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Revealing dynamic protein acetylation across subcellular compartments

ABSTRACT: Protein acetylation is a widespread post-translational modification implicated in many cellular processes. Recent advances in mass spectrometry have enabled the cataloging of thousands of sites throughout the cell, however identifying regulatory acetylation marks has proven to be a daunting task. Knowledge of the kinetics and stoichiometry of site-specific acetylation are important factors to uncover function. Here, an improved method of quantifying acetylation stoichiometry was developed and validated, providing a detailed landscape of dynamic acetylation stoichiometry within cellular compartments. The dynamic nature of site-specific acetylation in response to serum stimulation was revealed. In two distinct human cell lines, growth factor stimulation led to site-specific, temporal acetylation changes, revealing diverse kinetic profiles that clustered into several groups. Overlap of dynamic acetylation sites among the two cell types suggested similar regulatory control points across major cellular pathways that include splicing, translation, and protein homeostasis. Rapid increases in acetylation on protein translational machinery suggests a positive regulatory role under pro-growth conditions. Lastly, higher median stoichiometry was observed in cellular compartments where active acetyltransferases are well-described.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: John Denu

PROVIDER: MSV000084029 | MassIVE | Mon Jul 01 10:13:00 BST 2019

SECONDARY ACCESSION(S): PXD014453

REPOSITORIES: MassIVE

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