title: S-nitrosylation of XIAP at Cys 213 of BIR2 domain impairs XIAP's anti-caspase 3 activity and anti-apoptotic function.
abstract: X-linked inhibitor of apoptosis (XIAP) is a protein that possesses anti-apoptotic function and dysregulation of it has been linked to a number human disease such as cancers and neurodegenerative disorders. In our previous study, we have found that nitric oxide (NO) can modulate the anti-apoptotic function of XIAP and found that this can contribute to the pathogenesis of Parkinson's disease. Specifically, we found that modification of baculoviral IAP repeat 2 of XIAP by S-nitrosylation can compromise XIAP's anti-caspase 3 and anti-apoptotic function. In this study, we report that cysteine (Cys) 90, Cys 213 and Cys 327 can be specifically S-nitrosylated by NO. We found that mutations of Cys 90 and Cys 327 affect the normal structure of XIAP. More importantly, we found that S-nitrosylation of XIAP Cys 213 impairs the anti-caspase 3 and anti-apoptotic function of XIAP that we observed in our previous study.
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wu
authors.forename: Oi Wan
authors.initials: OW
authors.lastname: Wan
authors.forename: Kenny K K
authors.initials: KK
authors.lastname: Chung
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D002460:Cell Line; D003545:Cysteine / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D051636:X-Linked Inhibitor of Apoptosis Protein; D009569:Nitric Oxide; D053148:Caspase 3; D003545:Cysteine