Cdkn2a

Summary

Gene Symbol: Cdkn2a
Description: cyclin-dependent kinase inhibitor 2A
Alias: ARF-INK4a, Arf, INK4a-ARF, Ink4a/Arf, MTS1, Pctr1, p16, p16(INK4a), p16INK4a, p19, p19ARF, CDK4I, cyclin-dependent kinase 4 inhibitor A, cyclin-dependent kinase inhibitor 2A (p16, inhibits CDK4), cyclin-dependent kinase inhibitor 2A, isoforms 1/2, cyclin-dependent kinase inhibitor protein, mitochondrial smARF, p16-INK4, p16-INK4a
Species: mouse

Top Publications

  1. pmc KrasG12D-induced IKK2/β/NF-κB activation by IL-1α and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma
    Jianhua 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
  2. pmc The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence
    Karl Agger
    Biotech Research and Innovation Centre BRIC and Centre for Epigenetics, University of Copenhagen, DK 2200 Copenhagen, Denmark
    Genes Dev 23:1171-6. 2009
  3. ncbi Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice
    Sunil R Hingorani
    Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Cell 7:469-83. 2005
  4. ncbi Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells
    In Kyung Park
    Division of Hematology Oncology, Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
    Nature 423:302-5. 2003
  5. pmc Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation
    Anna 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
  6. pmc Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2
    T 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. 1998
  7. ncbi Role of the INK4a locus in tumor suppression and cell mortality
    M Serrano
    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York, 11724 USA
    Cell 85:27-37. 1996
  8. ncbi Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
    M Serrano
    Cold Spring Harbor Laboratory, New York 11724, USA
    Cell 88:593-602. 1997
  9. ncbi Loss of Arf causes tumor progression of PDGFB-induced oligodendroglioma
    E Tchougounova
    Rudbeck Laboratory, Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden
    Oncogene 26:6289-96. 2007
  10. pmc p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophages
    Céline Cudejko
    Universite Lille Nord de France, Lille, France
    Blood 118:2556-66. 2011

Scientific Experts

Detail Information

Publications159 found, 100 shown here

  1. pmc KrasG12D-induced IKK2/β/NF-κB activation by IL-1α and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma
    Jianhua 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...
  2. pmc The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence
    Karl Agger
    Biotech Research and Innovation Centre BRIC and Centre for Epigenetics, University of Copenhagen, DK 2200 Copenhagen, Denmark
    Genes Dev 23:1171-6. 2009
    The tumor suppressor proteins p16INK4A and p14ARF, encoded by the INK4A-ARF locus, are key regulators of cellular senescence...
  3. ncbi Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice
    Sunil 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...
  4. ncbi Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells
    In 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...
  5. pmc Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation
    Anna 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...
  6. pmc Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2
    T 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. 1998
    The 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...
  7. ncbi Role of the INK4a locus in tumor suppression and cell mortality
    M Serrano
    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York, 11724 USA
    Cell 85:27-37. 1996
    The cell cycle inhibitor p16INK4a is inactivated in many human tumors and in families with hereditary melanoma and pancreatic cancer...
  8. ncbi Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
    M 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...
  9. ncbi Loss of Arf causes tumor progression of PDGFB-induced oligodendroglioma
    E 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...
  10. pmc p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophages
    Céline Cudejko
    Universite Lille Nord de France, Lille, France
    Blood 118:2556-66. 2011
    The 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...
  11. pmc The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis
    Barbara Herkert
    Theodor Boveri Institute and 2 Rudolf Virchow Center, University of Wurzburg, D 97070 Wurzburg, Germany
    J Cell Biol 188:905-18. 2010
    Oncogenic stress induces expression of the alternate reading frame (Arf) tumor suppressor protein. Arf then stabilizes p53, which leads to cell cycle arrest or apoptosis...
  12. pmc Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression
    Elena 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.
