Identification and characterization of proteins interacting with SIRT1 and SIRT3: implications in the antiaging and metabolic effects of sirtuins

Ivy Ka Man Law, Ling Liu, Aimin Xu, Karen S L Lam, Paul M. Vanhoutte, Chi-Ming Che, Priscilla T.Y. Leung, Yu Wang

Research output: Contribution to journalArticleResearchpeer-review

100 Citations (Scopus)

Abstract

Sirtuins are a family of NAD+-dependent protein deacetylases that regulate cellular functions through deacetylation of a wide range of protein targets. Overexpression of Sir2,the first gene discovered in this family, is able to extend the life span in various organisms. The anti-aging effects of human homologues of sirtuins, SIRT1-7, have also been suggested by animal and human association studies. However, the precise mechanisms whereby sirtuins exert their anti-aging effects remain elusive. In this study, we aim to identify novel interacting partners of SIRT1 and SIRT3, two human sirtuins ubiquitously expressed in many tissue types. Our results demonstrate that SIRT1 and SIRT3 are localized within different intracellular compartments, mainly nuclei and mitochondria, respectively. Using affinity purification and MALDI-TOF/TOF-MS/MS analysis, their potential interacting partners have been identified from the enriched subcellular fractions and specific interactions confirmed by co-immunoprecipitation and Western blotting experiment. Further analyses suggest that overexpression of SIRT1 or SIRT3 in HEK293 cells could induce hypoacetylation and affect the intracellular localizations and protein stabilities of their interacting partners. Taken together, the present study has identified a number of novel SIRT protein interacting partners, which might be critically involved in the anti-aging and metabolic regulatory activities ofsirtuins.

Original languageEnglish
Pages (from-to)2444-2456
Number of pages13
JournalProteomics
Volume9
Issue number9
DOIs
Publication statusPublished - May 2009
Externally publishedYes

Keywords

  • Affinity chromatography
  • Aging
  • Interaction profiling
  • Ionization time of flight mass spectrometry
  • Liquid chromatography-tan-dem mass spectrometry
  • Matrix-assisted laser desorption

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