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

Kang, Woo Kyu; Kim, Yeong Hyeock; Kang, Hyun Ah; Kwon, Ki‐Sun; Kim, Jeong‐Yoon

doi:10.7554/elife.09709

Cited by 30 publications

(41 citation statements)

References 62 publications

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“…In this case, phosphorylation of Sir2 via the cyclic AMP-PKA pathway was shown to inhibit Sir2 activity (Kang et al 2015). CR reduces PKA activity independently of NAD + or NADH.…”

Section: Caloric Restriction and Silencingmentioning

confidence: 99%

“…Indeed, Sir2 was recently reported to be modified and regulated by sumoylation and phosphorylation (Hannan et al 2015;Kang et al 2015). Sir2 is sumoylated by the SUMO ligase Siz2 on three lysines (K106, K132, and K215) within the N-terminal extension domain that associates with Sir4.…”

Section: Sir2 Post-translational Modificationsmentioning

confidence: 99%

“…Sir2 is phosphorylated on a highly-conserved Ser473 residue located within the catalytic core domain (Kang et al 2015). The modification alters the acetylation state and expression level of the PMA1 gene, where Sir2 acts to control life span.…”

Section: Sir2 Post-translational Modificationsmentioning

confidence: 99%

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The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

2016

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Transcriptional silencing in Saccharomyces cerevisiae occurs at several genomic sites including the silent mating-type loci, telomeres, and the ribosomal DNA (rDNA) tandem array. Epigenetic silencing at each of these domains is characterized by the absence of nearly all histone modifications, including most prominently the lack of histone H4 lysine 16 acetylation. In all cases, silencing requires Sir2, a highly-conserved NAD + -dependent histone deacetylase. At locations other than the rDNA, silencing also requires additional Sir proteins, Sir1, Sir3, and Sir4 that together form a repressive heterochromatin-like structure termed silent chromatin. The mechanisms of silent chromatin establishment, maintenance, and inheritance have been investigated extensively over the last 25 years, and these studies have revealed numerous paradigms for transcriptional repression, chromatin organization, and epigenetic gene regulation. Studies of Sir2-dependent silencing at the rDNA have also contributed to understanding the mechanisms for maintaining the stability of repetitive DNA and regulating replicative cell aging. The goal of this comprehensive review is to distill a wide array of biochemical, molecular genetic, cell biological, and genomics studies down to the "nuts and bolts" of silent chromatin and the processes that yield transcriptional silencing.

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“…In this case, phosphorylation of Sir2 via the cyclic AMP-PKA pathway was shown to inhibit Sir2 activity (Kang et al 2015). CR reduces PKA activity independently of NAD + or NADH.…”

Section: Caloric Restriction and Silencingmentioning

confidence: 99%

Section: Sir2 Post-translational Modificationsmentioning

confidence: 99%

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The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

2016

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“…This change in directionality is reminiscent of the change in directionality of sir2D-aging phenotypes when switching from complete minimal medium to YP medium. It will be interesting to see if the different effects of media act directly through Sir2, perhaps through NAD+ levels or phosphorylation (Kang et al 2015) to alter Sir-based Figure 8 Effect of glucose on stability of Sir-based silencing during growth on YP medium. The CRASH strain was plated on solid medium with 0.5, 2, 6, or 12% glucose and resulting colonies were imaged.…”

Section: Discussionmentioning

confidence: 99%

Nutritional Control of Chronological Aging and Heterochromatin inSaccharomyces cerevisiae

McCleary¹,

Rine

2017

Genetics

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Calorie restriction extends life span in organisms as diverse as yeast and mammals through incompletely understood mechanisms.The role of NAD + -dependent deacetylases known as Sirtuins in this process, particularly in the yeast Saccharomyces cerevisiae, is controversial. We measured chronological life span of wild-type and sir2D strains over a higher glucose range than typically used for studying yeast calorie restriction. sir2D extended life span in high glucose complete minimal medium and had little effect in low glucose medium, revealing a partial role for Sir2 in the calorie-restriction response under these conditions. Experiments performed on cells grown in rich medium with a newly developed genetic strategy revealed that sir2D shortened life span in low glucose while having little effect in high glucose, again revealing a partial role for Sir2. In complete minimal media, Sir2 shortened life span as glucose levels increased; whereas in rich media, Sir2 extended life span as glucose levels decreased. Using a genetic strategy to measure the strength of gene silencing at HML, we determined increasing glucose stabilized Sir2-based silencing during growth on complete minimal media. Conversely, increasing glucose destabilized Sir-based silencing during growth on rich media, specifically during late cell divisions. In rich medium, silencing was far less stable in high glucose than in low glucose during stationary phase. Therefore, Sir2 was involved in a response to nutrient cues including glucose that regulates chronological aging, possibly through Sir2-dependent modification of chromatin or deacetylation of a nonhistone protein.

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“…To evaluate SRT2 function, we expressed SRT1 and SRT2 in a yeast sir2 mutant (Supplemental Figure 6A), which does not survive on medium containing a high concentration of salt (Kang et al, 2015). SRT2, but not SRT1, rescued the yeast sir2 mutant salt-sensitive phenotype ( Figure 6A), indicating that SRT2 from Arabidopsis has a function similar to that of SIR2 from yeast.…”

Section: Srt2 Restores Yeast Sir2 Mutant Phenotype and Regulates H3k9mentioning

confidence: 99%

Histone Deacetylases SRT1 and SRT2 Interact with ENAP1 to Mediate Ethylene-Induced Transcriptional Repression

Zhang

Wang

et al. 2018

Plant Cell

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Ethylene plays pleiotropic roles in plant growth, plant development, and stress responses. Although the effects of ethylene on plants are well documented, little is known about molecular-level events that result in transcriptional repression during the ethylene response. In this study, we found that two histone deacetylases, SRT1 and SRT2, interact with ENAP1, which associates with EIN2 in the nucleus. Genetic and transcriptome analyses revealed that SRT1 and SRT2 are required for negative regulation of certain ethylene-responsive genes. The acetylation of HISTONE3 at K9 (H3K9Ac) is specifically regulated by SRT1 and SRT2 in ethylene-repressed genes. In addition, the srt1 srt2 double mutation in Arabidopsis thaliana suppresses both the ENAP1ox and the EIN3ox constitutive ethylene response phenotypes, and the ethylene-induced transcriptional repression observed in EIN3ox plants is derepressed in the EIN3ox/srt1 srt2 mutant. SRT2 and ENAP1 both bind to promoter regions of genes negatively regulated by ethylene, reducing H3K9Ac levels and resulting in transcriptional repression. This work establishes a mechanism by which histone deacetylases SRT1 and SRT2 interact with ENAP1 to mediate transcriptional repression by regulating the levels of H3K9 acetylation in the ethylene signaling.

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

Cited by 30 publications

References 62 publications

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

Nutritional Control of Chronological Aging and Heterochromatin inSaccharomyces cerevisiae

Histone Deacetylases SRT1 and SRT2 Interact with ENAP1 to Mediate Ethylene-Induced Transcriptional Repression

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