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

Authors

  • Ivy K. M. Law,

    1. Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China
    2. Genome Research Center, University of Hong Kong, Hong Kong, China
    3. Research Center of Heart, Brain, Hormone, and Healthy Aging, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
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  • Ling Liu,

    1. Department of Medicine, University of Hong Kong, Hong Kong, China
    2. Research Center of Heart, Brain, Hormone, and Healthy Aging, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
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    • Co-first author.

  • Aimin Xu,

    1. Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China
    2. Department of Medicine, University of Hong Kong, Hong Kong, China
    3. Research Center of Heart, Brain, Hormone, and Healthy Aging, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
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  • Karen S. L. Lam,

    1. Department of Medicine, University of Hong Kong, Hong Kong, China
    2. Research Center of Heart, Brain, Hormone, and Healthy Aging, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
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  • Paul M. Vanhoutte,

    1. Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China
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  • Chi-Ming Che,

    1. Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong, Hong Kong, China
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  • Priscilla T. Y. Leung,

    1. Genome Research Center, University of Hong Kong, Hong Kong, China
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  • Yu Wang

    Corresponding author
    1. Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China
    2. Genome Research Center, University of Hong Kong, Hong Kong, China
    3. Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong, Hong Kong, China
    • Department of Pharmacology and Pharmacy, Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, 21 Sassoon Rd, Pokfulam, Hong Kong, China Fax: +85-2-2817-0859
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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 of sirtuins.

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