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/debate

105 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Autophagy
Carrier Proteins
Proteins
Extracellular Space
Sequence Homology
Nuclear Proteins
Lysosomes
Beclin-1
Disulfides
Chromatin
Yeasts
Autophagosomes

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

HMGB1 : A novel Beclin 1-binding protein active in autophagy. / Kang, Rui; Livesey, Kristen M.; Zeh, Herbert J.; Lotze, Michael T.; Tang, Daolin.

In: Autophagy, Vol. 6, No. 8, 16.11.2010, p. 1209-1211.

Research output: Contribution to journalComment/debate

Kang, Rui ; Livesey, Kristen M. ; Zeh, Herbert J. ; Lotze, Michael T. ; Tang, Daolin. / HMGB1 : A novel Beclin 1-binding protein active in autophagy. In: Autophagy. 2010 ; Vol. 6, No. 8. pp. 1209-1211.
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