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The Role of Bim, a Proapoptotic BH3‐Only Member of the Bcl‐2 Family, in Cell‐Death Control
Author(s) -
STRASSER ANDREAS,
PUTHALAKATH HAMSA,
BOUILLET PHILIPPE,
HUANG DAVID C.S.,
O'CONNOR LIAM,
O'REILLY LORRAINE A.,
CULLEN LEONIE,
CORY SUZANNE,
ADAMS JERRY M.
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb05419.x
Subject(s) - family member , bcl 2 family , programmed cell death , apoptosis , control (management) , chemistry , microbiology and biotechnology , medicine , biology , computer science , biochemistry , family medicine , artificial intelligence
A bstract : 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‐l‐like adapters to activate caspase zymogens, which then initiate cell degradation.