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Originally published In Press as doi:10.1074/jbc.M104073200 on August 8, 2001

J. Biol. Chem., Vol. 276, Issue 41, 37754-37760, October 12, 2001
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BH3-only Bcl-2 Family Members Are Coordinately Regulated by the JNK Pathway and Require Bax to Induce Apoptosis in Neurons*

Charles A. HarrisDagger and Eugene M. Johnson Jr.Dagger §

From the Departments of Dagger  Molecular Biology and Pharmacology and § Neurology, Washington University School of Medicine, St. Louis, Missouri 63110

The Bcl-2 family of proteins are key regulators of programmed cell death. A distinct subfamily of BH3-only molecules has been identified, but their exact mechanism of action remains unclear. Here we show that the BH3-only Bcl-2 family members, Dp5/Hrk and Bim, are induced upstream of the Bax checkpoint in neuronal apoptosis in a manner that shows significant dependence on JNK signaling. We also show that Dp5 and other BH3-only proteins kill cerebellar granule neurons in a Bax-dependent manner. These studies demonstrate that BH3-only members do not act independently in their proapoptotic activities but rather require the action of multidomain proapoptotic Bcl-2 family members to produce cell death.

* This work was supported by National Institutes of Health Grants AG12947 and NS38651 (to E. M. J.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Molecular Biology and Pharmacology, Washington University School of Medicine, 4566 Scott Ave., Box 8103, Saint Louis, Missouri 63110. Tel.: 314-362-3926; Fax: 314-747-1772; E-mail: ejohnson@pcg.wustl.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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