Sirtuins are NAD+-dependent deacetylases that regulate a range of cellular processes. Although anti-aging effects of sirtuins have been proposed, the proteins interacting with SIRT6 and SIRT7 remain elusive. In the current study, we identified SIRT6- and SIRT7-interacting proteins and compared their interactomes. Our data revealed 129 novel interacting proteins for SIRT6 and 122 for SIRT7 while confirming 7 and 111 previously identified proteins for SIRT6 and SIRT7, respectively. Comparison of the SIRT6 and SIRT7 interactomes under a same experimental condition disclosed 111 shared proteins indicated that functional associations. The functional networks of interactomes exhibited that the binding partners are associated with important biological processes in aging and age-related diseases including cancer. Two proteins, NPM1 and NCL localized in the nucleus and interacted with SIRT6 and SIRT7. NPM1 was identified as a novel substrate and its acetylation level decreased by both SIRT6 and SIRT7. Additionally, in senescent cells, the acetylation level of NPM1 was increased in conjunction with decreased level of SIRT6 and SIRT7, suggesting that acetylation of NPM1 is regulated by SIRT6 and SIRT7 in the aging process. Our findings provide insights on functional relationship between SIRT6 and SIRT7 as well as their roles in DNA repair, chromatin assembly and cancer cell proliferation, and aging.

Citation Format: Namgyu Lee, Jung-Hee Kwon, Sung Jin Park, Kwan Yong Choi. Comparative studies on SIRT6 and SIRT7 interactomes: Implications of important roles in cancer via associating with interacting partners. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 351. doi:10.1158/1538-7445.AM2014-351