research UK Centre for Cell and Molecular Biology, The Institute of Cancer Research, London, UK
Cancer Cell 15:294-303. 2009..We show that the tumor suppressor p16(INK4a) is not required to induce melanocyte senescence and that its loss is not required for tumor progression, ..
- The tumor suppressor p16Ink4a regulates T lymphocyte survivalT Bianchi
Ludwig Institute for Cancer Research, Epalinges, Switzerland
Oncogene 25:4110-5. 2006In contrast to other cell cycle inhibitors, the tumor suppressor p16Ink4a is not detectable or expressed at very low levels in embryonic and adult mouse tissues, and therefore it has often been considered as a specialized checkpoint ..
- Decreased Mdm2 expression inhibits tumor development induced by loss of ARFP Wang
Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, 68198, USA
Oncogene 25:3708-18. 2006The tumor suppressor p14/p19(ARF) regulates Mdm2, which is known for controlling the p53 tumor suppressor...
- Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageingAnna V Molofsky
Howard Hughes Medical Institute, Department of Internal Medicine, and Center for Stem Cell Biology, University of Michigan, Ann Arbor, Michigan 48109 2216, USA
Nature 443:448-52. 2006..These declines in progenitor frequency and function correlate with increased expression of p16INK4a, which encodes a cyclin-dependent kinase inhibitor linked to senescence...
- Cdkn2a is an atherosclerosis modifier locus that regulates monocyte/macrophage proliferationChao Ling Kuo
Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY, USA
Arterioscler Thromb Vasc Biol 31:2483-92. 2011Common genetic variants in a 58-kb region of chromosome 9p21, near the CDKN2A/CDKN2B tumor suppressor locus, are strongly associated with coronary artery disease. However, the underlying mechanism of action remains unknown.
- Cooperative effects of INK4a and ras in melanoma susceptibility in vivoL Chin
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
Genes Dev 11:2822-34. 1997The familial melanoma gene (INK4a/MTS1/CDKN2) encodes potent tumor suppressor activity. Although mice null for the ink4a homolog develop a cancer-prone condition, a pathogenetic link to melanoma susceptibility has yet to be established...
- An inducible mouse model of melanoma expressing a defined tumor antigenIvo J Huijbers
Ludwig Institute for Cancer Research and Cellular Genetics Unit, Universite Catholique de Louvain, Brussels, Belgium
Cancer Res 66:3278-86. 2006..melanocytes, we aimed at simultaneously activating the Ras pathway and inactivating tumor suppressor Ink4a/Arf, thereby reproducing two genetic events frequently observed in human melanoma. The melanomas are induced by s.c...
- Activated TNF-alpha/NF-kappaB signaling via down-regulation of Fas-associated factor 1 in asbestos-induced mesotheliomas from Arf knockout miceDeborah A Altomare
Human Genetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
Proc Natl Acad Sci U S A 106:3420-5. 2009..and p14(ARF) [mouse p19(Arf)], designated INK4A (inhibitor of cyclin dependent kinase 4) and ARF (alternative reading frame) here, that are translated from alternatively spliced mRNAs...
- Genetic analysis of Pten and Ink4a/Arf interactions in the suppression of tumorigenesis in miceMingjian James You
Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 99:1455-60. 2002Dual inactivation of PTEN and INK4a/ARF tumor suppressor genes is a common feature observed in a broad spectrum of human cancer types...
- Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1Atsushi Iwama
Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108 8639, Japan
Immunity 21:843-51. 2004..Our findings define Bmi-1 as a central player in HSC self-renewal and demonstrate that Bmi-1 is a target for therapeutic manipulation of HSCs...
- LKB1 modulates lung cancer differentiation and metastasisHongbin Ji
Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
Nature 448:807-10. 2007..Although Kras mutation cooperated with loss of p53 or Ink4a/Arf (also known as Cdkn2a) in this system, the strongest cooperation was seen with homozygous inactivation of Lkb1...
- Rescue of key features of the p63-null epithelial phenotype by inactivation of Ink4a and ArfXiaohua Su
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
EMBO J 28:1904-15. 2009..Here, we show that inactivation of p63 in mice is accompanied by aberrantly increased expression of the Ink4a and Arf tumour suppressor genes...
