The autophagy effector Beclin 1: a novel BH3-only protein.
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.
Sinha
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Department of Chemistry, Biochemistry and Molecular Biology, North Dakota State University, Fargo, ND, USA. Sangita.Sinha@ndsu.edu
Levine
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B
D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D029681:Arabidopsis Proteins / Q000502:physiology; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D017124:Conserved Sequence; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000502:physiology
D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; D029681:Arabidopsis Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; C402377:VPS30 protein, S cerevisiae; D033921:Vesicular Transport Proteins; C519561:beclin 1 protein, Arabidopsis