Daniel Liebler
Faculty Member
Last active: 2/15/2016

Site-specific mapping and quantification of protein S-sulphenylation in cells.

Yang J, Gupta V, Carroll KS, Liebler DC
Nat Commun. 2014 5: 4776

PMID: 25175731 · PMCID: PMC4167403 · DOI:10.1038/ncomms5776

Cysteine S-sulphenylation provides redox regulation of protein functions, but the global cellular impact of this transient post-translational modification remains unexplored. We describe a chemoproteomic workflow to map and quantify over 1,000 S-sulphenylation sites on more than 700 proteins in intact cells. Quantitative analysis of human cells stimulated with hydrogen peroxide or epidermal growth factor measured hundreds of site selective redox changes. Different cysteines in the same proteins displayed dramatic differences in susceptibility to S-sulphenylation. Newly discovered S-sulphenylations provided mechanistic support for proposed cysteine redox reactions and suggested novel redox mechanisms, including S-sulphenyl-mediated redox regulation of the transcription factor HIF1A by SIRT6. S-sulphenylation is favored at solvent-exposed protein surfaces and is associated with sequence motifs that are distinct from those for other thiol modifications. S-sulphenylations affect regulators of phosphorylation, acetylation and ubiquitylation, which suggest regulatory crosstalk between redox control and signalling pathways.

MeSH Terms (17)

Acetylation Cell Line, Tumor Cysteine Epidermal Growth Factor Epithelial Cells Gene Expression Humans Hydrogen Peroxide Hypoxia-Inducible Factor 1, alpha Subunit Molecular Sequence Annotation Oxidation-Reduction Peptide Mapping Phosphorylation Protein Processing, Post-Translational Sirtuins Sulfenic Acids Ubiquitination

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