Acetylation of Yeast AMPK Controls Intrinsic Aging Independently of Caloric Restriction

Lu, Jin; Yang, Lin; Sheu, Jin‐Chuan; Wu, June‐Tai; Lee, Fang‐Jen S.; Chen, Yue; Lin, Min I.; Chiang, Fu-Tien; Tai, Tong Yuan; Berger, Shelley L.; Zhao, Yingming; Tsai, Keh–Sung; Zhu, Heng; Chuang, Lee‐Ming; Boeke, Jef D.

doi:10.1016/j.cell.2011.07.044

Cited by 137 publications

(172 citation statements)

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“…However, none of these suppressors could bypass the need for ESA1. There has been some discussion about whether Esa1's catalytic activity is its essential function (Smith et al 1998;Decker et al 2008), and there is structural and proteomic evidence that auto-acetylation and acetylation of nonhistone substrates are major contributors in the requirement for Esa1 (Yan et al 2002;Lin et al 2009;Lu et al 2011;Yi et al 2012). Our observation that the lethality of esa1D can be bypassed by the loss of a single HDAC complex supports the idea that ESA1's essential function is its catalytic activity.…”

Section: Discussionsupporting

confidence: 72%

“…Viability of the esa1Δ sds3Δ strain added emphasis to previous data implicating a significant functional relationship between Esa1 and Rpd3 (Biswas et al 2008;Chang and Pillus 2009;Lu et al 2011;Yi et al 2012). The best-studied nonhistone targets of Esa1 are also deacetylated by Rpd3 (Lin et al 2008;Lu et al 2011;Yi et al 2012), suggesting that these substrates may be part of an extreme acetylation imbalance that leads to death in esa1Δ cells.…”

Section: Discussionmentioning

confidence: 99%

“…Rpd3 has been directly identified as the deacetylase for some histone and nonhistone targets of Esa1 (Lu et al 2011;Rando and Winston 2012;Yi et al 2012), whereas genetic interaction networks point to deletion of HDA1 as the most prominent alleviating hub for NuA4 (Lin et al 2008). Hda1 also has some overlapping functions with Rpd3 (Bernstein et al 2000;Robyr et al 2002).…”

mentioning

confidence: 99%

“…It plays a crucial role in cell cycle progression and ribosomal DNA (rDNA) silencing (Clarke et al 1999(Clarke et al , 2006 and is recruited to DNA double-strand breaks (DSBs) to promote damage repair by acetylating H4, an important step in the repair pathway (Bird et al 2002;Tamburini and Tyler 2005). Esa1 also regulates replicative life span and autophagy by acetylating the nonhistone targets Sip2 (regulatory subunit of the Snf1 complex, the yeast AMPactivated protein kinase, or AMPK) (Lu et al 2011) and Atg3 (autophagy signaling component) (Yi et al 2012). Due to Esa1's essential nature, to date, hypomorphic and conditional ESA1 alleles have been critical tools in defining its functions (Clarke et al 1999;Decker et al 2008;Lin et al 2008;Mitchell et al 2008Mitchell et al , 2011.…”

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confidence: 99%

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Bypassing the Requirement for an Essential MYST Acetyltransferase

