Article

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: 14.46). 09/2006; 23(4):607-18. DOI: 10.1016/j.molcel.2006.06.026
Source: PubMed

ABSTRACT 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.

0 Followers
  • Source
    • "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 "
  • Source
    • "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 "
    [Show abstract] [Hide abstract]
    ABSTRACT: This communication deals with molecular signature of Toxocara canis, T. cati and T. vitulorum collected from different geographical locations and host assemblages of India. T. vitulorum was collected from cattle, yak and mithun of West Bengal, Arunachal Pradesh and Nagaland, respectively. Isolated parasites were initially identified morphologically before proceeding for molecular characterization. ATP synthase subunit 6 (atp6) gene had a 598 bp stretch which contained both the punctuation codons but was unique in its characteristics due to presence of abbreviated stop codon (T). On the basis of phylogenetic analysis of atp6, 12S and transcribed spacer sequences, three species could be clustered in three different groups. Number of preferred and non preferred codons also varied in between three species of Toxocara of Indian origin. Atp6 gene had abundance in guanine (G) and thymine (T) bases which has also been described as unique characteristic for Neodermata. Restriction profile of transcribed sequences, 5.8S gene and a small fragment of 28S gene could differentiate Indian isolates of Toxocara in two different clades.
    The Indian journal of animal sciences 07/2015; 85(7):709–713. · 0.13 Impact Factor
  • Source
    • "However, very little is known about the formation of the GOT-MDH complex in response to metabolic changes and about the physiological significance of such a regulation. We and others have previously discovered that lysine acetylation is an evolutionarily conserved post-translational modification in the regulation of a wide range of cellular processes, particularly in nuclear transcription and cytoplasmic metabolism (Kim et al, 2006; Choudhary et al, 2009; Zhao et al, 2010). To date, more than 4,500 acetylated proteins have been identified (Lundby et al, 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The malate-aspartate shuttle is indispensable for the net transfer of cytosolic NADH into mitochondria to maintain a high rate of glycolysis and to support rapid tumor cell growth. The malate-aspartate shuttle is operated by two pairs of enzymes that localize to the mitochondria and cytoplasm, glutamate oxaloacetate transaminases (GOT), and malate dehydrogenases (MDH). Here, we show that mitochondrial GOT2 is acetylated and that deacetylation depends on mitochondrial SIRT3. We have identified that acetylation occurs at three lysine residues, K159, K185, and K404 (3K), and enhances the association between GOT2 and MDH2. The GOT2 acetylation at these three residues promotes the net transfer of cytosolic NADH into mitochondria and changes the mitochondrial NADH/NAD(+) redox state to support ATP production. Additionally, GOT2 3K acetylation stimulates NADPH production to suppress ROS and to protect cells from oxidative damage. Moreover, GOT2 3K acetylation promotes pancreatic cell proliferation and tumor growth in vivo. Finally, we show that GOT2 K159 acetylation is increased in human pancreatic tumors, which correlates with reduced SIRT3 expression. Our study uncovers a previously unknown mechanism by which GOT2 acetylation stimulates the malate-aspartate NADH shuttle activity and oxidative protection. © 2015 The Authors.
    The EMBO Journal 03/2015; 34(8). DOI:10.15252/embj.201591041 · 10.75 Impact Factor
Show more