BCL-2 HETERODIMERIZES IN-VIVO WITH A CONSERVED HOMOLOG, BAX, THAT ACCELERATES PROGRAMMED CELL-DEATH

被引：5528

作者：

OLTVAI, ZN ^{[1
]}

MILLIMAN, CL ^{[1
]}

KORSMEYER, SJ ^{[1
]}

机构：

[1] WASHINGTON UNIV, SCH MED, HOWARD HUGHES MED INST, DEPT PATHOL, ST LOUIS, MO 63110 USA

来源：

CELL | 1993年 / 74卷 / 04期

关键词：

D O I：

10.1016/0092-8674(93)90509-O

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：

Bcl-2 protein is able to repress a number of apoptotic death programs. To investigate the mechanism of Bcl-2's effect, we examined whether Bcl-2 interacted with other proteins. We identified an associated 21 kd protein partner, Bax, that has extensive amino acid homology with Bcl-2, focused within highly conserved domains I and II. Bax is encoded by six exons and demonstrates a complex pattern of alternative RNA splicing that predicts a 21 kd membrane (alpha) and two forms of cytosolic protein (beta and gamma). Bax homodimerizes and forms heterodimers with Bcl-2 in vivo. Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line. Overexpressed Bax also counters the death repressor activity of Bcl-2. These data suggest a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus.

引用

页码：609 / 619

页数：11

共 61 条

[1] THE PROTOONCOGENE BCL-2 CAN SELECTIVELY RESCUE NEUROTROPHIC FACTOR-DEPENDENT NEURONS FROM APOPTOSIS [J].

ALLSOPP, TE ;

WYATT, S ;

PATERSON, HF ;

DAVIES, AM .

CELL, 1993, 73 (02) :295-307

[2] BASIC LOCAL ALIGNMENT SEARCH TOOL [J].

ALTSCHUL, SF ;

GISH, W ;

MILLER, W ;

MYERS, EW ;

LIPMAN, DJ .

JOURNAL OF MOLECULAR BIOLOGY, 1990, 215 (03) :403-410

[3] ONCOGENIC ACTIVITY OF THE C-MYC PROTEIN REQUIRES DIMERIZATION WITH MAX [J].

AMATI, B ;

BROOKS, MW ;

LEVY, N ;

LITTLEWOOD, TD ;

EVAN, GI ;

LAND, H .

CELL, 1993, 72 (02) :233-245

[4] IDENTIFICATION OF A CDNA FOR A HUMAN HIGH-MOLECULAR-WEIGHT B-CELL GROWTH-FACTOR [J].

AMBRUS, JL ;

PIPPIN, J ;

JOSEPH, A ;

XU, CG ;

BLUMENTHAL, D ;

TAMAYO, A ;

CLAYPOOL, K ;

MCCOURT, D ;

SRIKIATCHATOCHORN, A ;

FORD, RJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (13) :6330-6334

[5] MAD - A HETERODIMERIC PARTNER FOR MAX THAT ANTAGONIZES MYC TRANSCRIPTIONAL ACTIVITY [J].

AYER, DE ;

KRETZNER, L ;

EISENMAN, RN .

CELL, 1993, 72 (02) :211-222

[6] A CHIMERIC MAMMALIAN TRANSACTIVATOR BASED ON THE LAC REPRESSOR THAT IS REGULATED BY TEMPERATURE AND ISOPROPYL BETA-D-THIOGALACTOPYRANOSIDE [J].

BAIM, SB ;

LABOW, MA ;

LEVINE, AJ ;

SHENK, T .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (12) :5072-5076

[7] CLONING THE CHROMOSOMAL BREAKPOINT OF T(14-18) HUMAN LYMPHOMAS - CLUSTERING AROUND JH ON CHROMOSOME-14 AND NEAR A TRANSCRIPTIONAL UNIT ON 18 [J].

BAKHSHI, A ;

JENSEN, JP ;

GOLDMAN, P ;

WRIGHT, JJ ;

MCBRIDE, OW ;

EPSTEIN, AL ;

KORSMEYER, SJ .

CELL, 1985, 41 (03) :899-906

[8] CELL-DEATH AND CONTROL OF CELL-SURVIVAL IN THE OLIGODENDROCYTE LINEAGE [J].

BARRES, BA ;

HART, IK ;

COLES, HSR ;

BURNE, JF ;

VOYYODIC, JT ;

RICHARDSON, WD ;

RAFF, MC .

CELL, 1992, 70 (01) :31-46

[9]

BATISTATOU A, 1993, IN PRESS J NEUROSCI

[10] ALTERNATIVE 5' EXONS IN C-ABL MESSENGER-RNA [J].

BEN-NERIAH, Y ;

BERNARDS, A ;

PASKIND, M ;

DALEY, GQ ;

BALTIMORE, D .

CELL, 1986, 44 (04) :577-586

← 1 2 3 4 5 6 7 →