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

Abstract

Sirtuins are NAD(+) -dependent deacetylases that regulate a range of cellular

processes. Although diverse functions of sirtuins have been proposed, those

functions of SIRT6 and SIRT7 that are mediated by their interacting proteins

remain elusive. In the present study, we identified SIRT6- and SIRT7-interacting

proteins, and compared their interactomes to investigate functional links. Our

interactomes revealed 136 interacting proteins for SIRT6 and 233 for SIRT7 while

confirming seven and 111 proteins identified previously for SIRT6 and SIRT7,

respectively. Comparison of SIRT6 and SIRT7 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 (NPM1) and nucleolin, with SIRT6

and SIRT7 were confirmed by co-immunoprecipitation. NPM1 was found to be

deacetylated by both SIRT6 and SIRT7. In senescent cells, the acetylation level

of NPM1 was increased in conjunction with decreased levels of SIRT6 and SIRT7,

suggesting that the acetylation of NPM1 could be regulated by SIRT6 and SIRT7 in

the aging process. Our comparative interactomic study of SIRT6 and SIRT7 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).