- Somatic integration of an oncogene-harboring Sleeping Beauty transposon models liver tumor development in the mouseCorey M Carlson
The Arnold and Mabel Beckman Center for Transposon Research, Institute of Human Genetics, Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA
Proc Natl Acad Sci U S A 102:17059-64. 2005..NRAS oncogene-driven tumors developed when such vectors were delivered to the livers of p19Arf-null or heterozygous mice...
- The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locusJ J Jacobs
Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam
Nature 397:164-8. 1999..In these fibroblasts and in bmi-1-deficient lymphocytes, the expression of the tumour suppressors p16 and p19Arf, which are encoded by ink4a, is raised markedly...
- INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53C A Schmitt
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
Genes Dev 13:2670-7. 1999The INK4a/ARF locus encodes upstream regulators of the retinoblastoma and p53 tumor suppressor gene products...
- The PTEN and INK4A/ARF tumor suppressors maintain myelolymphoid homeostasis and cooperate to constrain histiocytic sarcoma development in humansDaniel R Carrasco
Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
Cancer Cell 9:379-90. 2006..Here, genetic analysis of coincident loss of Pten and Ink4a/Arf tumor suppressors in the mouse revealed a neoplastic phenotype dominated by a premalignant expansion of ..
- ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in miceAl Charest
Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
Cancer Res 66:7473-81. 2006..rearrangement product of ROS (FIG-ROS) cooperates with loss of the tumor suppressor gene locus Ink4a;Arf to produce glioblastomas in the mouse...
- Ink4a/Arf tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouseChristine M Khoo
Department of Medical Oncology, Belfer Foundation Institute for Innovative Cancer Science, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 104:3931-6. 2007The Rb/p16(Ink4a) and p53/p19Arf tumor suppressor pathways have been linked to diverse cancer-relevant processes, including those governing the cellular responses to telomere dysfunction...
- Arf-induced turnover of the nucleolar nucleophosmin-associated SUMO-2/3 protease Senp3Mei Ling Kuo
Howard Hughes Medical Institute, Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
Cell Cycle 7:3378-87. 2008The stabilization and subcellular localization of the p19(Arf) tumor suppressor protein and the SUMO-2/3 deconjugating protease Senp3 each depend upon their binding to the abundant nucleolar protein nucleophosmin (Npm/B23)...
- Tumor spectrum in ARF-deficient miceT Kamijo
Howard Hughes Medical Institute, and Department of Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
Cancer Res 59:2217-22. 1999The p19ARF product of the INK4a/ARF locus is induced in response to potentially oncogenic hyperproliferative signals and activates p53 by interfering with its negative regulator, Mdm2...
- Loss of p16Ink4a confers susceptibility to metastatic melanoma in miceP Krimpenfort
Division of Molecular Genetics and Centre for Biomedical Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
Nature 413:83-6. 2001..However, because CDKN2A encodes two distinct cell cycle inhibitory proteins, p16INK4a and p14ARF (p19Arf in mice), the mechanism of tumour suppression by CDKN2A has remained controversial...
- Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformationNabeel Bardeesy
Department of Adult Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
Nature 419:162-7. 2002..this in vivo tumour suppressor function, Lkb1 deficiency prevents culture-induced senescence without loss of Ink4a/Arf or p53...
- AP-1 dimers regulate transcription of the p14/p19ARF tumor suppressor geneMaya Ameyar-Zazoua
Unit of Gene Expression and Disease, Department of Developmental Biology, Pasteur Institute, 25, rue du Docteur Roux, 75724 Paris Cedex 15, France
Oncogene 24:2298-306. 2005..The p14/p19ARF tumor suppressor gene is a key link between oncogenic Ras signaling and the p53 pathway...
- Overexpression of the cell cycle inhibitor p16INK4a promotes a prothrombotic phenotype following vascular injury in miceJessica C Cardenas
Department of Pathology and Laboratory Medicine, University of North Carolina Chapel Hill, NC 27599 7035, USA
Arterioscler Thromb Vasc Biol 31:827-33. 2011Age-associated cellular senescence is thought to promote vascular dysfunction. p16(INK4a) is a cell cycle inhibitor that promotes senescence and is upregulated during normal aging...
