The INK4A/ARF locus:: Role in cell cycle control and apoptosis and implications for glioma growth

被引:58
作者
Ivanchuk, SM
Mondal, S
Dirks, PB
Rutka, JT
机构
[1] Univ Toronto, Hosp Sick Children, Div Neurosurg, Toronto, ON M5G 1X8, Canada
[2] Univ Toronto, Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1X8, Canada
关键词
apoptosis; growth arrest; INK4A/ARF; p53; pRB; tumour suppressor;
D O I
10.1023/A:1010632309113
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The unique INK4A/ARF locus at chromosome 9p21 encodes two distinct proteins that intimately link the pRB and p53 tumour suppressor pathways. p16(INK4A) has been identified as an inhibitor of the cell cycle, capable of inducing arrest in G1 phase. p14/p19(ARF) on the other hand can induce both G1 and G2 arrest due to its stabilizing effects on the p53 transcription factor. In addition to their roles in growth arrest, both proteins are involved in cellular senescence and apoptosis. The frequent mutation or deletion of INK4A/ARF in human tumours as well as the occurence of tumours in the murine knockout models have identified both p16 and ARF as bona fide tumour suppressors.
引用
收藏
页码:219 / 229
页数:11
相关论文
共 70 条
[1]   Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts [J].
Alcorta, DA ;
Xiong, Y ;
Phelps, D ;
Hannon, G ;
Beach, D ;
Barrett, JC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (24) :13742-13747
[2]   Functional analysis of wild-type and malignant glioma derived CDKN2A beta alleles: Evidence for an RB-independent growth suppressive pathway [J].
Arap, W ;
Knudsen, E ;
Sewell, DA ;
Sidransky, D ;
Wang, JYJ ;
Huang, HJS ;
Cavenee, WK .
ONCOGENE, 1997, 15 (17) :2013-2020
[3]   Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d [J].
Brotherton, DH ;
Dhanaraj, V ;
Wick, S ;
Brizuela, L ;
Domaille, PJ ;
Volyanik, E ;
Xu, X ;
Parisini, E ;
Smith, BO ;
Archer, SJ ;
Serrano, M ;
Brenner, SL ;
Blundell, TL ;
Laue, ED .
NATURE, 1998, 395 (6699) :244-250
[4]   Tumor suppressor p16INK4A:: Determination of solution structure and analyses of its interaction with cyclin-dependent kinase 4 [J].
Byeon, IJL ;
Li, JN ;
Ericson, K ;
Selby, TL ;
Tevelev, A ;
Kim, HJ ;
O'Maille, P ;
Tsai, MD .
MOLECULAR CELL, 1998, 1 (03) :421-431
[5]  
CAMERO A, 2000, NAT CELL BIOL, V2, P148
[6]  
Campagne MV, 1998, J COMP NEUROL, V397, P181
[7]   Adenovirus-mediated p16/CDKN2 gene transfer suppresses glioma invasion in vitro [J].
Chintala, SK ;
Fueyo, J ;
GomezManzano, C ;
Venkaiah, B ;
Bjerkvig, R ;
Yung, WKA ;
Sawaya, R ;
Kyritsis, AP ;
Rao, JS .
ONCOGENE, 1997, 15 (17) :2049-2057
[8]   Restoration of growth arrest by p16INK4, p21WAF1, pRB, and p53 is dependent on the integrity of the endogenous cell-cycle control pathways in human glioblastoma cell lines [J].
Costanzi-Strauss, E ;
Strauss, BE ;
Naviaux, RK ;
Haas, M .
EXPERIMENTAL CELL RESEARCH, 1998, 238 (01) :51-62
[9]   E1A signaling to p53 involves the p19ARF tumor suppressor [J].
de Stanchina, E ;
McCurrach, ME ;
Zindy, F ;
Shieh, SY ;
Ferbeyre, G ;
Samuelson, AV ;
Prives, C ;
Roussel, MF ;
Sherr, CJ ;
Lowe, SW .
GENES & DEVELOPMENT, 1998, 12 (15) :2434-2442
[10]   Retinoic acid and the cyclin dependent kinase inhibitors synergistically alter proliferation and morphology of U343 astrocytoma cells [J].
Dirks, PB ;
Patel, K ;
Hubbard, SL ;
Ackerley, C ;
Hamel, PA ;
Rutka, JT .
ONCOGENE, 1997, 15 (17) :2037-2048