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.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Adaptor Proteins, Vesicular Transport / physiology
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Amino Acid Sequence
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Animals
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Apoptosis Regulatory Proteins / chemistry
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / physiology*
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Arabidopsis Proteins / physiology
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Autophagy / physiology*
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Beclin-1
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Conserved Sequence
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Eukaryotic Cells / cytology
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Eukaryotic Cells / metabolism
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Humans
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Membrane Proteins / chemistry
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Membrane Proteins / physiology*
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Mice
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Models, Molecular
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Molecular Sequence Data
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Protein Conformation
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Protein Interaction Mapping
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Saccharomyces cerevisiae Proteins / physiology
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Sequence Alignment
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Sequence Homology, Amino Acid
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Signal Transduction / physiology
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Structure-Activity Relationship
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Tumor Suppressor Proteins / chemistry
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Tumor Suppressor Proteins / physiology
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Vesicular Transport Proteins / physiology
Substances
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Adaptor Proteins, Vesicular Transport
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Apoptosis Regulatory Proteins
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Arabidopsis Proteins
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BECN1 protein, human
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Beclin-1
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Becn1 protein, mouse
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Membrane Proteins
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Proto-Oncogene Proteins c-bcl-2
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Saccharomyces cerevisiae Proteins
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Tumor Suppressor Proteins
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VPS30 protein, S cerevisiae
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Vesicular Transport Proteins
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beclin 1 protein, Arabidopsis