The regulation of INK4/ARF in cancer and aging

被引:809
作者
Kim, William Y.
Sharpless, Norman E. [1 ]
机构
[1] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC 27599 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/j.cell.2006.10.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Loss of the INK4a/ARF/INK4b locus on chromosome 9p21 is among the most frequent cytogenetic events in human cancer. The products of the locus-p15(INK4b), p(16INK4a), and ARF-play widespread and independent roles in tumor suppression. Recent data also suggest that expression of p(16INK4a) induces an age-dependent decrease in the proliferative capacity of certain tissue-specific stem cells and unipotent progenitors. Here, we discuss the regulation and role of p(16INK4a), ARF, and p(15INK4b) in cancer and aging.
引用
收藏
页码:265 / 275
页数:11
相关论文
共 83 条
  • [1] Effect of TERT over-expression on the long-term transplantation capacity of hematopoietic stem cells
    Allsopp, RC
    Morin, GB
    Horner, JW
    DePinho, R
    Harley, CB
    Weissman, IL
    [J]. NATURE MEDICINE, 2003, 9 (04) : 369 - U6
  • [2] Repression of the Arf tumor suppressor by E2F3 is required for normal cell cycle kinetics
    Aslanian, A
    Iaquinta, PJ
    Verona, R
    Lees, JA
    [J]. GENES & DEVELOPMENT, 2004, 18 (12) : 1413 - 1422
  • [3] Both p16Ink4a and the p19Arf-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse
    Bardeesy, N
    Aguirre, AJ
    Chu, GC
    Cheng, KH
    Lopez, LV
    Hezel, AF
    Feng, B
    Brennan, C
    Weissleder, R
    Mahmood, U
    Hanahan, D
    Redston, MS
    Chin, L
    DePinho, RA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (15) : 5947 - 5952
  • [4] p14ARF links the tumour suppressors RB and p53
    Bates, S
    Phillips, AC
    Clark, PA
    Stott, F
    Peters, G
    Ludwig, RL
    Vousden, KH
    [J]. NATURE, 1998, 395 (6698) : 124 - 125
  • [5] The tumor suppressor protein p16INK4a and the human papillomavirus oncoprotein-58 E7 are naturally occurring lysine-less proteins that are degraded by the ubiquitin system -: Direct evidence for ubiquitination at the N-terminal residue
    Ben-Saadon, R
    Fajerman, I
    Ziv, T
    Hellman, U
    Schwartz, AL
    Ciechanover, A
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (40) : 41414 - 41421
  • [6] Oncogene-induced senescence as an initial barrier in lymphoma development
    Braig, M
    Lee, S
    Loddenkemper, C
    Rudolph, C
    Peters, AHFM
    Schlegelberger, B
    Stein, H
    Dörken, B
    Jenuwein, T
    Schmitt, CA
    [J]. NATURE, 2005, 436 (7051) : 660 - 665
  • [7] Ink4a and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1-deficient mice
    Bruggeman, SWM
    Valk-Lingbeek, ME
    van der Stoop, PPM
    Jacobs, JJL
    Kieboom, K
    Tanger, E
    Hulsman, D
    Leung, C
    Arsenijevic, Y
    Marino, S
    van Lohuizen, M
    [J]. GENES & DEVELOPMENT, 2005, 19 (12) : 1438 - 1443
  • [8] Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16Ink4a-p19Arf pathway
    Bulavin, DV
    Phillips, C
    Nannenga, B
    Timofeev, O
    Donehower, LA
    Anderson, CW
    Appella, E
    Fornace, AJ
    [J]. NATURE GENETICS, 2004, 36 (04) : 343 - 350
  • [9] Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer
    Burri, N
    Shaw, P
    Bouzourene, H
    Sordat, I
    Sordat, B
    Gillet, M
    Schorderet, D
    Bosman, FT
    Chaubert, P
    [J]. LABORATORY INVESTIGATION, 2001, 81 (02) : 217 - 229
  • [10] Senescent cells, tumor suppression, and organismal aging: Good citizens, bad neighbors
    Campisi, J
    [J]. CELL, 2005, 120 (04) : 513 - 522