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

Oncogene. 2008 Dec;27 Suppl 1(Suppl 1):S137-48. doi: 10.1038/onc.2009.51.


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

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adaptor Proteins, Vesicular Transport / physiology
  • Amino Acid Sequence
  • Animals
  • Apoptosis Regulatory Proteins / chemistry
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / physiology*
  • Arabidopsis Proteins / physiology
  • Autophagy / physiology*
  • Beclin-1
  • Conserved Sequence
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / metabolism
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / 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
  • Tumor Suppressor Proteins / physiology
  • Vesicular Transport Proteins / physiology


  • 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