The regulation of INK4/ARF in cancer and aging

被引:820
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 [J].
Allsopp, RC ;
Morin, GB ;
Horner, JW ;
DePinho, R ;
Harley, CB ;
Weissman, IL .
NATURE MEDICINE, 2003, 9 (04) :369-U6
[2]   Repression of the Arf tumor suppressor by E2F3 is required for normal cell cycle kinetics [J].
Aslanian, A ;
Iaquinta, PJ ;
Verona, R ;
Lees, JA .
GENES & DEVELOPMENT, 2004, 18 (12) :1413-1422
[3]   Both p16Ink4a and the p19Arf-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse [J].
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 .
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 [J].
Bates, S ;
Phillips, AC ;
Clark, PA ;
Stott, F ;
Peters, G ;
Ludwig, RL ;
Vousden, KH .
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 [J].
Ben-Saadon, R ;
Fajerman, I ;
Ziv, T ;
Hellman, U ;
Schwartz, AL ;
Ciechanover, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (40) :41414-41421
[6]   Oncogene-induced senescence as an initial barrier in lymphoma development [J].
Braig, M ;
Lee, S ;
Loddenkemper, C ;
Rudolph, C ;
Peters, AHFM ;
Schlegelberger, B ;
Stein, H ;
Dörken, B ;
Jenuwein, T ;
Schmitt, CA .
NATURE, 2005, 436 (7051) :660-665
[7]   Ink4a and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1-deficient mice [J].
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 .
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 [J].
Bulavin, DV ;
Phillips, C ;
Nannenga, B ;
Timofeev, O ;
Donehower, LA ;
Anderson, CW ;
Appella, E ;
Fornace, AJ .
NATURE GENETICS, 2004, 36 (04) :343-350
[9]   Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer [J].
Burri, N ;
Shaw, P ;
Bouzourene, H ;
Sordat, I ;
Sordat, B ;
Gillet, M ;
Schorderet, D ;
Bosman, FT ;
Chaubert, P .
LABORATORY INVESTIGATION, 2001, 81 (02) :217-229
[10]   Senescent cells, tumor suppression, and organismal aging: Good citizens, bad neighbors [J].
Campisi, J .
CELL, 2005, 120 (04) :513-522