HMGB1: A novel Beclin 1-binding protein active in autophagy

Rui Kang, Kristen M. Livesey, Herbert J. Zeh, Michael T. Lotze, Daolin Tang

Research output: Contribution to journalComment/debatepeer-review

117 Scopus citations

Abstract

The autophagosome delivers damaged cytoplasmic constituents and proteins to the lysosome or to the extracellular space. Beclin 1, an essential autophagic protein, is a BH3-only protein that binds Bcl-2 anti-apoptotic family members and has a critical role in the initiation of autophagy. How the Beclin 1 complex specifically promotes autophagy remains largely unknown. We have found that high mobility group box 1 (HMGB1), a chromatin-associated nuclear protein and extracellular damage associated molecular pattern molecule (DAMP), is a novel Beclin 1-binding protein important in sustaining autophagy. HMGB1 shares considerable sequence homology with Beclin 1 in yeast, mice and human, representing an evolutionarily conserved regulatory step in early autophagosome formation. Endogenous HMGB1 competes with Bcl-2 for interaction with Beclin 1, and orients Beclin 1 to autophagosomes. Moreover, the intramolecular disulfide bridge (C23/45) of HMGB1 is required for binding to Beclin 1 and sustaining autophagy. Taken together, these findings indicate that endogenous HMGB1 functions as an autophagy effector by regulation of autophagosome formation.

Original languageEnglish (US)
Pages (from-to)1209-1211
Number of pages3
JournalAutophagy
Volume6
Issue number8
DOIs
StatePublished - Nov 16 2010

Keywords

  • Apoptosis
  • Autophagy
  • Bcl-2
  • Beclin 1
  • DAMP
  • ERK
  • HMGB1
  • MAPK
  • Redox

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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