Constitutive association of the proapoptotic protein Bim with Bcl-2-related proteins on mitochondria in T cells

Yanan Zhu, Bradley Jay Swanson, Michael Wang, David A. Hildeman, Brian C. Schaefer, Xinqi Liu, Hiroyuki Suzuki, Katsuyoshi Mihara, John W. Kappler, Philippa Marrack

Proceedings of the National Academy of Sciences · 2004 · 127 citations · 41 references

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Abstract

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.

References

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