p53 mutants have selective dominant-negative effects on apoptosis but not growth arrest in human cancer cell lines

被引:63
作者
Aurelio, ON [1 ]
Kong, XT [1 ]
Gupta, S [1 ]
Stanbridge, EJ [1 ]
机构
[1] Univ Calif Irvine, Coll Med, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA
关键词
D O I
10.1128/MCB.20.3.770-778.2000
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
A bidirectional expression vector that allowed equal transcription of cloned wild-type and mutant p53 cDNAs from the same vector was developed. The vector was transfected into CaLu 6 lung carcinoma cells or Saos-2 osteosarcoma cells. All p53 mutants examined were recessive to wild-type p53 transactivatioa of p21(WAF1/CIP1) but dominant-negative for transactivation of Bax. An examination of effects on growth arrest and apoptotic pathways indicated that all mutants were recessive to wild type for growth arrest but only three of seven mutants were dominant negative for induction of apoptosis.
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收藏
页码:770 / 778
页数:9
相关论文
共 50 条
[1]   Transcriptional activation by p53, but not induction of the p21 gene, is essential for oncogene-mediated apoptosis [J].
Attardi, LD ;
Lowe, SW ;
Brugarolas, J ;
Jacks, T .
EMBO JOURNAL, 1996, 15 (14) :3693-3701
[2]  
Aurelio ON, 1998, CANCER RES, V58, P2190
[3]  
BADER SA, 1991, CELL GROWTH DIFFER, V2, P245
[4]   COREGULATION OF 2 GENE ACTIVITIES BY TETRACYCLINE VIA A BIDIRECTIONAL PROMOTER [J].
BARON, U ;
FREUNDLIEB, S ;
GOSSEN, M ;
BUJARD, H .
NUCLEIC ACIDS RESEARCH, 1995, 23 (17) :3605-3606
[5]  
BOUKAMP P, 1995, ONCOGENE, V11, P961
[6]   A VARIATION IN THE STRUCTURE OF THE PROTEIN-CODING REGION OF THE HUMAN-P53 GENE [J].
BUCHMAN, VL ;
CHUMAKOV, PM ;
NINKINA, NN ;
SAMARINA, OP ;
GEORGIEV, GP .
GENE, 1988, 70 (02) :245-252
[7]   INDUCTION OF THE GROWTH INHIBITOR IGF-BINDING PROTEIN-3 BY P53 [J].
BUCKBINDER, L ;
TALBOTT, R ;
VELASCOMIGUEL, S ;
TAKENAKA, I ;
FAHA, B ;
SEIZINGER, BR ;
KLEY, N .
NATURE, 1995, 377 (6550) :646-649
[8]  
CAAMANO J, 1991, AM J PATHOL, V139, P839
[9]   GENETIC MECHANISMS OF TUMOR SUPPRESSION BY THE HUMAN P53 GENE [J].
CHEN, PL ;
CHEN, YM ;
BOOKSTEIN, R ;
LEE, WH .
SCIENCE, 1990, 250 (4987) :1576-1580
[10]   p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells [J].
Chen, XB ;
Ko, LJ ;
Jayaraman, L ;
Prives, C .
GENES & DEVELOPMENT, 1996, 10 (19) :2438-2451