Sir2 phosphorylation through cAMP-PKA and CK2 signaling inhibits the lifespan extension activity of Sir2 in yeast
Silent information regulator 2 (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. In this study, we show that the Sir2's role for DR-mediated lifespan extension depends on...
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doaj-77b5896502c34a2e9ec9e24e164c88f32021-05-04T23:59:55ZengeLife Sciences Publications LtdeLife2050-084X2015-09-01410.7554/eLife.09709Sir2 phosphorylation through cAMP-PKA and CK2 signaling inhibits the lifespan extension activity of Sir2 in yeastWoo Kyu Kang0Yeong Hyeock Kim1Hyun Ah Kang2Ki-Sun Kwon3Jeong-Yoon Kim4Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of KoreaDepartment of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of KoreaDepartment of Life Science, Chung-Ang University, Seoul, Republic of KoreaAging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of KoreaDepartment of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of KoreaSilent information regulator 2 (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. In this study, 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 mechanism by which Sir2 contributes to lifespan extension.https://elifesciences.org/articles/09709Sir2lifespan extensiondietary restrictioncAMP-PKACK2phosphorylation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Woo Kyu Kang Yeong Hyeock Kim Hyun Ah Kang Ki-Sun Kwon Jeong-Yoon Kim |
spellingShingle |
Woo Kyu Kang Yeong Hyeock Kim Hyun Ah Kang Ki-Sun Kwon Jeong-Yoon Kim Sir2 phosphorylation through cAMP-PKA and CK2 signaling inhibits the lifespan extension activity of Sir2 in yeast eLife Sir2 lifespan extension dietary restriction cAMP-PKA CK2 phosphorylation |
author_facet |
Woo Kyu Kang Yeong Hyeock Kim Hyun Ah Kang Ki-Sun Kwon Jeong-Yoon Kim |
author_sort |
Woo Kyu Kang |
title |
Sir2 phosphorylation through cAMP-PKA and CK2 signaling inhibits the lifespan extension activity of Sir2 in yeast |
title_short |
Sir2 phosphorylation through cAMP-PKA and CK2 signaling inhibits the lifespan extension activity of Sir2 in yeast |
title_full |
Sir2 phosphorylation through cAMP-PKA and CK2 signaling inhibits the lifespan extension activity of Sir2 in yeast |
title_fullStr |
Sir2 phosphorylation through cAMP-PKA and CK2 signaling inhibits the lifespan extension activity of Sir2 in yeast |
title_full_unstemmed |
Sir2 phosphorylation through cAMP-PKA and CK2 signaling inhibits the lifespan extension activity of Sir2 in yeast |
title_sort |
sir2 phosphorylation through camp-pka and ck2 signaling inhibits the lifespan extension activity of sir2 in yeast |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2015-09-01 |
description |
Silent information regulator 2 (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. In this study, 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 mechanism by which Sir2 contributes to lifespan extension. |
topic |
Sir2 lifespan extension dietary restriction cAMP-PKA CK2 phosphorylation |
url |
https://elifesciences.org/articles/09709 |
work_keys_str_mv |
AT wookyukang sir2phosphorylationthroughcamppkaandck2signalinginhibitsthelifespanextensionactivityofsir2inyeast AT yeonghyeockkim sir2phosphorylationthroughcamppkaandck2signalinginhibitsthelifespanextensionactivityofsir2inyeast AT hyunahkang sir2phosphorylationthroughcamppkaandck2signalinginhibitsthelifespanextensionactivityofsir2inyeast AT kisunkwon sir2phosphorylationthroughcamppkaandck2signalinginhibitsthelifespanextensionactivityofsir2inyeast AT jeongyoonkim sir2phosphorylationthroughcamppkaandck2signalinginhibitsthelifespanextensionactivityofsir2inyeast |
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