  13. ncbi Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest
    D E Quelle
    Howard Hughes Medical Institute, St Jude Children s Research Hospital, Memphis, Tennessee 38101, USA
    Cell 83:993-1000. 1995
    The INK4a (MTS1, CDKN2) gene encodes an inhibitor (p16INK4a) of the cyclin D-dependent kinases CDK4 and CDK6 that blocks them from phosphorylating the retinoblastoma protein (pRB) and prevents exit from the G1 phase of the cell cycle...
  14. pmc Pancreatic cancer and precursor pancreatic intraepithelial neoplasia lesions are devoid of primary cilia
    E Scott Seeley
    Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03756, USA
    Cancer Res 69:422-30. 2009
    ..Thus, arrested ciliogenesis is a cardinal feature of PDAC and its precursor PanIN lesions, does not require ongoing proliferation, and could potentially be targeted pharmacologically...
  15. pmc SPARC promotes pericyte recruitment via inhibition of endoglin-dependent TGF-β1 activity
    Lee 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...
  16. pmc Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis
    C 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 ..
  17. ncbi Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a
    Viktor 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 ..
  18. doi Tumor-initiated inflammation overrides protective adaptive immunity in an induced melanoma model in mice
    Saïdi M Soudja
    Centre d immunologie de Marseille Luminy, Universite de la Mediterranee, Institut National de la Sante et de la Recherche Medicale, U631 Centre National de la Recherche Scientifique, UMR6102, Marseille, France
    Cancer Res 70:3515-25. 2010
    ..immune system on two differentially aggressive melanomas developing in mice on conditional deletion of the INK4A/ARF tumor suppressor gene, with concomitant expression of oncogene H-Ras(G12V) and a natural cancer-germline tumor ..
  19. ncbi A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy
    Clemens 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)...
  20. pmc Conditional ablation of Ikkb inhibits melanoma tumor development in mice
    Jinming Yang
    Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Clin Invest 120:2563-74. 2010
    ..for the gene encoding the tumor suppressor inhibitor cyclin-dependent kinase 4/alternative reading frame (Ink4a/Arf)...
  21. doi mTORC1 signaling under hypoxic conditions is controlled by ATM-dependent phosphorylation of HIF-1α
    Hakan 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...
  22. pmc Bmi-1 over-expression in neural stem/progenitor cells increases proliferation and neurogenesis in culture but has little effect on these functions in vivo
    Shenghui 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 ..
  23. ncbi The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53
    J Pomerantz
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Cell 92:713-23. 1998
    The 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...
  24. pmc ARF functions as a melanoma tumor suppressor by inducing p53-independent senescence
    Linan 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...
  25. doi Oncogenic Braf induces melanocyte senescence and melanoma in mice
    Nathalie 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, ..
  26. doi p19(ARF) deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis
    Herminia Gonzalez-Navarro
    Department of Molecular and Cellular Pathology and Therapy, Instituto de Biomedicina de Valencia, Spanish Council for Scientific Research, Valencia, Spain
    J Am Coll Cardiol 55:2258-68. 2010
    The goal of this study was to investigate the role in atherosclerosis of the tumor suppressor protein ARF (human p14(ARF), mouse p19(ARF)) encoded by the CDKN2A gene.
  27. ncbi Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF
    T 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
    The INK4a tumor suppressor locus encodes p16INK4a, an inhibitor of cyclin D-dependent kinases, and p19ARF, an alternative reading frame protein that also blocks cell proliferation...
  28. pmc Cdkn2a is an atherosclerosis modifier locus that regulates monocyte/macrophage proliferation
    Chao Ling Kuo
    Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY, USA
    Arterioscler Thromb Vasc Biol 31:2483-92. 2011
    Common 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.
  29. ncbi Decreased Mdm2 expression inhibits tumor development induced by loss of ARF
    P Wang
    Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, 68198, USA
    Oncogene 25:3708-18. 2006
    The tumor suppressor p14/p19(ARF) regulates Mdm2, which is known for controlling the p53 tumor suppressor...
  30. ncbi The tumor suppressor p16Ink4a regulates T lymphocyte survival
    T Bianchi
    Ludwig Institute for Cancer Research, Epalinges, Switzerland
    Oncogene 25:4110-5. 2006
    In 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 ..
