Regulation of SIRT1 activity by genotoxic stress

Jian Yuan, Kuntian Luo, Tongzheng Liu, Zhenkun Lou

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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 languageEnglish (US)
Pages (from-to)791-796
Number of pages6
JournalGenes and Development
Volume26
Issue number8
DOIs
StatePublished - 2012

Keywords

  • Apoptosis
  • DBC1
  • Genotoxic stress
  • Phosphorylation
  • SIRT1

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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