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Deubiquitinases as a signaling target of oxidative stress
Author(s) -
Huang Tony T
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.782.6
Subject(s) - deubiquitinating enzyme , proteases , dna damage , ubiquitin , oxidative stress , microbiology and biotechnology , cysteine , cysteine protease , reactive oxygen species , signal transduction , regulator , intracellular , biochemistry , biology , chemistry , enzyme , dna , gene
Deubiquitinating enzymes (DUBs) constitute a large family of cysteine proteases that have broad impact on numerous biological and pathological processes, including the regulation of genomic stability. DUBs are often assembled onto multiprotein complexes to assist in their localization and substrate selection, yet it remains unclear how the enzymatic activity of DUBs is modulated by intracellular signals. Herein, we show that bursts of reactive oxygen species (ROS) reversibly inactivate DUBs through the oxidation of the catalytic cysteine residue. Importantly, USP1, a key regulator of genomic stability, is reversibly inactivated upon oxidative stress. This, in part, explains the rapid nature of PCNA monoubiquitination‐dependent DNA damage tolerance in response to oxidative DNA damage in replicating cells. We propose that DUBs of the cysteine protease family act as ROS sensors in human cells and that ROS‐mediated DUB inactivation is a critical mechanism for fine‐tuning stress‐activated signaling pathways.