  31. pmc Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing
    Anna 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...
  32. ncbi An inducible mouse model of melanoma expressing a defined tumor antigen
    Ivo 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...
  33. pmc Cooperative effects of INK4a and ras in melanoma susceptibility in vivo
    L Chin
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Genes Dev 11:2822-34. 1997
    The 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...
  34. pmc ARF stimulates XPC to trigger nucleotide excision repair by regulating the repressor complex of E2F4
    Carmen Dominguez-Brauer
    Department of Biochemistry and Molecular Genetics, University of Illinois, College of Medicine, M C 669, 900 S Ashland Avenue, Chicago, Illinois 60607, USA
    EMBO Rep 10:1036-42. 2009
    The tumour suppressor ARF (alternative reading frame), which is mutated or silenced in various tumours, has a crucial role in tumour surveillance to suppress unwarranted cell growth and proliferation...
  35. pmc Activated TNF-alpha/NF-kappaB signaling via down-regulation of Fas-associated factor 1 in asbestos-induced mesotheliomas from Arf knockout mice
    Deborah A Altomare
    Human Genetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    Proc Natl Acad Sci U S A 106:3420-5. 2009
    The human CDKN2A locus encodes 2 distinct proteins, p16(INK4A) 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 ..
  36. ncbi LKB1 modulates lung cancer differentiation and metastasis
    Hongbin 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...
  37. ncbi Loss of one allele of ARF rescues Mdm2 haploinsufficiency effects on apoptosis and lymphoma development
    Christine M Eischen
    Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE 68198, USA
    Oncogene 23:8931-40. 2004
    The tumor suppressor p19ARF inhibits Mdm2, which restricts the activity of p53. Complicated feedback and control mechanisms regulate ARF, Mdm2, and p53 interactions...
  38. ncbi Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1
    Atsushi 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...
  39. pmc Genetic analysis of Pten and Ink4a/Arf interactions in the suppression of tumorigenesis in mice
    Mingjian 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. 2002
    Dual inactivation of PTEN and INK4a/ARF tumor suppressor genes is a common feature observed in a broad spectrum of human cancer types...
  40. pmc Rescue of key features of the p63-null epithelial phenotype by inactivation of Ink4a and Arf
    Xiaohua 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...
  41. pmc Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse
    Nabeel 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
    Activating KRAS mutations and p16(Ink4a) inactivation are near universal events in human pancreatic ductal adenocarcinoma (PDAC)...
  42. pmc Somatic integration of an oncogene-harboring Sleeping Beauty transposon models liver tumor development in the mouse
    Corey 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...
  43. pmc The inherent instability of mutant p53 is alleviated by Mdm2 or p16INK4a loss
    Tamara Terzian
    Department of Cancer Genetics, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Genes Dev 22:1337-44. 2008
    ..the regulation of mutant p53 stability by Mdm2, an E3 ubiquitin ligase that targets p53 for degradation, and p16INK4a, a member of the Rb tumor suppressor pathway...
  44. ncbi The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus
    J 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...
  45. pmc Arf-dependent regulation of Pdgf signaling in perivascular cells in the developing mouse eye
    Ricardo 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...
  46. pmc Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways
    Anna 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...
  47. pmc INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53
    C A Schmitt
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Genes Dev 13:2670-7. 1999
    The INK4a/ARF locus encodes upstream regulators of the retinoblastoma and p53 tumor suppressor gene products...
  48. ncbi Arf-induced turnover of the nucleolar nucleophosmin-associated SUMO-2/3 protease Senp3
    Mei 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. 2008
    The 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)...
  49. ncbi The PTEN and INK4A/ARF tumor suppressors maintain myelolymphoid homeostasis and cooperate to constrain histiocytic sarcoma development in humans
    Daniel R Carrasco
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Cell 9:379-90. 2006
    ..Similarly, human HS showed genetic or epigenetic inactivation of PTEN, p16(INK4A), and p14(ARF), supporting the relevance of this genetically engineered mouse model of HS...
  50. ncbi ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in mice
    Al 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...
