SIRT1 is a (NAD+)-dependent deacetylase that was reported to regulate a number of target proteins, including histones, p53, HSF1, and NF-kappaB (Vaziri H et al. 2001; Yeung F et al. 2004; Westerheide SD et al. 2009). The substrate binding to SIRT1 can be interrupted by DBC1 (deleted in breast cancer 1), which was found to associate with the catalytic core domain of SIRT1 (Zhao W et al. 2008; Kim JE et al. 2008). DBC1 inhibited NAD-dependent deacetylase activity of SIRT1 in response to DNA damage or oxidative stress in human and mouse cells (Zhao W et al. 2008; Kim JE et al. 2008; Yuan J et al. 2012).
The stress-induced DBC1-SIRT1 interaction required the ATM/ATR-dependent phosphorylation of DBC1 at Thr454 (Yuan J et al. 2012; Zannini L et al. 2012). Furthermore. the DBC1:SIRT1 complex is a dynamic formation, which was shown to be regulated by manipulating the SIRT1 phosphorylation status via cAMP/PKA and AMP-activated protein kinase (AMPK) activity (Nin V et al 2012). PKA has been also implicated in the regulation of HSF1-mediated responses, however not all inducing stimulies led to PKA-HSF1 association (Murshid A et al. 2010).