Comparative interactomes of SIRT6 and SIRT7: Implication of functional links to aging

Sirtuins are NAD + ‐dependent deacetylases that regulate a range of cellular processes. Although diverse functions of sirtuins have been proposed, those functions of SIRT 6 and SIRT 7 that are mediated by their interacting proteins remain elusive. In the present study, we identified SIRT 6‐ and SIRT 7‐interacting proteins, and compared their interactomes to investigate functional links. Our interactomes revealed 136 interacting proteins for SIRT 6 and 233 for SIRT 7 while confirming seven and 111 proteins identified previously for SIRT 6 and SIRT 7, respectively. Comparison of SIRT 6 and SIRT 7 interactomes under the same experimental conditions disclosed 111 shared proteins, implying related functional links. The interaction networks of interactomes indicated biological processes associated with DNA repair, chromatin assembly, and aging. Interactions of two highly acetylated proteins, nucleophosmin ( NPM 1) and nucleolin, with SIRT 6 and SIRT 7 were confirmed by co‐immunoprecipitation. NPM 1 was found to be deacetylated by both SIRT 6 and SIRT 7. In senescent cells, the acetylation level of NPM 1 was increased in conjunction with decreased levels of SIRT 6 and SIRT 7, suggesting that the acetylation of NPM 1 could be regulated by SIRT 6 and SIRT 7 in the aging process. Our comparative interactomic study of SIRT 6 and SIRT 7 implies important functional links to aging by their associations with interacting proteins. All MS data have been deposited in the ProteomeXchange with identifiers PXD000159 and PXD000850 ( http://proteomecentral.proteomexchange.org/dataset/PXD000159 , http://proteomecentral.proteomexchange.org/dataset/PXD000850 ).