  51. pmc Ink4a/Arf tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse
    Christine 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. 2007
    The 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...
  52. ncbi Tumor spectrum in ARF-deficient mice
    T 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. 1999
    The 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...
  53. pmc Overexpression of the cell cycle inhibitor p16INK4a promotes a prothrombotic phenotype following vascular injury in mice
    Jessica 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. 2011
    Age-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...
  54. ncbi Loss of p16Ink4a confers susceptibility to metastatic melanoma in mice
    P 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...
  55. ncbi AP-1 dimers regulate transcription of the p14/p19ARF tumor suppressor gene
    Maya 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...
  56. ncbi Cell type-specific tumor suppression by Ink4a and Arf in Kras-induced mouse gliomagenesis
    Lene Uhrbom
    Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala, Sweden
    Cancer Res 65:2065-9. 2005
    Homozygous deletion of the INK4a-ARF locus is one of the most frequent mutations found in human glioblastoma...
  57. doi PAX3-FOXO1 induces cannabinoid receptor 1 to enhance cell invasion and metastasis
    Amy 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...
  58. ncbi Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation
    Nabeel 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...
  59. pmc Sarcomas induced in discrete subsets of prospectively isolated skeletal muscle cells
    Simone Hettmer
    The Howard Hughes Medical Institute and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 108:20002-7. 2011
    ..of Kirsten rat sarcoma viral oncogene [Kras(G12V)] and disruption of cyclin-dependent kinase inhibitor 2A (CDKN2A; p16p19) in prospectively isolated satellite cells gave rise to pleomorphic rhabdomyosarcomas (MyoD-, Myogenin- ..
  60. pmc Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma
    Andrew 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...
  61. pmc Bidirectional autoregulatory mechanism of metastasis-associated protein 1-alternative reading frame pathway in oncogenesis
    Da 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
    ..unrecognized bidirectional autoregulatory loop between MTA1 and tumor suppressor alternative reading frame (ARF)...
  62. pmc A novel zinc finger protein Zfp277 mediates transcriptional repression of the Ink4a/arf locus through polycomb repressive complex 1
    Masamitsu 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...
  63. ncbi Essential role for oncogenic Ras in tumour maintenance
    L 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...
  64. pmc Mdm2 regulates p53 independently of p19(ARF) in homeostatic tissues
    Kathleen 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 ..
  65. pmc A KrasG12D-driven genetic mouse model of pancreatic cancer requires glypican-1 for efficient proliferation and angiogenesis
    C 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)...
  66. pmc Identification of candidate cancer-causing genes in mouse brain tumors by retroviral tagging
    Fredrik 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...
  67. pmc Transient expression of the Arf tumor suppressor during male germ cell and eye development in Arf-Cre reporter mice
    Adam 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. 2009
    The Arf tumor suppressor is expressed transiently during mouse male germ cell and eye development...
  68. doi Activated STAT5 promotes long-lived cytotoxic CD8+ T cells that induce regression of autochthonous melanoma
    Magali 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
    ....
  69. ncbi p16Ink4a or p19Arf loss contributes to Tal1-induced leukemogenesis in mice
    J 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)...
  70. ncbi Modeling INK4/ARF tumor suppression in the mouse
    Justin H Berger
    Massachusetts General Hospital Cancer Center, Department of Medicine, Harvard Medical School, Boston, MA 02114, USA
    Curr Mol Med 7:63-75. 2007
    The 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...
  71. pmc The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells
    Adrian P Bracken
    Centre for Epigenetics, Biotech Research and Innovation Centre BRIC, University of Copenhagen, Copenhagen 2200, Denmark
    Genes Dev 21:525-30. 2007
    The 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...
  72. pmc Inactivation of TIF1gamma cooperates with Kras to induce cystic tumors of the pancreas
    David F Vincent
    INSERM, U590, IFR62, Lyon, France
    PLoS Genet 5:e1000575. 2009
    ....
