Continuing with yesterday’s sirtuin and aging theme, here are three more recent papers that further expand the Sirt1/aging literature. Two pertain to regulation of Sirt1 expression, and the third to Sirt1’s regulation of a hormone signaling axis relevant to cancer.
Regulation of Sirt1 by CD38: Regulation of SIRT 1 mediated NAD dependent deacetylation: A novel role for the multifunctional enzyme CD38, Askoy et al.:
… Here, we investigate the modulation of the SIRT 1 activity by CD38. We propose that by modulating availability of NAD to the SIRT1 enzyme, CD38 may regulate SIRT1 enzymatic activity. We observed that in CD38 knockout mice, tissue levels of NAD are significantly increased. We also observed that incubation of purified recombinant SIRT1 enzyme with CD38 or nuclear extracts of wild-type mice led to a significant inhibition of its activity. In contrast, incubation of SIRT1 with cellular extract from CD38 knockout mice was without effect. …
Regulation by E2F1 (plus an apoptosis connection): Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage, Wang et al.:
… This report shows that the cell-cycle and apoptosis regulator E2F1 induces SirT1 expression at the transcriptional level. Furthermore, SirT1 binds to E2F1 and inhibits E2F1 activities, forming a negative feedback loop. Knockdown of SirT1 by small interference RNA (siRNA) increases E2F1 transcriptional and apoptotic functions. … These results reveal a mutual regulation between E2F1 and SirT1 that affects cellular sensitivity to DNA damage.
Regulation of hormone signaling: The Hormonal Control of Androgen Receptor Function through SIRT1, Fu et al.:
…SIRT1 antagonists induce endogenous AR expression and enhance DHT-mediated AR expression. … hSIRT1 repression of DHT-induced AR signaling requires the NAD-dependent catalytic function of hSIRT1 and the AR lysine residues deacetylated by SIRT1. SIRT1 inhibited co-activator induced interactions between the AR-amino and carboxyl termini. DHT-induced prostate cancer cellular contact-independent growth is also blocked by SIRT1, providing a direct functional link between the AR, which is a critical determinant of progression of human prostate cancer, and the sirtuins.