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Sci. Signal., 25 August 2009
Vol. 2, Issue 85, p. ra48
[DOI: 10.1126/scisignal.2000274]

RESEARCH ARTICLES

The VDAC2-BAK Rheostat Controls Thymocyte Survival

Decheng Ren1, Hyungjin Kim1, Ho-Chou Tu1, Todd D. Westergard1, Jill K. Fisher2, Jeff A. Rubens2, Stanley J. Korsmeyer2*, James J.-D. Hsieh1, and Emily H.-Y. Cheng1,3{dagger}

1 Molecular Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
2 Dana-Farber Cancer Institute, Boston, MA 02115, USA.
3 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

* Deceased.

Abstract: The proapoptotic proteins BAX and BAK constitute the mitochondrial apoptotic gateway that executes cellular demise after integrating death signals. The lethal BAK is kept in check by voltage-dependent anion channel 2 (VDAC2), a mammalian-restricted VDAC isoform. Here, we provide evidence showing a critical role for the VADC2-BAK complex in determining thymocyte survival in vivo. Genetic depletion of Vdac2 in the thymus resulted in excessive cell death and hypersensitivity to diverse death stimuli including engagement of the T cell receptor. These phenotypes were completely rescued by the concurrent deletion of Bak but not that of Bax. Thus, the VDAC2-BAK axis provides a mechanism that governs the homeostasis of thymocytes. Our study reveals a sophisticated built-in rheostat that likely fine-tunes immune competence to balance autoimmunity and immunodeficiency.

{dagger} To whom correspondence should be addressed. E-mail: echeng{at}dom.wustl.edu

Citation: D. Ren, H. Kim, H.-C. Tu, T. D. Westergard, J. K. Fisher, J. A. Rubens, S. J. Korsmeyer, J. J.-D. Hsieh, E. H.-Y. Cheng, The VDAC2-BAK Rheostat Controls Thymocyte Survival. Sci. Signal. 2, ra48 (2009).

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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M. Lazarou, D. Stojanovski, A. E. Frazier, A. Kotevski, G. Dewson, W. J. Craigen, R. M. Kluck, D. L. Vaux, and M. T. Ryan (2010)
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