  73. pmc Ink4a/Arf expression is a biomarker of aging
    Janakiraman 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. 2004
    The Ink4a/Arf locus encodes 2 tumor suppressor molecules, p16INK4a and Arf, which are principal mediators of cellular senescence...
  74. ncbi Impaired processing of DNA photoproducts and ultraviolet hypermutability with loss of p16INK4a or p19ARF
    Papri 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...
  75. pmc Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis
    Matthieu 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...
  76. pmc Differential impact of Ink4a and Arf on hematopoietic stem cells and their bone marrow microenvironment in Bmi1-deficient mice
    Hideyuki 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...
  77. ncbi Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis
    N 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. 2001
    The 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...
  78. ncbi Expression of the p16INK4a tumor suppressor versus other INK4 family members during mouse development and aging
    F Zindy
    Department of Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Oncogene 15:203-11. 1997
    ..Both p18INK4c and p19INK4d were widely expressed during mouse embryogenesis, but p16INK4a and p15INK4b were not readily detected prenatally...
  79. doi Mitochondrial p32 is a critical mediator of ARF-induced apoptosis
    Koji Itahana
    Department of Radiation Oncology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7512, USA
    Cancer Cell 13:542-53. 2008
    The shared exon 2 of the p14ARF-p16INK4a locus is frequently mutated in human cancers. However, in contrast to the exon 1beta-encoded N-terminal half of ARF, the function of the exon 2-encoded C-terminal half of ARF has been elusive...
  80. pmc Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locus
    Alexandros 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...
  81. ncbi Mice doubly deficient for the Polycomb Group genes Mel18 and Bmi1 reveal synergy and requirement for maintenance but not initiation of Hox gene expression
    T 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...
  82. pmc Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53
    R 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...
  83. ncbi Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched
    C 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...
  84. doi Thymocyte proliferation induced by pre-T cell receptor signaling is maintained through polycomb gene product Bmi-1-mediated Cdkn2a repression
    Masaki Miyazaki
    Department of Immunology, Graduate School of Biomedical Science, Hiroshima University, 1 2 3 Kasumi, Minami Ku, Hiroshima 734 8551, Japan
    Immunity 28:231-45. 2008
    ..cells induced by pre-TCR signaling required the Polycomb group (PcG) gene product Bmi-1-mediated repression of Cdkn2A, and that p19Arf expression resulted in thymocyte cell death and inhibited the transition from CD4(-)CD8(-) (DN) ..
  85. ncbi Tumour biology: Policing of oncogene activity by p53
    Alejo Efeyan
    Spanish National Cancer Centre CNIO, Madrid 28029, Spain
    Nature 443:159. 2006
  86. ncbi Genome-wide retroviral insertional tagging of genes involved in cancer in Cdkn2a-deficient mice
    Anders 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...
  87. ncbi Polycomb complexes regulate cellular senescence by repression of ARF in cooperation with E2F3
    Jun 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...
  88. ncbi Role of genomic instability and p53 in AID-induced c-myc-Igh translocations
    Almudena 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 ..
  89. pmc E1A signaling to p53 involves the p19(ARF) tumor suppressor
    E 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)...
  90. pmc 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 mice
    K 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 ..
  91. doi ARF suppresses tumor angiogenesis through translational control of VEGFA mRNA
    Hiroyuki 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 ..
  92. ncbi Genetic determinants of malignancy in a mouse model for oligodendroglioma
    William A Weiss
    Department of Neurology, University of California, San Francisco, California 94143 0663, USA
    Cancer Res 63:1589-95. 2003
    Oligodendrogliomas of all grades overexpress epidermal growth factor receptor (EGFR), whereas deletion of ink4a/arf is found only in high-grade tumors...
  93. ncbi Cooperativity of p19ARF, Mdm2, and p53 in murine tumorigenesis
    Lynette Moore
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Oncogene 22:7831-7. 2003
    The 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...
  94. pmc Differential p53-independent outcomes of p19(Arf) loss in oncogenesis
    Zhenbang Chen
    Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Harvard Medical School, Boston, MA 02115, USA
    Sci Signal 2:ra44. 2009
    One reported function of the tumor suppressor p19(Arf) is to stabilize p53, providing a critical checkpoint in the response to oncogenic insults...
