Regulation of the INK4b-ARF-INK4a tumour suppressor locus:: all for one or one for all

被引:671
作者
Gil, Jesus
Peters, Gordon
机构
[1] Canc Res UK, London Res Inst, Oncol Mol Lab, London WC2A 3PX, England
[2] Univ London Imperial Coll Sci Technol & Med, Fac Med, MRC, Ctr Clin Sci, London W12 0NN, England
基金
英国医学研究理事会;
关键词
D O I
10.1038/nrm1987
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The INK4b-ARF-INK4a locus encodes two members of the INK4 family of cyclindependent kinase inhibitors, p15(INK4b) and p16(INK4a), and a completely unrelated protein, known as ARF. All three products participate in major tumour suppressor networks that are disabled in human cancer and influence key physiological processes such as replicative senescence, apoptosis and stem-cell self-renewal. Transcription from the locus is therefore kept under strict control. Mounting evidence suggests that although the individual genes can respond independently to positive and negative signals in different contexts, the entire locus might be coordinately suppressed by a cis-acting regulatory domain or by the action of Polycomb group repressor complexes.
引用
收藏
页码:667 / 677
页数:11
相关论文
共 150 条
[61]   A CELL-CYCLE REGULATOR POTENTIALLY INVOLVED IN GENESIS OF MANY TUMOR TYPES [J].
KAMB, A ;
GRUIS, NA ;
WEAVERFELDHAUS, J ;
LIU, QY ;
HARSHMAN, K ;
TAVTIGIAN, SV ;
STOCKERT, E ;
DAY, RS ;
JOHNSON, BE ;
SKOLNICK, MH .
SCIENCE, 1994, 264 (5157) :436-440
[62]  
Kamijo T, 1999, CANCER RES, V59, P2464
[63]   Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2 [J].
Kamijo, T ;
Weber, JD ;
Zambetti, G ;
Zindy, F ;
Roussel, MF ;
Sherr, CJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (14) :8292-8297
[64]   Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19(ARF) [J].
Kamijo, T ;
Zindy, F ;
Roussel, MF ;
Quelle, DE ;
Downing, JR ;
Ashmun, RA ;
Grosveld, G ;
Sherr, CJ .
CELL, 1997, 91 (05) :649-659
[65]   Comparative structure and characterization of a CDKN2 gene in a Xiphophorus fish melanoma model [J].
Kazianis, S ;
Morizot, DC ;
Della Coletta, L ;
Johnston, DA ;
Woolcock, B ;
Vielkind, JR ;
Nairn, RS .
ONCOGENE, 1999, 18 (36) :5088-5099
[66]   Computer-assisted identification of cell cycle-related genes: new targets for E2F transcription factors [J].
Kel, AE ;
Kel-Margoulis, OV ;
Farnham, PJ ;
Bartley, SM ;
Wingender, E ;
Zhang, MQ .
JOURNAL OF MOLECULAR BIOLOGY, 2001, 309 (01) :99-120
[67]   Absence of p16INK4a and truncation of ARF tumor suppressors in chickens [J].
Kim, SH ;
Mitchell, M ;
Fujii, H ;
Llanos, S ;
Peters, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (01) :211-216
[68]   Upregulation of chicken p15INK4b at senescence and in the developing brain [J].
Kim, Soo-Hyun ;
Rowe, Janice ;
Fujii, Hideta ;
Jones, Rebecca ;
Schmierer, Bernhard ;
Kong, Byung-Whi ;
Kuchler, Karl ;
Foster, Douglas ;
Ish-Horowicz, David ;
Peters, Gordon .
JOURNAL OF CELL SCIENCE, 2006, 119 (12) :2435-2443
[69]   Distinct E2F-mediated transcriptional program regulates p14ARF gene expression [J].
Komori, H ;
Enomoto, M ;
Nakamura, M ;
Iwanaga, R ;
Ohtani, K .
EMBO JOURNAL, 2005, 24 (21) :3724-3736
[70]   Transcriptional coactivator Cited2 induces Bmi1 and Mel18 and controls fibroblast proliferation via Ink4a/ARF [J].
Kranc, KR ;
Bamforth, SD ;
Bragança, J ;
Norbury, C ;
van Lohuizen, M ;
Bhattacharya, S .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (21) :7658-7666