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 language | English (US) |
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Pages (from-to) | 1209-1211 |
Number of pages | 3 |
Journal | Autophagy |
Volume | 6 |
Issue number | 8 |
DOIs |
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State | Published - Nov 16 2010 |
Externally published | Yes |
Keywords
- Apoptosis
- Autophagy
- Bcl-2
- Beclin 1
- DAMP
- ERK
- HMGB1
- MAPK
- Redox
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology