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Regulatory Mechanism of Soluble Epoxide Hydrolase by Post‐Translational Modifications
Author(s) -
Luria Ayala R,
Tsai HsingJu,
Lu Anthony,
Morisseau Christophe,
Hammock Bruce D
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/fasebj.22.1_supplement.479.37
Subject(s) - sumo protein , lysine , chemistry , epoxide hydrolase 2 , sumo enzymes , biochemistry , ubiquitin , active site , enzyme , residue (chemistry) , microbiology and biotechnology , biology , amino acid , gene
Sumoylation is an important post‐translational modification that provides a rapid and reversible means for controlling the activity, subcellular localization, and stability of target proteins. We have examined the covalent attachment of the small ubiqutin‐like modifier (SUMO) proteins to a consensus sequence ([psi]KXE) on the soluble epoxide hydrolase (EPHX2; sEH) enzyme. This enzyme has epoxide hydrolase activity on the C‐terminal domain and a phosphatase activity on the N‐terminus. Polymorphism in EPHX2 have been recently discovered (K55R) that is associated with risk of incident of coronary heart disease events. Interestingly, features of the sEH N‐terminal catalytic site showing a consensus site for SUMOylation (VKEP) with lysine residue at position 160. This and another human‐specific site of SUMOylation (MKGE with lysine residue at position 55), suggest a post‐translational modification and regulatory mechanism of sEH by SUMOylation. Our primary aim of this study was to determine whether sEH can be in vitro SUMOylated and defines its regulatory role of SUMOylation in its both C and N‐terminus activity. Indeed, SUMOylated process catalyzes the formation of polymeric chains of SUMO‐2 and SUMO‐3 on sEH in vitro, and was detected in vivo. We also identified the SUMOylated site on the sEH sequence and revealed its regulatory mechanism. Supported by NIEHS Grant R37 ES02710, NIEHS SBRP Grant P42 ES04699.