The INK4a/ARF tumor suppressor: one gene - two products - two pathways

被引：235
作者：
Chin, L
Pomerantz, J
DePinho, RA
机构：
[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA
[3] Albert Einstein Coll Med, Dept Microbiol & Immunol, New York, NY 10461 USA
[4] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
来源：
TRENDS IN BIOCHEMICAL SCIENCES | 1998年 / 23卷 / 08期
关键词：
D O I：
10.1016/S0968-0004(98)01236-5
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：
Functional inactivation of the retinoblastoma (RB) and p53 pathways appears to be a rite of passage for all cancerous cells and results in disruption of cell-cycle regulation and deactivation of the apoptotic response that normally ensues. The INK4a/ARF locus sits at the nexus of these two growth-control pathways, by virtue of its ability to generate two distinct products: the p16(INK4a) protein, a cyclin-dependent kinase inhibitor that functions upstream of RE; and the p19(ARF) protein, which blocks MDM2 inhibition of p53 activity. This 'one gene - two products - two pathways' arrangement provides a basis for the prominence of INK4a/ARF in tumorigenesis.
引用
收藏
页码：291 / 296
页数：6
相关论文
共 50 条
[1]   ASSIGNMENT OF A LOCUS FOR FAMILIAL MELANOMA, MLM, TO CHROMOSOME-9P13-P22 [J].
CANNONALBRIGHT, LA ;
GOLDGAR, DE ;
MEYER, LJ ;
LEWIS, CM ;
ANDERSON, DE ;
FOUNTAIN, JW ;
HEGI, ME ;
WISEMAN, RW ;
PETTY, EM ;
BALE, AE ;
OLOPADE, OI ;
DIAZ, MO ;
KWIATKOWSKI, DJ ;
PIEPKORN, MW ;
ZONE, JJ ;
SKOLNICK, MH .
SCIENCE, 1992, 258 (5085) :1148-1152
[2]   Cooperative effects of INK4a and ras in melanoma susceptibility in vivo [J].
Chin, L ;
Pomerantz, J ;
Polsky, D ;
Jacobson, M ;
Cohen, C ;
CordonCardo, C ;
Horner, JW ;
DePinho, RA .
GENES & DEVELOPMENT, 1997, 11 (21) :2822-2834
[3]   Transcriptional repression - The cancer-chromatin connection [J].
DePinho, RA .
NATURE, 1998, 391 (6667) :533-+
[4]  
DURO D, 1995, ONCOGENE, V11, P21
[5]   Genomic alterations of the p19ARF encoding exons in T-cell acute lymphoblastic leukemia [J].
Gardie, B ;
Cayuela, JM ;
Martini, S ;
Sigaux, F .
BLOOD, 1998, 91 (03) :1016-1020
[6]  
GLENDENING JM, 1995, CANCER RES, V55, P5531
[7]   Database of p53 gene somatic mutations in human tumors and cell lines: Updated compilation and future prospects [J].
Hainaut, P ;
Soussi, T ;
Shomer, B ;
Hollstein, M ;
Greenblatt, M ;
Hovig, E ;
Harris, CC ;
Montesano, R .
NUCLEIC ACIDS RESEARCH, 1997, 25 (01) :151-157
[8]  
Hall M, 1996, ADV CANCER RES, V68, P67, DOI 10.1016/S0065-230X(08)60352-8
[9]  
Harper JW, 1996, CURR OPIN GENET DEV, V6, P56
[10]   Mdm2 promotes the rapid degradation of p53 [J].
Haupt, Y ;
Maya, R ;
Kazaz, A ;
Oren, M .
NATURE, 1997, 387 (6630) :296-299
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