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

ELife
Woo Kyu KangJeong-Yoon Kim

Abstract

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.

References

Jan 15, 1997·Genes & Development·J S Smith, J D Boeke
Jan 15, 1998·Cell·D A Sinclair, L Guarente
Mar 19, 1999·Molecular and Cellular Biology·A S ClarkeL Pillus
Mar 15, 2001·Current Opinion in Cell Biology·D Moazed
Mar 1, 2003·Science·Hugo AguilaniuThomas Nyström
Aug 9, 2003·The Journal of Biological Chemistry·Alaric A Falcón, John P Aris
Jan 16, 2004·Genes & Development·Su-Ju LinLeonard Guarente
Aug 26, 2004·PLoS Biology·Matt KaeberleinBrian K Kennedy
Nov 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Blanka Rogina, Stephen L Helfand
Nov 11, 2005·Mechanisms of Ageing and Development·Yamei Wang, Heidi A Tissenbaum
Nov 16, 2005·Cell·Paola FabrizioValter D Longo
Jan 7, 2006·Nucleic Acids Research·Joel D NelsonKarol Bomsztyk
Mar 18, 2006·Genes & Development·Michael-Christopher KeoghStephen Buratowski
Jul 29, 2006·Cell·Valter D Longo, Brian K Kennedy
Nov 14, 2006·Aging Cell·Garrick D LeeSige Zou
Nov 30, 2006·Molecular Systems Biology·Alexander M TsankovJason M Casolari
Jun 22, 2007·Proceedings of the National Academy of Sciences of the United States of America·Nika Erjavec, Thomas Nyström
Feb 25, 2009·Biochemical and Biophysical Research Communications·Barbara Zschoernig, Ulrich Mahlknecht
Jun 12, 2009·Nature·Weiwei DangShelley L Berger
Sep 11, 2010·The Journal of Biological Chemistry·Hirokazu ItoHirofumi Aiba
Sep 13, 2011·Nucleic Acids Research·Franziska HeiseAnn E Ehrenhofer-Murray
Sep 23, 2011·Nature·Mohan Viswanathan, Leonard Guarente

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Citations

Feb 5, 2016·Molecular and Biochemical Parasitology·Elena Jimenez-RuizMarkus Meissner
Aug 16, 2016·Genetics·Marc R Gartenberg, Jeffrey S Smith
May 26, 2020·Aging Cell·Mayur Nimbadas DevareJeong-Yoon Kim
Mar 28, 2019·Frontiers in Genetics·Diego Molina-SerranoAntonis Kirmizis
Jun 13, 2020·Biomolecules·Rashmi DahiyaMd Imtaiyaz Hassan

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Methods Mentioned

BETA
ChIP
acetylation
immunoprecipitation
PCR

Software Mentioned

ImageJ

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