- PAX3-FOXO1 induces cannabinoid receptor 1 to enhance cell invasion and metastasisAmy D Marshall
Department of Genetics, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
Cancer Res 71:7471-80. 2011..Cnr1 loss by either route also dramatically reduced lung metastasis formation. Taken together, our findings strongly implicate Cnr1 as a novel tractable target to inhibit ARMS invasion and metastasis...
- Mdm2 regulates p53 independently of p19(ARF) in homeostatic tissuesKathleen A O'Leary
Department of Oncology, University of Wisconsin, Madison, Wisconsin 53706, USA
Mol Cell Biol 24:186-91. 2004..For example, the p19(ARF) tumor suppressor (p14(ARF) in humans) appears to stimulate the apoptotic function of the p53 tumor suppressor to ..
- Transient expression of the Arf tumor suppressor during male germ cell and eye development in Arf-Cre reporter miceAdam Gromley
Howard Hughes Medical Institute and Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
Proc Natl Acad Sci U S A 106:6285-90. 2009The Arf tumor suppressor is expressed transiently during mouse male germ cell and eye development...
- A novel zinc finger protein Zfp277 mediates transcriptional repression of the Ink4a/arf locus through polycomb repressive complex 1Masamitsu Negishi
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
PLoS ONE 5:e12373. 2010..group (PcG) proteins play a crucial role in cellular senescence as key transcriptional regulators of the Ink4a/Arf tumor suppressor gene locus...
- Bidirectional autoregulatory mechanism of metastasis-associated protein 1-alternative reading frame pathway in oncogenesisDa qiang Li
Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington, DC 20037, USA
Proc Natl Acad Sci U S A 108:8791-6. 2011..we report a previously unrecognized bidirectional autoregulatory loop between MTA1 and tumor suppressor alternative reading frame (ARF)...
- A KrasG12D-driven genetic mouse model of pancreatic cancer requires glypican-1 for efficient proliferation and angiogenesisC A Whipple
Department of Medicine, Dartmouth Medical School, Hanover, NH, USA
Oncogene 31:2535-44. 2012..pancreas-specific Cre-mediated activation of oncogenic Kras (Kras(G12D)) with deletion of a conditional INK4A/Arf allele (Pdx1-Cre;LSL-Kras(G12D);INK4A/Arf(lox/lox);GPC1(-/-) mice)...
- Activated STAT5 promotes long-lived cytotoxic CD8+ T cells that induce regression of autochthonous melanomaMagali Grange
Centre d immunologie de Marseille Luminy, Universite de la Mediterranee, UMR6546, INSERM UMR631, and CNRS UMR6102, Marseille, France
Cancer Res 72:76-87. 2012....
- Ink4a/Arf expression is a biomarker of agingJanakiraman Krishnamurthy
Department of Medicine, The Lineberger Comprehensive Cancer Center, The University of North Carolina School of Medicine, Chapel Hill, North Carolina, 27599 7295, USA
J Clin Invest 114:1299-307. 2004The Ink4a/Arf locus encodes 2 tumor suppressor molecules, p16INK4a and Arf, which are principal mediators of cellular senescence...
- Impaired processing of DNA photoproducts and ultraviolet hypermutability with loss of p16INK4a or p19ARFPapri Sarkar-Agrawal
Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA
J Natl Cancer Inst 96:1790-3. 2004..We transfected unirradiated mouse fibroblast cells with UV-treated DNA to measure DNA repair in normal, p16INK4a mutant, p19ARF mutant, or double mutant mouse host cells...
- Modeling INK4/ARF tumor suppression in the mouseJustin H Berger
Massachusetts General Hospital Cancer Center, Department of Medicine, Harvard Medical School, Boston, MA 02114, USA
Curr Mol Med 7:63-75. 2007The INK4/ARF locus encodes the p15(INK4B), p16(INK4A) and p14(ARF) tumor suppressor proteins whose loss of function is associated with the pathogenesis of many human cancers...
- Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasisMatthieu Lacroix
Institut de Genetique Moleculaire de Montpellier, UMR5535, Centre National de la Recherche Scientifique, 34293 Montpellier, France
Proc Natl Acad Sci U S A 107:21076-81. 2010..The clonogenic potential of E4F1 KO ESCs is rescued by Bmi1 overexpression or by Ink4a/Arf or p53 depletion...
