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Papers In Press, published online ahead of print August 8, 2001
Molecular Biology & Pharmacology, Washington University School of Medicine, Saint Louis, MO 63110-1095
Corresponding Author: ejohnson{at}pcg.wustl.edu
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 pro-apoptotic activities, but rather require the action of multi-domain pro-apoptotic Bcl-2 family members to produce cell death.
J. Biol. Chem, 10.1074/jbc.M104073200
Submitted on May 7, 2001
Revised on July 23, 2001
Accepted on August 7, 2001
BH3-only Bcl-2 family members are coordinately regulated by the JNK pathway and require Bax to induce apoptosis in neurons
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