Abstract
BH3 domains were originally discovered in the context of apoptosis regulators and they mediate binding of proapoptotic Bcl-2 family members to antiapoptotic Bcl-2 family members. Yet, recent studies indicate that BH3 domains do not function uniquely in apoptosis regulation; they also function in the regulation of another critical pathway involved in cellular and tissue homeostasis called autophagy. Antiapoptotic Bcl-2 homologs downregulate autophagy through interactions with the essential autophagy effector and haploinsufficient tumor suppressor, Beclin 1. Beclin 1 contains a BH3 domain, similar to that of Bcl-2 proteins, which is necessary and sufficient for binding to antiapoptotic Bcl-2 homologs and required for Bcl-2-mediated inhibition of autophagy. This review will summarize the evidence that the BH3 domain of Beclin 1 serves as a key structural motif that enables Bcl-2 to function not only as an antiapoptotic protein, but also as an antiautophagy protein.
Original language | English (US) |
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Pages (from-to) | S137-S148 |
Journal | Oncogene |
Volume | 27 |
DOIs | |
State | Published - Dec 2008 |
Keywords
- Apoptosis
- Autophagy
- BH3-only
- Bcl-2
- Beclin 1
- Tumor suppressor
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research