Torres-Machorro

Pillus

2014

Genetics

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Histone acetylation is a key regulatory feature for chromatin that is established by opposing enzymatic activities of lysine acetyltransferases (KATs/HATs) and deacetylases (KDACs/HDACs). Esa1, like its human homolog Tip60, is an essential MYST family enzyme that acetylates histones H4 and H2A and other nonhistone substrates. Here we report that the essential requirement for ESA1 in Saccharomyces cerevisiae can be bypassed upon loss of Sds3, a noncatalytic subunit of the Rpd3L deacetylase complex. By studying the esa1Δ sds3Δ strain, we conclude that the essential function of Esa1 is in promoting the cellular balance of acetylation. We demonstrate this by fine-tuning acetylation through modulation of HDACs and the histone tails themselves. Functional interactions between Esa1 and HDACs of class I, class II, and the Sirtuin family define specific roles of these opposing activities in cellular viability, fitness, and response to stress. The fact that both increased and decreased expression of the ESA1 homolog TIP60 has cancer associations in humans underscores just how important the balance of its activity is likely to be for human well-being.T HE genetic information of DNA is packed into chromatin, which is predominantly composed of the H3, H4, H2A, and H2B core histone proteins that together with DNA form nucleosomes, the basic subunits of the genome (Kornberg and Lorch 1999). Chromatin structure regulates many cellular processes including gene expression, DNA replication, DNA damage repair, and recombination (Felsenfeld and Groudine 2003). Nucleosomes themselves are tightly regulated by mobilization and positioning that are mediated by ATP-dependent chromatin-remodeling machines (Rando and Winston 2012) and by multiple types of histone posttranslational modifications that include acetylation and many other marks (Campos and Reinberg 2009).Nucleosome acetylation is a highly dynamic modification that is promoted by HATs and removed by HDACs. HATs are classified by sequence into different families (Allis et al. 2007). ESA1/KAT5 belongs to the widely conserved MYST HAT family, named for its founding members (MOZ-YBF2/ SAS3-SAS2-TIP60) (Lafon et al. 2007). Esa1 is an essential HAT in yeast (Smith et al. 1998;Clarke et al. 1999) and the catalytic subunit of two distinct multi-protein complexes: NuA4 and Piccolo (Boudreault et al. 2003). Notably, the human homolog of Esa1 is Tip60, which is also essential in vertebrates and has been linked to multiple human diseases (Squatrito et al. 2006;Avvakumov and Côté 2007;Lafon et al. 2007), thus increasing the relevance of gaining a deeper understanding of essential HAT functions.Esa1 primarily acetylates H4 and H2A in vivo (Clarke et al. 1999;Lin et al. 2008) and regulates the expression of active protein-encoding genes (Reid et al. 2000;Lin et al. 2008). It plays a crucial role in cell cycle progression and ribosomal DNA (rDNA) silencing (Clarke et al. 1999(Clarke et al. , 2006 and is recruited to DNA double-strand breaks (DSBs) to promote damage repair by acetylati...

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Bypassing the Requirement for an Essential MYST Acetyltransferase

Torres-Machorro

Pillus

2014

Genetics

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“…Further layers of regulatory finesse include the reversible physical allosteric association between the ␣ and ␥ regulatory subunits and the nuclear translocation of the active trimeric complex to alter gene expression that aims to preserve the energy balance of the cell (10,20,22). Also conserved is acetylation and ubiquitination, recently reported for both mammalian AMPK and yeast SNF1 kinase complexes (23)(24)(25)(26), that appear to have inhibitory roles in regulation of the kinase. Similarly, SUMOylation has been shown to be a negative regulator of Snf1 (27), clearly adding to the complexity of regulation of this central energy-sensing switch.…”

mentioning

confidence: 99%

The SNF1 Kinase Ubiquitin-associated Domain Restrains Its Activation, Activity, and the Yeast Life Span

Jiao¹,

Postnikoff²,

Harkness³

et al. 2015

Journal of Biological Chemistry

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Background:The UBA domain in the AMP kinase family is poorly defined. Results: This motif restrains kinase activity, resulting in decreased life span and oxidative stress resistance. Conclusion: This inhibitory domain has defined influences with FOXOs on stress and aging. Significance: The overactive kinase created by UBA mutations has positive stress resistance and aging influences that may translate to human metabolic benefits.

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Overview of Protein Microarrays

et al. 2013

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Protein microarray is an emerging technology that provides a versatile platform for characterization of hundreds of thousands of proteins in a highly parallel and high-throughput way. Two major classes of protein microarrays are defined to describe their applications: analytical and functional protein microarrays. In addition, tissue or cell lysates can also be fractionated and spotted on a slide to form a reverse-phase protein microarray. While the fabrication technology is maturing, applications of protein microarrays, especially functional protein microarrays, have flourished during the past decade. Here, we will first review recent advances in the protein microarray technologies, and then present a series of examples to illustrate the applications of analytical and functional protein microarrays in both basic and clinical research. The research areas will include detection of various binding properties of proteins, study of protein posttranslational modifications, analysis of host-microbe interactions, profiling antibody specificity, and identification of biomarkers in autoimmune diseases. As a powerful technology platform, it would not be surprising if protein microarrays will become one of the leading technologies in proteomic and diagnostic fields in the next decade.

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Acetylation of Yeast AMPK Controls Intrinsic Aging Independently of Caloric Restriction

Cited by 137 publications

References 69 publications

Bypassing the Requirement for an Essential MYST Acetyltransferase

Bypassing the Requirement for an Essential MYST Acetyltransferase

The SNF1 Kinase Ubiquitin-associated Domain Restrains Its Activation, Activity, and the Yeast Life Span

Overview of Protein Microarrays

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