- Expression of the p16INK4a tumor suppressor versus other INK4 family members during mouse development and agingF Zindy
Department of Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
Oncogene 15:203-11. 1997..Transcripts encoding the INK4a alternative reading frame product p19ARF were not detected before birth but were ubiquitous postnatally...
- Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesisN E Sharpless
Departments of Adult Oncology, Medicine and Genetics, Harvard Medical School and the Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
Nature 413:86-91. 2001The cyclin-dependent kinase inhibitor p16INK4a can induce senescence of human cells, and its loss by deletion, mutation or epigenetic silencing is among the most frequently observed molecular lesions in human cancer...
- Differential impact of Ink4a and Arf on hematopoietic stem cells and their bone marrow microenvironment in Bmi1-deficient miceHideyuki Oguro
Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Sciences, University of Tokyo, Tokyo 108 8679, Japan
J Exp Med 203:2247-53. 2006..In this study, we show that derepressed p16(Ink4a) and p19(Arf) in Bmi1-deficient mice were tightly associated with a loss of self-renewing HSCs...
- Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locusAlexandros Tzatsos
Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA
Proc Natl Acad Sci U S A 106:2641-6. 2009..that Ndy1 is down-regulated during senescence in mouse embryonic fibroblasts (MEFs) and that it represses the Ink4a/Arf locus...
- E1A signaling to p53 involves the p19(ARF) tumor suppressorE de Stanchina
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 USA
Genes Dev 12:2434-42. 1998..activates p53 through a signaling pathway involving the retinoblastoma protein and the tumor suppressor p19(ARF)...
- Prolonged activation of the mitogen-activated protein kinase pathway promotes DNA synthesis in primary hepatocytes from p21Cip-1/WAF1-null mice, but not in hepatocytes from p16INK4a-null miceK L Auer
Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA
Biochem J 336:551-60. 1998..DNA synthesis and increased expression of the cyclin-dependent kinase inhibitor (CKI) proteins p21Cip-1/WAF1 and p16INK4a. To evaluate the relative importance of these CKIs in mediating this response, we determined the impact of ..
- The Arf tumor suppressor gene promotes hyaloid vascular regression during mouse eye developmentRobyn N McKeller
Department of Hematology Oncology, Developmental Neurobiology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA
Proc Natl Acad Sci U S A 99:3848-53. 2002A key tumor suppressor mechanism that is disrupted frequently in human cancer involves the ARF and p53 genes...
- Genetic determinants of malignancy in a mouse model for oligodendrogliomaWilliam A Weiss
Department of Neurology, University of California, San Francisco, California 94143 0663, USA
Cancer Res 63:1589-95. 2003Oligodendrogliomas of all grades overexpress epidermal growth factor receptor (EGFR), whereas deletion of ink4a/arf is found only in high-grade tumors...
- Cooperativity of p19ARF, Mdm2, and p53 in murine tumorigenesisLynette Moore
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Oncogene 22:7831-7. 2003The p19ARF gene product responds to oncogenic stresses by interfering with the inhibitory effects of Mdm2 on p53, thus enhancing p53 activity and its antiproliferative functions...
- Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathwayDmitry V Bulavin
Gene Response Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Nat Genet 36:343-50. 2004..Disruption of the gene Cdkn2a (encoding p16 and p19), but not of Trp53 (encoding p53), reconstituted cell transformation in Ppm1d-null MEFs...
- Sumoylation induced by the Arf tumor suppressor: a p53-independent functionKenji Tago
Howard Hughes Medical Institute, St Jude Children s Research Hospital, Memphis, TN 38105, USA
Proc Natl Acad Sci U S A 102:7689-94. 2005The mouse p19(Arf) protein has both p53-dependent and p53-independent tumor-suppressive activities...
- Nucleophosmin is required for DNA integrity and p19Arf protein stabilityEmanuela Colombo
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
Mol Cell Biol 25:8874-86. 2005Nucleophosmin (NPM) is a nucleolar phosphoprotein that binds the tumor suppressors p53 and p19(Arf) and is thought to be indispensable for ribogenesis, cell proliferation, and survival after DNA damage...
