title: Ataxin-3 protects cells against H2O2-induced oxidative stress by enhancing the interaction between Bcl-X(L) and Bax.
abstract: Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder associated with polyglutamine (polyQ) protein ataxin-3. Ataxin-3 is a multi-functional protein, but the precise mechanisms underlying the cellular functions of ataxin-3 remain to be elucidated. Here we demonstrate that ataxin-3 plays a protective role against cellular oxidative stress induced by H2O2 in a Bcl-XL-dependent manner. Ataxin-3 directly interacts with Bcl-XL. The N-terminus of ataxin-3 and the C-terminus of Bcl-XL are essential for the interaction. Ataxin-3 promotes the interaction between Bcl-XL and Bax, but does not affect the ubiquitination and degradation of Bcl-XL. Our data suggest that ataxin-3 plays an important role in regulating the Bcl-XL-Bax-mediated anti-oxidative response by modulating the interaction between Bcl-XL and Bax.
authors.affiliation: Laboratory of Molecular Neuropathology, Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science & Technology of China, Chinese Academy of Sciences, Hefei, Anhui 230027, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhou
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Ren
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: Z
authors.initials: Z
authors.lastname: Ying
authors.forename: G
authors.initials: G
authors.lastname: Wang
mesh_terms: D000067699:Ataxin-3; D002460:Cell Line; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D015151:Immunoblotting; D047468:Immunoprecipitation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000502:physiology*; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: C494826:BAX protein, human; C494811:BCL2L1 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016877:Oxidants; D012097:Repressor Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D006861:Hydrogen Peroxide; C092341:ATXN3 protein, human; D000067699:Ataxin-3