Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey

Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Molecular Cell (Impact Factor: 14.02). 09/2006; 23(4):607-18. DOI: 10.1016/j.molcel.2006.06.026
Source: PubMed


Acetylation of proteins on lysine residues is a dynamic posttranslational modification that is known to play a key role in regulating transcription and other DNA-dependent nuclear processes. However, the extent of this modification in diverse cellular proteins remains largely unknown, presenting a major bottleneck for lysine-acetylation biology. Here we report the first proteomic survey of this modification, identifying 388 acetylation sites in 195 proteins among proteins derived from HeLa cells and mouse liver mitochondria. In addition to regulators of chromatin-based cellular processes, nonnuclear localized proteins with diverse functions were identified. Most strikingly, acetyllysine was found in more than 20% of mitochondrial proteins, including many longevity regulators and metabolism enzymes. Our study reveals previously unappreciated roles for lysine acetylation in the regulation of diverse cellular pathways outside of the nucleus. The combined data sets offer a rich source for further characterization of the contribution of this modification to cellular physiology and human diseases.

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    • "Types of PTMs include reversible acetylation , phosphorylation, SUMOylation, glycosylation, and ubiquitination (Meek and Anderson, 2009; Zhao et al., 2011). Recently, acetylation and deacetylation of histones and nonhistone proteins have been shown to be involved in the control of cellular energy metabolism (Kim et al., 2006; Guan and Xiong, 2011). Protein acetylation on lysine residues is regulated by two types of enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). "
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    ABSTRACT: Post-translational modifications (PTMs) of transcription factors play a crucial role in regulating metabolic homeostasis. These modifications include phosphorylation, methylation, acetylation, ubiquitination, SUMOylation, and O-GlcNAcylation. Recent studies have shed light on the importance of lysine acetylation at nonhistone proteins including transcription factors. Acetylation of transcription factors affects subcellular distribution, DNA affinity, stability, transcriptional activity, and current investigations are aiming to further expand our understanding of the role of lysine acetylation of transcription factors. In this review, we summarize recent studies that provide new insights into the role of protein lysine-acetylation in the transcriptional regulation of metabolic homeostasis.
    Protein & Cell 09/2015; 6(11). DOI:10.1007/s13238-015-0204-y · 3.25 Impact Factor
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    • "Further analysis of the data revealed that total stretch of atp6 was 598 bp, which comprised of start codon and abbreviated stop codon (T). Presence of abbreviated stop codon in atp6 gene may be attributed as a consistent feature with annotation in the mt genomes of other ascaridoid nematodes (Okimoto et al. 1992, Lavrov and Brown 2001, Kim et al. 2006, Li et al. 2008 "

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    • "How various mitochondrial functions are coordinated to meet cellular requirements represents a central question in mitochondrial biology. A potential role for lysine acetylation in this process was suggested by proteomic studies showing that a large fraction of mitochondrial proteins are acetylated (Kim et al, 2006; Choudhary et al, 2009; Zhao et al, 2010). The SIRT3 protein, a member of the sirtuin deacylase family, was initially shown to deacetylate and thereby activate a mitochondrial enzyme involved in acetyl-CoA synthesis (see Kumar & Lombard, 2015 and references therein). "
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    ABSTRACT: Lysine acetylation on numerous mitochondrial proteins, targeted by the sirtuin deacylase SIRT3, has been proposed to play a major role in regulating diverse mitochondrial functions, particularly in the liver. A new study by Weinert, Choudhary, and colleagues, in this issue of The EMBO Journal, finds that the absolute levels of hepatic mitochondrial protein acetylation in wild-type mice are extremely low and may be insufficient to exert regulatory effects.
    The EMBO Journal 09/2015; 34(21). DOI:10.15252/embj.201592927 · 10.43 Impact Factor
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