Premium
Molecular basis of the redox regulation of SUMO proteases: a protective mechanism of intermolecular disulfide linkage against irreversible sulfhydryl oxidation
Author(s) -
Xu Zheng,
Lam Levina Suk Mi,
Lam Lok Hei,
Chau So Fun,
Ng Tzi Bun,
Au Shan Wing Ngor
Publication year - 2008
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/fj.06-7871com
Subject(s) - sumo protein , chemistry , proteases , cysteine , sumo enzymes , biochemistry , sulfenic acid , disulfide linkage , enzyme , proteolysis , oxidative stress , cysteine protease , dithiothreitol , oxidative phosphorylation , ubiquitin , gene
Sumoylation has emerged as an indispensable post‐translational modification that modulates the functions of a broad spectrum of proteins. Recent studies have demonstrated that reactive oxygen species influence the equilibrium of sumoylation‐desumoylation. We show herein that H 2 O 2 induces formation of an intermolecular disulfide linkage of human SUMO protease SENP1 via the active‐site Cys 603 and a unique residue Cys 613. Such reversible modification confers a higher recovery of enzyme activity, which is also observed in yeast Ulp1, but not in human SENP2, suggesting its protective role against irreversible sulfhydryl oxidation. In vivo formation of a disulfide‐linked dimer of SENP1 is also detected in cultured cells in response to oxidative stress. The modifications are further elucidated by the crystal structures of Ulp1 with the catalytic cysteine oxidized to sulfenic, sulfinic, and sulfonic acids. Our findings suggest that, in addition to SUMO conjugating enzymes, SUMO proteases may act as redox sensors and effectors modulating the des‐umoylation pathway and specific cellular responses to oxidative stress.— Xu, Z., Lam, L. S. M., Lam, L. H., Chau, S. F., Ng, T. B., Au, S. W. N. Molecular basis of the redox regulation of SUMO proteases: a protective mechanism of intermolecular disulfide linkage against irreversible sulfhydryl oxidation. FASEB J. 22, 127–137 (2008)