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Mol Cell Proteomics. 2015 Jan;14(1):162-76. doi: 10.1074/mcp.M114.043141. Epub 2014 Nov 7.

Acetylome profiling reveals overlap in the regulation of diverse processes by sirtuins, gcn5, and esa1.

Author information

1
From the ‡Department of Biochemistry and Biophysics, University of California, San Francisco, 1450 3rd Street, San Francisco, CA, 94158; mdowne2@uottawa.ca.
2
§Cellular and Molecular Pharmacology, University of California, San Francisco, 1700 4th Street, QB3, San Francisco, CA, 94158;
3
¶Department of Physiology and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158.
4
From the ‡Department of Biochemistry and Biophysics, University of California, San Francisco, 1450 3rd Street, San Francisco, CA, 94158;

Abstract

Although histone acetylation and deacetylation machineries (HATs and HDACs) regulate important aspects of cell function by targeting histone tails, recent work highlights that non-histone protein acetylation is also pervasive in eukaryotes. Here, we use quantitative mass-spectrometry to define acetylations targeted by the sirtuin family, previously implicated in the regulation of non-histone protein acetylation. To identify HATs that promote acetylation of these sites, we also performed this analysis in gcn5 (SAGA) and esa1 (NuA4) mutants. We observed strong sequence specificity for the sirtuins and for each of these HATs. Although the Gcn5 and Esa1 consensus sequences are entirely distinct, the sirtuin consensus overlaps almost entirely with that of Gcn5, suggesting a strong coordination between these two regulatory enzymes. Furthermore, by examining global acetylation in an ada2 mutant, which dissociates Gcn5 from the SAGA complex, we found that a subset of Gcn5 targets did not depend on an intact SAGA complex for targeting. Our work provides a framework for understanding how HAT and HDAC enzymes collaborate to regulate critical cellular processes related to growth and division.

PMID:
25381059
PMCID:
PMC4288252
DOI:
10.1074/mcp.M114.043141
[Indexed for MEDLINE]
Free PMC Article

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