BID: A novel BH3 domain-only death agonist

被引:798
作者
Wang, K [1 ]
Yin, XM [1 ]
Chao, DT [1 ]
Milliman, CL [1 ]
Korsmeyer, SJ [1 ]
机构
[1] WASHINGTON UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT MED & PATHOL,DIV MOL ONCOL,ST LOUIS,MO 63110
关键词
apoptosis; BCL-2; family; BID; BH3; domain; cysteine protease;
D O I
10.1101/gad.10.22.2859
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The BCL-2 family of proteins consists of both antagonists (e.g., BCL-2) and agonists (e.g., BAX) that regulate apoptosis and compete through dimerization. The BH1 and BH2 domains of BCL-2 are required to heterodimerize with BAX and to repress cell death; conversely, the BH3 domain of BAX is required to heterodimerize with BCL-2 and to promote cell death. To extend this pathway, we used interactive cloning to identify Bid, which encodes a novel death agonist that heterodimerizes with either agonists (BAX) or antagonists (BCL-2). BID possesses only the BH3 domain, lacks a carboxy-terminal signal-anchor segment, and is found in both cytosolic and membrane locations. BID counters the protective effect of BCL-2. Moreover, expression of BID, without another death stimulus, induces ICE-like proteases and apoptosis. Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. A BH3 mutant of BID that still heterodimerized with BCL-2 failed to promote apoptosis, dissociating these activities. In contrast, the only BID BH3 mutant that retained death promoting activity interacted with BAX, but not BCL-2. This BH3-only molecule supports BH3 as a death domain and favors a model in which BID represents a death ligand for the membrane-bound receptor BAX.
引用
收藏
页码:2859 / 2869
页数:11
相关论文
共 39 条
[1]   Fas-induced activation of the cell death-related protease CPP32 is inhibited by Bcl-2 and by ICE family protease inhibitors [J].
Armstrong, RC ;
Aja, T ;
Xiang, JL ;
Gaur, S ;
Krebs, JF ;
Hoang, K ;
Bai, X ;
Korsmeyer, J ;
Karanewsky, DS ;
Fritz, LC ;
Tomaselli, KJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (28) :16850-16855
[2]   INTERACTION CLONING - IDENTIFICATION OF A HELIX-LOOP-HELIX ZIPPER PROTEIN THAT INTERACTS WITH C-FOS [J].
BLANAR, MA ;
RUTTER, WJ .
SCIENCE, 1992, 256 (5059) :1014-1018
[3]  
Boulakia CA, 1996, ONCOGENE, V12, P529
[4]  
BOYD JM, 1995, ONCOGENE, V11, P1921
[5]   Bax-independent inhibition of apoptosis by Bcl-x(L) [J].
Cheng, EHY ;
Levine, B ;
Boise, LH ;
Thompson, CB ;
Hardwick, JM .
NATURE, 1996, 379 (6565) :554-556
[6]  
Chinnaiyan AM, 1996, J BIOL CHEM, V271, P4573
[7]   A CONSERVED DOMAIN IN BAK, DISTINCT FROM BH1 AND BH2, MEDIATES CELL-DEATH AND PROTEIN-BINDING FUNCTIONS [J].
CHITTENDEN, T ;
FLEMINGTON, C ;
HOUGHTON, AB ;
EBB, RG ;
GALLO, GJ ;
ELANGOVAN, B ;
CHINNADURAI, G ;
LUTZ, RJ .
EMBO JOURNAL, 1995, 14 (22) :5589-5596
[8]   STRUCTURE-FUNCTION OF THE CHANNEL-FORMING COLICINS [J].
CRAMER, WA ;
HEYMANN, JB ;
SCHENDEL, SL ;
DERIY, BN ;
COHEN, FS ;
ELKINS, PA ;
STAUFFACHER, CV .
ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE, 1995, 24 :611-641
[9]  
DEJONG D, 1994, CANCER RES, V54, P256
[10]  
Ellis H.M., 1991, ANN REV CELL BIOL, V7, P663, DOI DOI 10.1146/ANNUREV.CB.07.110191.003311