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SUMOylation of NADPH Oxidases Negatively Regulates Reactive Oxygen Species Production
Author(s) -
Pandey Deepesh,
Chen Feng,
Patel Anand,
Patel Vijay,
Rudic Daniel,
Wang CongYi,
Dimitropoulou Christiana,
Fulton David
Publication year - 2011
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.25.1_supplement.1093.4
Subject(s) - sumo protein , reactive oxygen species , sumo enzymes , nox1 , nadph oxidase , chemistry , oxidative stress , microbiology and biotechnology , enzyme , biochemistry , endogeny , nox4 , ubiquitin , biology , gene
Oxidative Stress derived from excess reactive oxygen species (ROS) is a potent stimulus regulating the attachment of Small Ubiquitin‐like MOdifiers (SUMO), a novel posttranslational modification of substrate proteins. Increased SUMOylation has been shown to provide protection from oxidative stress, but the mechanisms involved are unknown. Therefore, the goal of the current study was to determine whether SUMO influences the activity of the NADPH oxidases (Nox), a major source of ROS. We found that SUMO‐1 and the SUMO‐specific conjugating enzyme, UBC9 potently inhibit the activity of Nox5, whereas SUMO‐2 was ineffective. SUMO‐1 did not modify the expression of Nox5 and intracellular calcium levels but decreased Nox5 activity in an isolated enzyme activity assay suggesting a direct effect of SUMOylation on Nox enzymes. Indeed, we found that Nox5 was a substrate for SUMO in both in cells and in vitro SUMOylation reaction. SUMO‐1 also suppressed ROS generation from Nox1, 3 and 4. A SUMOylated form of Nox5 was detected in isolated human saphenous veins and inhibition of endogenous SUMOylation with siRNA to SUMO‐1 or UBC9 or with the inhibitor, anacardic acid potentiates ROS production from HEK cells, human smooth muscle cells and isolated neutrophils. Together, these results suggest that SUMO modification of Nox enzymes is an important regulatory mechanism that limits the production of ROS to diminish cellular stress.