Mining the Thiol Proteome for Sulfenic Acid Modifications Reveals New Targets for Oxidation in Cells
Citations Over TimeTop 1% of 2009 papers
Abstract
Oxidation of cysteine to sulfenic acid has emerged as a biologically relevant post-translational modification with particular importance in redox-mediated signal transduction; however, the identity of modified proteins remains largely unknown. We recently reported DAz-1, a cell-permeable chemical probe capable of detecting sulfenic acid modified proteins directly in living cells. Here we describe DAz-2, an analogue of DAz-1 that exhibits significantly improved potency in vitro and in cells. Application of this new probe for global analysis of the sulfenome in a tumor cell line identifies most known sulfenic acid modified proteins: 14 in total, plus more than 175 new candidates, with further testing confirming oxidation in several candidates. The newly identified proteins have roles in signal transduction, DNA repair, metabolism, protein synthesis, redox homeostasis, nuclear transport, vesicle trafficking, and ER quality control. Cross-comparison of these results with those from disulfide, S-glutathionylation, and S-nitrosylation proteomes reveals moderate overlap, suggesting fundamental differences in the chemical and biological basis for target specificity. The combination of selective chemical enrichment and live-cell compatibility makes DAz-2 a powerful new tool with the potential to reveal new regulatory mechanisms in signaling pathways and identify new therapeutic targets.
Related Papers
- → Regulation of PTP1B via Glutathionylation of the Active Site Cysteine 215(1999)489 cited
- → A critical evaluation of probes for cysteine sulfenic acid(2020)25 cited
- → Shining light on cysteine modification: connecting protein conformational dynamics to catalysis and regulation(2019)24 cited
- → A simple isotopic labeling method to study cysteine oxidation in Alzheimer’s disease: oxidized cysteine-selective dimethylation (OxcysDML)(2016)17 cited
- → Proteome-Wide Survey Reveals Norbornene Is Complementary to Dimedone and Related Nucleophilic Probes for Cysteine Sulfenic Acid(2019)