Constitutive association of the proapoptotic protein Bim with Bcl-2-related proteins on mitochondria in T cells.
Apoptosis in activated T cells in vivo requires the proapoptotic Bcl-2 family member Bim. We show here that, despite its ability to bind LC8, a component of the microtubule dynein motor complex, most of the Bim in both healthy and apoptotic T cells is associated with mitochondria, not microtubules. In healthy resting T cells Bim is bound to the antiapoptotic proteins Bcl-2 and Bcl-x(L). In activated T cells, levels of Bcl-2 fall, and Bim is associated more with Bcl-x(L) and less with Bcl-2. Our results indicate that, in T cells, Bim function is regulated by interaction with Bcl-2 family members on mitochondria rather than by sequestration to the microtubules.
Zhu
Yanan
Y
Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Swanson
Bradley J
BJ
Wang
Michael
M
Hildeman
David A
DA
Schaefer
Brian C
BC
Liu
Xinqi
X
Suzuki
Hiroyuki
H
Mihara
Katsuyoshi
K
Kappler
John
J
Marrack
Philippa
P
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2