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PMID: 19641499 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

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

Oncogene ·Vol. 27 Suppl 1 ·2008-12-00 ·Pages S137-48

Sinha S, Levine B

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.

MeSH Terms
Adaptor Proteins, Vesicular Transport/physiology Amino Acid Sequence Animals Apoptosis Regulatory Proteins/chemistry,genetics,physiology Arabidopsis Proteins/physiology Autophagy/physiology Beclin-1 Conserved Sequence Eukaryotic Cells/cytology,metabolism Humans Membrane Proteins/chemistry,physiology Mice Models, Molecular Molecular Sequence Data Protein Conformation Protein Interaction Mapping Protein Structure, Tertiary Proto-Oncogene Proteins c-bcl-2/metabolism Saccharomyces cerevisiae Proteins/physiology Sequence Alignment Sequence Homology, Amino Acid Signal Transduction/physiology Structure-Activity Relationship Tumor Suppressor Proteins/chemistry,physiology Vesicular Transport Proteins/physiology
Chemicals
Adaptor Proteins, Vesicular Transport Apoptosis Regulatory Proteins Arabidopsis Proteins BECN1 protein, human Beclin-1 Becn1 protein, mouse Membrane Proteins Proto-Oncogene Proteins c-bcl-2 Saccharomyces cerevisiae Proteins Tumor Suppressor Proteins VPS30 protein, S cerevisiae Vesicular Transport Proteins beclin 1 protein, Arabidopsis
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sinha S
Department of Chemistry, Biochemistry and Molecular Biology, North Dakota State University, Fargo, ND, USA. Sangita.Sinha@ndsu.edu
Levine B
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Article Info
Journal
Oncogene
Abbr.
Oncogene
ISSN
1476-5594
DOI
10.1038/onc.2009.51
Email
sangita.sinha@ndsu.edu
Published
2008-12-00
Pages
S137-48
Language
English
Region
England
NLM ID
8711562
PMCID
PMC2731580
Subset
IM
Grants
NIAID NIH HHS · R21 AI078108-01 · United States
NCI NIH HHS · R01 CA084254-10 · United States
NIAID NIH HHS · R21 AI78108-01 · United States
NCI NIH HHS · R01 CA084254 · United States
NIAID NIH HHS · R21 AI078108 · United States
Howard Hughes Medical Institute · United States
NCI NIH HHS · R01 CA109618-05 · United States
NCI NIH HHS · R01 CA109618 · United States
External Links
PubMed source DOI: 10.1038/onc.2009.51 PMC Full Text View journal details
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