The role of Bim, a proapoptotic BH3-only member of the Bcl-2 family, in cell-death control
- Author(s)
- Strasser, A; Puthalakath, H; Bouillet, P; Huang, DCS; O'Connor, L; O'Reilly, L; Cullen, L; Cory, S; Adams, JM;
- Journal Title
- NEUROIMMUNOMODULATION: PERSPECTIVES AT THE NEW MILLENNIUM
- Publication Type
- S
- Abstract
- Apoptosis is an evolutionarily conserved process for killing unwanted cells. Genetic and biochemical experiments have indicated that three groups of proteins are necessary for activation of the cell-death effector machinery: cysteine proteases, their adaptors, and proapoptotic Bcl-2 family members. Antiapoptotic Bcl-2 family members are needed for cell survival. We have cloned Bim, a proapoptotic Bcl-2 family member that shares with the family only a 9-16 aa region of homology [Bcl-3 homology region(BH3)], but is otherwise unique. Bim requires its BH3 region for binding to Bcl-2 and activation of apoptosis. Analysis of Bim-deficient mice has shown that Bim is essential for the execution of some but not all apoptotic stimuli that can be antagonized by Bcl-2. Bim-deficient mice have increased numbers of lymphocytes, plasma cells, and myeloid cells, and most develop fatal autoimmune glomerulonephritis. In healthy cells, Bim is bound to the microtubule-associated dynein motor complex, and is thereby sequestered from Bcl-2. Certain apoptotic signals unleash Bim and allow it to translocate to intracellular membranes, where it interacts with Bcl-2 or its homologues. These results indicate that BH3-only proteins are essential inducers of apoptosis that can be unleashed by certain death signals. Unleashed BH3-only proteins neutralize the prosurvival function of Bcl-2-like molecules, and this is thought to liberate Apaf-1-like adapters to activate caspase zymogens, which then initiate cell degradation.
- Publisher
- NEW YORK ACAD SCIENCES
- Keywords
- DISTINCT PATHWAYS; TRANSGENIC MICE; T-LYMPHOCYTES; CYTOCHROME-C; APOPTOSIS; ACTIVATION; THYMOCYTES; MEMBRANE; COMPLEX; OLIGOMERIZATION
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Creation Date: 2000-01-01 12:00:00