  95. pmc Nucleophosmin is required for DNA integrity and p19Arf protein stability
    Emanuela Colombo
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    Mol Cell Biol 25:8874-86. 2005
    Nucleophosmin (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...
  96. pmc mTOR promotes survival and astrocytic characteristics induced by Pten/AKT signaling in glioblastoma
    Xiaoyi Hu
    Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Neoplasia 7:356-68. 2005
    ....
  97. pmc Sumoylation induced by the Arf tumor suppressor: a p53-independent function
    Kenji 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. 2005
    The mouse p19(Arf) protein has both p53-dependent and p53-independent tumor-suppressive activities...
  98. pmc The Arf tumor suppressor gene promotes hyaloid vascular regression during mouse eye development
    Robyn 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. 2002
    A key tumor suppressor mechanism that is disrupted frequently in human cancer involves the ARF and p53 genes...
  99. ncbi Oncogenic activity of Cdc6 through repression of the INK4/ARF locus
    Susana Gonzalez
    Tumor Suppression Group, Spanish National Cancer Research Center CNIO, E 28029 Madrid, Spain
    Nature 440:702-6. 2006
    The INK4/ARF locus encodes three tumour suppressors (p15(INK4b), ARF and p16(INK4a)) and is among the most frequently inactivated loci in human cancer...
  100. ncbi Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway
    Dmitry 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...
  101. pmc Dicer inactivation in osteoprogenitor cells compromises fetal survival and bone formation, while excision in differentiated osteoblasts increases bone mass in the adult mouse
    Tripti Gaur
    Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Dev Biol 340:10-21. 2010
    ..We propose that Dicer generated miRs are essential for two periods of bone formation, to promote osteoblast differentiation before birth, and control bone accrual in the adult...

Research Grants59

  1. The role of p16INK4a in mammalian aging
    Norman Edward Sharpless; Fiscal Year: 2010
    Work, from our lab and others, has established that the beneficial, anti-cancer function of the p16INK4a tumor suppressor mechanism also untowardly contributes to mammalian aging...
  2. Mouse Model of Pancreatic Cancer Progression-Maintenance
    Nabeel Bardeesy; Fiscal Year: 2007
    Activating mutations of KRAS and losses of INK4a/ARF are thought to occur at the early stages of pancreatic adenocarcinoma pathogenesis while losses of p53 and SMAD4 are associated with the emergence of more advanced lesions...
  3. Melanoma in p16INK4a and p19ARF Deficient Mice
    NORMAN 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 ..
  4. The role of p16INK4a in mammalian aging
    NORMAN SHARPLESS; Fiscal Year: 2007
    ..As the only known function of p16INK4a is to induce cell cycle arrest, this increased p16 INK4a expression may play a significant role in the impaired tissue regeneration and stem cell function characteristic ..
  5. A flexible somatic and sporadic mouse model for pancreatic ductal adenocarcinoma
    Brian Lewis; Fiscal Year: 2007
    ..Such an advance would benefit public health by reducing the mortality associated with this disease. ..
  6. Molecular dissection of pancreatic ductal adenocarcinoma
    Brian Lewis; Fiscal Year: 2009
    ..Such gene expression signatures may potentially be used as diagnostic tools, as well as surrogate markers for response to targeted therapeutic interventions. ..
  7. Molecular dissection of pancreatic ductal adenocarcinoma
    Brian C Lewis; Fiscal Year: 2010
    ..Such gene expression signatures may potentially be used as diagnostic tools, as well as surrogate markers for response to targeted therapeutic interventions. ..
  8. Molecular mediators of metastasis in hepatocellular carcinoma
    Brian 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...
  9. Molecular dissection of pancreatic ductal adenocarcinoma
    Brian Lewis; Fiscal Year: 2009
    ..Such gene expression signatures may potentially be used as diagnostic tools, as well as surrogate markers for response to targeted therapeutic interventions. ..
