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| BID: A novel BH3 domain-only death agonist |
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| Author(s): Wang K, Yin XM, Chao DT, Milliman CL, Korsmeyer SJ |
| Source: GENES & DEVELOPMENT Volume: 10 Issue: 22 Pages: 2859-2869 Published: NOV 15 1996 |
| Times Cited: 562 References: 39 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. WASHINGTON UNIV, SCH MED, HOWARD HUGHES MED INST, DEPT MED & PATHOL, DIV MOL ONCOL, ST LOUIS, MO 63110 USA |
| Publisher: COLD SPRING HARBOR LAB PRESS, 1 BUNGTOWN RD, PLAINVIEW, NY 11724 |
| Subject Category: Cell Biology; Developmental Biology; Genetics & Heredity |
| IDS Number: VV156 |
| ISSN: 0890-9369 |
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