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 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).
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
Namgyu
N
Lee
Dae-Kyum
DK
Kim
Eung-Sam
ES
Kim
Sung Jin
SJ
Park
Jung-Hee
JH
Kwon
Jihye
J
Shin
Seon-Min
SM
Park
Young Ho
YH
Moon
Hee Jung
HJ
Wang
Yong Song
YS
Gho
Kwan Yong
KY
Choi
D000107:Acetylation; D000375:Aging; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism; D000090243:Nucleophosmin; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods; D016601:RNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D037761:Sirtuins / Q000032:analysis / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods; D000097796:Nucleolin
D009687:Nuclear Proteins; D000090243:Nucleophosmin; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D037761:Sirtuins; D000097796:Nucleolin; C000716967:NPM1 protein, human; C510661:SIRT7 protein, human; C516592:SIRT6 protein, human
Aging; Cell biology; ESI-MS/MS; Interaction profiling