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The autophagy effector Beclin 1: a novel BH3-only protein

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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.

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Acknowledgements

The work in the authors’ laboratory was funded by NIH Grants R21 AI78108-01 to SS and RO1 CA109618 and R01 CA084254 to BL.

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Authors and Affiliations

  1. Department of Chemistry, Biochemistry and Molecular Biology, North Dakota State University, Fargo, ND, USA

    S Sinha

  2. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

    B Levine

  3. Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    B Levine

  4. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA

    B Levine

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Sinha, S., Levine, B. The autophagy effector Beclin 1: a novel BH3-only protein. Oncogene 27 (Suppl 1), S137–S148 (2008). https://doi.org/10.1038/onc.2009.51

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