The proto-oncogene c-myc and apoptosis

被引:134
作者
Hoffman, B
Liebermann, DA
机构
[1] Temple Univ, Fels Inst Canc Res & Mol Biol, Sch Med, Philadelphia, PA 19140 USA
[2] Temple Univ, Dept Biochem, Sch Med, Philadelphia, PA 19140 USA
关键词
c-myc; proliferation; apoptosis; tumorigenesis;
D O I
10.1038/sj.onc.1202592
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
Deregulated expression of c-Myc not only promotes proliferation, but also can either induce or sensitize cells to apoptosis, Inappropriate expression of c-Myc under conditions which inhibit growth and down-regulate endogenous c-Myc expression, including serum deprivation and exposure to cytotoxic agents including the anticancer agents vinblastine, etoposide, Ara-C, and nocodazole, usually results in programmed cell death in many different cell types. Also, inappropriate Myc expression is associated with an apoptotic response elicited by induction of differentiation. The proapoptotic property of c-Myc requires an intact N-terminal transactivation domain and bHLHZip domain, as well as interaction with Max, thereby implicating c-Myc target genes in this apoptotic process. Although some target genes, namely cdc25A and ODC, have been shown to participate in Myc-mediated apoptosis, no target gene has yet been identified which is essential for this apoptotic response. It is possible that the response of cells inappropriately expressing c-Myc is due not only to the growth arrest signals per se, but also to signals elicited by specific growth inhibitors in the context of a particular biological setting. Also regulating the response of the cells is expression of other oncogenes and tumor suppressor genes, as well as paracrine and autocrine survival factors. Apoptosis associated with inappropriate Myc expression limits the tumorigenic effect of the c-myc proto-oncogene, Mechanisms which inhibit apoptosis should enhance or promote tumorigenesis.
引用
收藏
页码:3351 / 3357
页数:7
相关论文
共 92 条
[1]   The Bcl-2 protein family: Arbiters of cell survival [J].
Adams, JM ;
Cory, S .
SCIENCE, 1998, 281 (5381) :1322-1326
[2]   Role for N-CoR and histone deacetylase in Sin3-mediated transcriptional repression [J].
Alland, L ;
Muhle, R ;
Hou, H ;
Potes, J ;
Chin, L ;
SchreiberAgus, N ;
DePinho, RA .
NATURE, 1997, 387 (6628) :49-55
[3]  
ALNEMRI ES, 1992, CANCER RES, V52, P491
[4]   MYC-MAX-MAD - A TRANSCRIPTION FACTOR NETWORK CONTROLLING CELL-CYCLE PROGRESSION, DIFFERENTIATION AND DEATH [J].
AMATI, B ;
LAND, H .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 1994, 4 (01) :102-108
[5]   THE C-MYC PROTEIN INDUCES CELL-CYCLE PROGRESSION AND APOPTOSIS THROUGH DIMERIZATION WITH MAX [J].
AMATI, B ;
LITTLEWOOD, TD ;
EVAN, GI ;
LAND, H .
EMBO JOURNAL, 1993, 12 (13) :5083-5087
[6]  
ASKEW DS, 1991, ONCOGENE, V6, P1915
[7]  
ASKEW DS, 1993, BLOOD, V82, P2079
[8]   ORNITHINE DECARBOXYLASE ACTIVITY IS CRITICAL FOR CELL-TRANSFORMATION [J].
AUVINEN, M ;
PAASINEN, A ;
ANDERSSON, LC ;
HOLTTA, E .
NATURE, 1992, 360 (6402) :355-358
[9]   MAD-MAX TRANSCRIPTIONAL REPRESSION IS MEDIATED BY TERNARY COMPLEX-FORMATION WITH MAMMALIAN HOMOLOGS OF YEAST REPRESSOR SIN3 [J].
AYER, DE ;
LAWRENCE, QA ;
EISENMAN, RN .
CELL, 1995, 80 (05) :767-776
[10]   MAD - A HETERODIMERIC PARTNER FOR MAX THAT ANTAGONIZES MYC TRANSCRIPTIONAL ACTIVITY [J].
AYER, DE ;
KRETZNER, L ;
EISENMAN, RN .
CELL, 1993, 72 (02) :211-222