Abstract
SIRT1 regulates a variety of cellular functions, including cellular stress responses and energy metabolism. SIRT1 activity is negatively regulated by DBC1 (Deleted in Breast Cancer 1) through direct binding. However, how the DBC1-SIRT1 interaction is regulated remains unclear. We found that the DBC1-SIRT1 interaction increases following DNA damage and oxidative stress. The stress-induced DBC1-SIRT1 interaction requires the ATM-dependent phosphorylation of DBC1 at Thr 454, which creates a second binding site for SIRT1. Finally, we showed that the stress-induced DBC1-SIRT1 interaction is important for cell fate determination following genotoxic stress. These results revealed a novel mechanism of SIRT1 regulation during genotoxic stress.
Original language | English (US) |
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Pages (from-to) | 791-796 |
Number of pages | 6 |
Journal | Genes and Development |
Volume | 26 |
Issue number | 8 |
DOIs | |
State | Published - 2012 |
Keywords
- Apoptosis
- DBC1
- Genotoxic stress
- Phosphorylation
- SIRT1
ASJC Scopus subject areas
- General Medicine