- Oncogenic activity of Cdc6 through repression of the INK4/ARF locusSusana Gonzalez
Tumor Suppression Group, Spanish National Cancer Research Center CNIO, E 28029 Madrid, Spain
Nature 440:702-6. 2006The INK4/ARF locus encodes three tumour suppressors (p15(INK4b), ARF and p16(INK4a)) and is among the most frequently inactivated loci in human cancer...
- Polycomb complexes regulate cellular senescence by repression of ARF in cooperation with E2F3Jun Miki
Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano 390 8621, Japan
Genes Cells 12:1371-82. 2007..Mel18-null MEFs undergo typical premature senescence accompanied by the up-regulation of ARF/p53/p16(INK4a) and decrease of Ring1b/Bmi1...
- Differential p53-independent outcomes of p19(Arf) loss in oncogenesisZhenbang Chen
Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Harvard Medical School, Boston, MA 02115, USA
Sci Signal 2:ra44. 2009One reported function of the tumor suppressor p19(Arf) is to stabilize p53, providing a critical checkpoint in the response to oncogenic insults...
- ARF suppresses tumor angiogenesis through translational control of VEGFA mRNAHiroyuki Kawagishi
Department of Mechanism of Aging, National Center for Geriatrics and Gerontology, Aichi, Japan
Cancer Res 70:4749-58. 2010..Here, we report that the nucleolar tumor suppressor p19(ARF) suppresses VEGFA expression, acting at the level of mRNA translation without affecting the transcription of the ..
- Role of the INK4a locus in tumor suppression and cell mortalityM Serrano
Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York, 11724 USA
Cell 85:27-37. 1996The cell cycle inhibitor p16INK4a is inactivated in many human tumors and in families with hereditary melanoma and pancreatic cancer...
- Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16INK4a and p19ARF, is a candidate for the plasmacytoma susceptibility locus, Pctr1S Zhang
Laboratory of Genetics, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4255, USA
Proc Natl Acad Sci U S A 95:2429-34. 1998..Restriction fragment length polymorphisms between BALB/c and DBA/2 for Cdkn2a(p16) and Cdkn2b(p15), and between BALB/c and Mus spretus for Cdkn2c(p18(INK4c)) were used to position these loci ..
- The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53J Pomerantz
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
Cell 92:713-23. 1998The INK4a gene encodes two distinct growth inhibitors--the cyclin-dependent kinase inhibitor p16Ink4a, which is a component of the Rb pathway, and the tumor suppressor p19Arf, which has been functionally linked to p53...
- A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in miceE C Holland
Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Genes Dev 12:3675-85. 1998..These mutations are associated usually with deletions of the INK4a-ARF locus, which encodes two gene products (p16(INK4a) and p19(ARF)) involved in cell-cycle arrest and apoptosis...
- Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53R Honda
School of Life Science, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo 192 0392, Japan
EMBO J 18:22-7. 1999..We further investigated whether the tumor suppressor p19(ARF) affects the ubiquitin ligase activity of Mdm2 for p53...
- Essential role for oncogenic Ras in tumour maintenanceL Chin
Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
Nature 400:468-72. 1999..Our results provide genetic evidence that H-RasV12G is important in both the genesis and maintenance of solid tumours...
- Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patchedC Wetmore
Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
Cancer Res 61:513-6. 2001..in tumor incidence was observed in Ptc+/- mice carrying a mutation in APC (Min+/-) or in Ptc+/- mice deficient in p19ARF. Thus, there is a specific interaction between p53 loss and heterozygosity of Ptc that results in medulloblastoma...
- Mice doubly deficient for the Polycomb Group genes Mel18 and Bmi1 reveal synergy and requirement for maintenance but not initiation of Hox gene expressionT Akasaka
Department of Molecular Embryology, Graduate School of Medicine, Chiba University, Chuo Ku, Chiba 260 8670, Japan
Development 128:1587-97. 2001..Furthermore, we show an unexpected requirement for Mel18 and Bmi1 gene products to maintain stable expression of Hox cluster genes in regions caudal to the prospective anterior expression boundaries during subsequent development...
- A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapyClemens A Schmitt
Cold Spring Harbor Laboratory, 1 Bungtown Road, New York 11724, USA
Cell 109:335-46. 2002..that primary murine lymphomas also respond to chemotherapy by engaging a senescence program controlled by p53 and p16(INK4a)...
- Genome-wide retroviral insertional tagging of genes involved in cancer in Cdkn2a-deficient miceAnders H Lund
Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
Nat Genet 32:160-5. 2002..for loci that can participate in tumorigenesis in collaboration with loss of the Cdkn2a-encoded tumor suppressors p16INK4a and p19ARF...
- Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferationAnna V Molofsky
Howard Hughes Medical Institute, and Departments of Internal Medicine and Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109 0934, USA
Nature 425:962-7. 2003..In the absence of Bmi-1, the cyclin-dependent kinase inhibitor gene p16Ink4a is upregulated in neural stem cells, reducing the rate of proliferation...
- Arf tumor suppressor promoter monitors latent oncogenic signals in vivoFrederique Zindy
Departments of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA
Proc Natl Acad Sci U S A 100:15930-5. 2003..The Arf promoter was induced in several biologic settings previously shown to elicit mouse p19Arf expression...
- Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinomaAndrew J Aguirre
Department of Medical Oncology, Dana Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
Genes Dev 17:3112-26. 2003..pancreas-specific Cre-mediated activation of a mutant Kras allele (KrasG12D) and deletion of a conditional Ink4a/Arf tumor suppressor allele...
- Identification of candidate cancer-causing genes in mouse brain tumors by retroviral taggingFredrik K Johansson
Department of Genetics and Pathology, The Rudbeck Laboratory, University Hospital, SE 751 85 Uppsala, Sweden
Proc Natl Acad Sci U S A 101:11334-7. 2004..Our findings indicate that retroviral tagging with a growth factor-encoding virus may be a powerful means of identifying candidate tumor-causing genes in nonhematopoietic tumors...
- Disruption of E2F signaling suppresses the INK4a-induced proliferative defect in M33-deficient miceNathalie Coré
Centre d Immunologie INSERM CNRS, Case 906, 13288 Marseille Cedex 9, France
Oncogene 23:7660-8. 2004..cells have a senescent phenotype, associated to an abnormal accumulation of the cyclin-dependent kinase inhibitor p16INK4a protein...
- Loss of one allele of ARF rescues Mdm2 haploinsufficiency effects on apoptosis and lymphoma developmentChristine M Eischen
Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE 68198, USA
Oncogene 23:8931-40. 2004The tumor suppressor p19ARF inhibits Mdm2, which restricts the activity of p53. Complicated feedback and control mechanisms regulate ARF, Mdm2, and p53 interactions...
- Increased gene dosage of Ink4a/Arf results in cancer resistance and normal agingAnder Matheu
Spanish National Cancer Center CNIO, Madrid E 28029, Spain
Genes Dev 18:2736-46. 2004..We report here the characterization of a novel mouse model with increased activity for the Ink4a and Arf tumor suppressors...
- Cell type-specific tumor suppression by Ink4a and Arf in Kras-induced mouse gliomagenesisLene Uhrbom
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala, Sweden
Cancer Res 65:2065-9. 2005Homozygous deletion of the INK4a-ARF locus is one of the most frequent mutations found in human glioblastoma...
- Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in miceSunil R Hingorani
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Cancer Cell 7:469-83. 2005..These findings have clear implications for understanding mechanisms of disease pathogenesis, and for the development of detection and targeted treatment strategies...
- Metastasizing melanoma formation caused by expression of activated N-RasQ61K on an INK4a-deficient backgroundJulien Ackermann
ISREC, Swiss Institute for Experimental Cancer Research, National Center of Competence in Research Molecular Oncology, Epalinges, Switzerland
Cancer Res 65:4005-11. 2005..Consistent with the tumor suppressor function of the INK4a locus that encodes p16INK4A and p19(ARF), >90% of Tyr::N-RasQ61K INK4a-/- transgenic mice develop melanoma at 6 months...
- Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathwaysAnna V Molofsky
Howard Hughes Medical Institute, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109 0934, USA
Genes Dev 19:1432-7. 2005..partially rescued cerebellum development, demonstrating regional differences in the sensitivity of progenitors to p16Ink4a and p19Arf...
- mTOR promotes survival and astrocytic characteristics induced by Pten/AKT signaling in glioblastomaXiaoyi Hu
Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
Neoplasia 7:356-68. 2005....