  10. Molecular mediators of metastasis in hepatocellular carcinoma
    Brian Lewis; Fiscal Year: 2009
    ..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...
  11. Molecular dissection of pancreatic ductal adenocarcinoma
    Brian C Lewis; Fiscal Year: 2010
    ..Such gene expression signatures may potentially be used as diagnostic tools, as well as surrogate markers for response to targeted therapeutic interventions. ..
  12. Molecular mediators of metastasis in hepatocellular carcinoma
    Brian Lewis; Fiscal Year: 2007
    ..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...
  13. p53-Independent Pathways in Mdm2-Mediated Transformation
    Christine M Eischen; Fiscal Year: 2010
    ..Results from these studies should ultimately lead to improved therapeutic strategies for the treatment of lymphomas and other human malignancies in which Mdm2 is overexpressed. ..
  14. p53-Independent Pathways in Mdm2-Mediated Transformation
    CHRISTINE EISCHEN; Fiscal Year: 2007
    ..Results from these studies should ultimately lead to improved therapeutic strategies for the treatment of lymphomas and other human malignancies in which Mdm2 is overexpressed. ..
  15. The Role of Mdm2 in Lymphoma Development
    CHRISTINE EISCHEN; Fiscal Year: 2007
    ..Surprisingly, Mdm2 overexpression frequently occurred in lymphomas that had inactivated p53 or p19ARF, a regulator of Mdm2...
  16. The genetic Basis of Melanoma Metastasis
    Lynda Chin; Fiscal Year: 2007
    ....
  17. TOR, Translation and Aging
    Brian Kennedy; Fiscal Year: 2009
    ..Through achieving a better understand of the modulatory role played by regulated protein translation in aging, we will be able to pinpoint key targets for pharmacological interventions. ..
  18. Genome-wide Analysis of Aging in Yeast
    Brian Kennedy; Fiscal Year: 2009
    ..When completed, this study will dramatically improve our understanding of aging in yeast and lead to models of caloric restriction that can be tested in mammalian systems. ..
  19. Nuclear Lamin Functions and Human Disease
    Brian Kennedy; Fiscal Year: 2009
    ..Findings from these studies will identify and test potential mechanistic underpinnings that underlie Hutchinson-Gilford progeria syndrome and other A-type lamin-associated diseases. ..
  20. S6 Kinase, Aging and Age-related Disease
    Brian Kennedy; Fiscal Year: 2009
    ..We have determined that reduced S6 kinase function leads to lifespan extension in organisms ranging from yeast to mice. In this proposal, we will dissect the mechanisms by which S6 kinase activity accelerates the aging process. ..
  21. MOLECULAR PATHOGENESIS OF MALIGNANT MELANOMA
    Lynda 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...
  22. Genomic & Genetic Characterization of Amplicons in GBMs
    Lynda Chin; Fiscal Year: 2007
    ..The highest potential candidate glioma oncogene will be further validated by rigorous in vivo transgenesis study. ..
  23. Nuclear Lamin Functions and Human Disease
    Brian Kennedy; Fiscal Year: 2007
    ..Myoblast cell lines, generated from Lmna-/- mice, exhibit differentiation defects. These defects will be studied at the molecular level to better understand how aberrant A-type lamin function leads to tissue degeneration. ..
  24. MET Activation in Melanoma Genesis and Progression
    Lynda Chin; Fiscal Year: 2006
    ..will be examined on phenotypic, molecular/genetic and genomic levels to validate a role for MET in progression, and ultimately to delineate genes and pathways critically important for tumor progression, and possibly metastasis ..
  25. Genome-wide Analysis of Aging in Yeast
    Brian Kennedy; Fiscal Year: 2007
    ..When completed, this study will dramatically improve our understanding of aging in yeast and lead to models of caloric restriction that can be tested in mammalian systems. ..
  26. The genetic Basis of Melanoma Metastasis
    Lynda Chin; Fiscal Year: 2010
    ..pursue the validation of new metastasis candidates through low-complexity in vivo genetic screens followed by rigorous functional and clinical validation in human melanoma cells and melanoma specimen on TMA, respectively ..