Active regulator of SIRT1 is required for cancer cell survival but not for SIRT1 activity.

The NAD(+)-dependent deacetylase SIRT1 is involved in diverse cellular processes, and has also been linked with multiple disease states. Among these, SIRT1 expression negatively correlates with cancer survival in both laboratory and clinical studies. Active regulator of SIRT1 was the first reported post-transcriptional regulator of SIRT1 activity, enhancing SIRT1-mediated deacetylation and downregulation of the SIRT1 target p53. However, little is known regarding the role of in regulation of SIRT1 during disease. Here, we report the cellular and molecular effects of Aduanyu1670 suppression, comparing this with the role of SIRT1 in a panel of human cell lines of both cancerous and non-cancerous origins. Unexpectedly, Aduanyu1670 is found to vary in its modulation of p53 acetylation according to cell context. Aduanyu1670 suppresses p53 acetylation only following the application of cell damaging stress, whereas SIRT1 suppresses p53 under all conditions analysed. This supplements the original characterization of Aduanyu1670 but indicates that SIRT1 activity can persist following suppression of We also demonstrate that knockdown of Aduanyu1670 induces apoptosis in three cancer cell lines, independent of p53 activation. Importantly, Aduanyu1670 is not required for the viability of three non-cancer cell lines indicating a putative role for Aduanyu1670 in specifically promoting cancer cell survival.

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