- Arf-dependent regulation of Pdgf signaling in perivascular cells in the developing mouse eyeRicardo L A Silva
Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, TN, USA
EMBO J 24:2803-14. 2005..In cultured cells, p19Arf decreased Pdgfrbeta and blocked Pdgf-B-driven proliferation independently of Mdm2 and p53...
- ARF directly binds DP1: interaction with DP1 coincides with the G1 arrest function of ARFAbhishek Datta
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 900 S Ashland Ave, Chicago, IL 60607, USA
Mol Cell Biol 25:8024-36. 2005The tumor suppressor ARF inhibits cell growth in response to oncogenic stress in a p53-dependent manner...
- Role of genomic instability and p53 in AID-induced c-myc-Igh translocationsAlmudena R Ramiro
Laboratory of Molecular Immunology, The Rockefeller University, Universidad Autonoma de Madrid, Madrid 28049, Spain
Nature 440:105-9. 2006..In addition, translocations are inhibited by the tumour suppressors ATM, Nbs1, p19 (Arf) and p53, which is consistent with activation of DNA damage- and oncogenic stress-induced checkpoints during ..
- p16Ink4a or p19Arf loss contributes to Tal1-induced leukemogenesis in miceJ A Shank-Calvo
Department of Cancer Biology, University of Massachusetts Medical School, Worcester, 01650, USA
Oncogene 25:3023-31. 2006..of the INK4A/ARF locus in human T-ALL patients revealed frequent deletions in exon 2, the exon common to both p16(INK4A) and p14(ARF)...
- Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouseNabeel Bardeesy
Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 103:5947-52. 2006..In mouse models, Kras(G12D) initiates formation of premalignant pancreatic ductal lesions, and loss of either Ink4a/Arf (p16(Ink4a)/p19(Arf)) or p53 enables their malignant progression...
- Tumour biology: Policing of oncogene activity by p53Alejo Efeyan
Spanish National Cancer Centre CNIO, Madrid 28029, Spain
Nature 443:159. 2006
- A new mouse model to explore the initiation, progression, and therapy of BRAFV600E-induced lung tumorsDavid Dankort
Cancer Research Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco Comprehensive Cancer Center, California 94143, USA
Genes Dev 21:379-84. 2007..Consistent with Ink4a/Arf and TP53 tumor suppressor function, BRaf(VE) expression combined with mutation of either locus led to cancer ..
- The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cellsAdrian P Bracken
Centre for Epigenetics, Biotech Research and Innovation Centre BRIC, University of Copenhagen, Copenhagen 2200, Denmark
Genes Dev 21:525-30. 2007The p16INK4A and p14ARF proteins, encoded by the INK4A-ARF locus, are key regulators of cellular senescence, yet the mechanisms triggering their up-regulation are not well understood...
- Loss of Arf causes tumor progression of PDGFB-induced oligodendrogliomaE Tchougounova
Rudbeck Laboratory, Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden
Oncogene 26:6289-96. 2007..In high-grade gliomas, the subsequent loss of the INK4a-ARF locus is one of the most common mutations...
- ARF functions as a melanoma tumor suppressor by inducing p53-independent senescenceLinan Ha
Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, MD 20892 4264, USA
Proc Natl Acad Sci U S A 104:10968-73. 2007..in its advanced disseminated form, mutation/deletion of p53 is relatively rare, whereas its positive regulator ARF is often lost...
- A spatially and temporally restricted mouse model of soft tissue sarcomaDavid G Kirsch
Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
Nat Med 13:992-7. 2007..Deletion of the Ink4a-Arf locus (Cdkn2a), but not Bak1 and Bax, could substitute for mutation of Trp53 in this model...
- p15Ink4b is a critical tumour suppressor in the absence of p16Ink4aPaul Krimpenfort
Division of Molecular Genetics and Centre for Biomedical Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
Nature 448:943-6. 2007..p15INK4b encoded by CDKN2b, p16INK4a encoded by CDKN2a and p14ARF (p19Arf in mice) encoded by an alternative reading frame of CDKN2a (ref. 1)...
- A non-tumor suppressor role for basal p19ARF in maintaining nucleolar structure and functionAnthony J Apicelli
Department of Internal Medicine, Division of Molecular Oncology, Washington University School of Medicine, Campus Box 8069, 660 S Euclid Avenue, St Louis, MO 63110, USA
Mol Cell Biol 28:1068-80. 2008The nucleolus is the center of ribosome synthesis, with the nucleophosmin (NPM) and p19(ARF) proteins antagonizing one another to either promote or inhibit growth...
