title: S-nitrosylation of IRP2 regulates its stability via the ubiquitin-proteasome pathway.
abstract: Nitric oxide (NO) is an important signaling molecule that interacts with different targets depending on its redox state. NO can interact with thiol groups resulting in S-nitrosylation of proteins, but the functional implications of this modification are not yet fully understood. We have reported that treatment of RAW 264.7 cells with NO caused a decrease in levels of iron regulatory protein 2 (IRP2), which binds to iron-responsive elements present in untranslated regions of mRNAs for several proteins involved in iron metabolism. In this study, we show that NO causes S-nitrosylation of IRP2, both in vitro and in vivo, and this modification leads to IRP2 ubiquitination followed by its degradation in the proteasome. Moreover, mutation of one cysteine (C178S) prevents NO-mediated degradation of IRP2. Hence, S-nitrosylation is a novel signal for IRP2 degradation via the ubiquitin-proteasome pathway.
authors.affiliation: Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.
authors.forename: Sangwon
authors.initials: S
authors.lastname: Kim
authors.forename: Simon S
authors.initials: SS
authors.lastname: Wing
authors.forename: Prem
authors.initials: P
authors.lastname: Ponka
mesh_terms: D000818:Animals; D019556:COS Cells; D003545:Cysteine / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D035942:Iron Regulatory Protein 2 / Q000378:metabolism*; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D009599:Nitroprusside / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D009097:Multienzyme Complexes; D025801:Ubiquitin; D009599:Nitroprusside; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D035942:Iron Regulatory Protein 2; D003545:Cysteine