Bcl-2 Localized at the Nuclear Compartment Induces Apoptosis after Transient Overexpression*
- Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas 77555-1043
- ↵1 To whom correspondence should be addressed. Tel.: 409-772-6414; Fax: 409-772-1861; E-mail: gtaglial{at}utmb.edu.
Abstract
Bcl-2 is the best characterized member of a large family of proteins that regulate apoptosis. Although it is established that Bcl-2 localized at the mitochondria functions as an anti-apoptotic protein, the function of Bcl-2 at the nucleus remains unclear. Recently we showed that nuclear compartment-associated Bcl-2 inhibits transcription factor activation. Based on this observation, we hypothesized that presence of Bcl-2 at the nucleus may induce rather than protect cells from apoptosis. Here we investigated the putative apoptotic role of nuclear compartment-associated Bcl-2. Additionally, we examined the role of the Bcl-2 BH4 domain in mediating binding to FKBP38, the Bcl-2 mitochondrial chaperone. Our results demonstrate a novel, pro-apoptotic function for nuclear Bcl-2 and identify the Bcl-2 BH4 domain as a key regulator in mediating Bcl-2/FKBP38 binding. These results indicate that Bcl-2 has a dual role as both a protector and a killer and that the ability to switch roles depends on Bcl-2 subcellular localization.
- Received June 28, 2006.
- Revision received October 13, 2006.
- The American Society for Biochemistry and Molecular Biology, Inc.