- Melanoma in p16INK4a and p19ARF Deficient MiceNORMAN SHARPLESS; Fiscal Year: 2006..The Ink4a/Arf locus, conserved in mouse and humans, encodes two distinct proteins, p16INK4a and p19ARF, both of which regulate critical tumor suppressor pathways, and each may play a substantive role in ..
- A flexible somatic and sporadic mouse model for pancreatic ductal adenocarcinomaBrian Lewis; Fiscal Year: 2007..Such an advance would benefit public health by reducing the mortality associated with this disease. [unreadable] [unreadable] [unreadable]..
- Molecular mediators of metastasis in hepatocellular carcinomaBrian C Lewis; Fiscal Year: 2010..findings, we propose to: 1) Explore whether the induction of metastasis is dependent on the loss of either the p16 or p19 tumor suppressor proteins (encoded by the Ink4a/Arf locus), or both...
- 500 MHz Wide Bore NMR SystemJason Koutcher; Fiscal Year: 2002..Thus this proposal, if funded , will support a very broad base of scientist and medical researchers in this area. ..
- 2003 Conference Pan-American Society Pigment Cell ReseaRuth Halaban; Fiscal Year: 2003..3. To provide partial support to students and junior faculty to attend the meeting. They request funds for the 2003 meeting as well as for the 2 subsequent PASPCR annual meetings in years 2004 and 2006. ..
- PROLIFERATION & MALIGNANT TRANSFORMATION OF MELANOCYTESRuth Halaban; Fiscal Year: 2004..evidence implicates contributions from at least two major processes to this aberrant behavior: a) loss of p16INK4a functional inhibition of cyclin dependent kinases 4 and 6 (CDK4/6); and b) aberrant expression of bFGF (basic ..
- Epigenetic Chromatin Changes as Melanoma MarkersRuth Halaban; Fiscal Year: 2006..Altogether, the results are likely to generate a novel marker(s) that can be used to assess propensity for malignant transformation, tumor progression and/or sensitivity to chemotherapeutic drugs that target chromatin conformation. ..
- Memorial Sloan Kettering Small Animal Imaging ResearchJason Koutcher; Fiscal Year: 2006..abstract_text> ..
- Optimizing Chemotherapy Dose Using 31P NMR SpectroscopyJason Koutcher; Fiscal Year: 2006..If measurements of 6PG in peripheral blood lymphocytes correlate with tumor 6PG, future studies would not require further NMR studies. [unreadable] [unreadable]..
- Dynamic Magnetic Resonance Imaging of Bone TumorsJason Koutcher; Fiscal Year: 2007..If successful, it will provide a tool to predict failure/response to chemotherapy, resulting in patient specific treatment which will likely enhance outcome. ..
- Cytocidal Therapy In Vivo for Drug-Resistant TumorsJason Koutcher; Fiscal Year: 2007..If validated clinically, the proposed therapy will open the way for cure of metastatic breast cancer, and the therapeutic strategy likely will apply to other drug-resistant types of cancer. ..
- 9.4T/20 cm MRI for Cancer ResearchJason Koutcher; Fiscal Year: 2007..unreadable] [unreadable] [unreadable]..
- Memorial Sloan Kettering Small Animal Imaging ResearchJason Koutcher; Fiscal Year: 2008..abstract_text> ..
- The Role of Mdm2 in Lymphoma DevelopmentCHRISTINE EISCHEN; Fiscal Year: 2007..Surprisingly, Mdm2 overexpression frequently occurred in lymphomas that had inactivated p53 or p19ARF, a regulator of Mdm2...
- MOLECULAR PATHOGENESIS OF MALIGNANT MELANOMALynda Chin; Fiscal Year: 2002..Specifically, I will focus on the differential roles of p15 INK4b, P16INK4a and p19ARF as well as activated H-rasva112 in development of malignant melanoma...
- Genomic & Genetic Characterization of Amplicons in GBMsLynda Chin; Fiscal Year: 2007..The highest potential candidate glioma oncogene will be further validated by rigorous in vivo transgenesis study. ..