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Sir2 phosphorylation through cAMP-PKA and CK2 signaling inhibits the lifespan extension activity of Sir2 in yeast

  1. Woo Kyu Kang
  2. Yeong Hyeock Kim
  3. Hyun Ah Kang
  4. Ki-Sun Kwon
  5. Jeong-Yoon Kim  Is a corresponding author
  1. Chungnam National University, Republic of Korea
  2. Chung-Ang University, Republic of Korea
  3. Korea Research Institute of Bioscience and Biotechnology, Republic of Korea
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Cite this article as: eLife 2015;4:e09709 doi: 10.7554/eLife.09709

Abstract

Sir2, an NAD+-dependent protein deacetylase, has been proposed to be a longevity factor that plays important roles in dietary restriction (DR)-mediated lifespan extension. Here we show that the Sir2's role for DR-mediated lifespan extension depends on cAMP-PKA and casein kinase 2 (CK2) signaling in yeast. Sir2 partially represses the transcription of lifespan-associated genes, such as PMA1 (encoding an H+-ATPase) and many ribosomal protein genes, through deacetylation of Lys 16 of histone H4 in the promoter regions of these genes. This repression is relieved by Sir2 S473 phosphorylation, which is mediated by active cAMP-PKA and CK2 signaling. Moderate DR increases the replicative lifespan of wild-type yeast but has no effect on that of yeast expressing the Sir2 S473E or S473A allele, suggesting that the effect of Sir2 on DR-mediated lifespan extension is negatively regulated by S473 phosphorylation. Our results demonstrate a novel mechanism by which Sir2 contributes to lifespan extension.

Article and author information

Author details

  1. Woo Kyu Kang

    Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  2. Yeong Hyeock Kim

    Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  3. Hyun Ah Kang

    Department of Life Science, Chung-Ang University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  4. Ki-Sun Kwon

    Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  5. Jeong-Yoon Kim

    Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of Korea
    For correspondence
    jykim@cnu.ac.kr
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Jessica K Tyler, University of Texas MD Anderson Cancer Center, United States

Publication history

  1. Received: June 26, 2015
  2. Accepted: September 2, 2015
  3. Accepted Manuscript published: September 2, 2015 (version 1)
  4. Version of Record published: September 29, 2015 (version 2)

Copyright

© 2015, Kang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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