Ataxin-3 protects cells against H2O2-induced oxidative stress by enhancing the interaction between Bcl-X(L) and Bax

Neuroscience. 2013 Jul 23:243:14-21. doi: 10.1016/j.neuroscience.2013.03.047. Epub 2013 Apr 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxin-3
  • Cell Line
  • Humans
  • Hydrogen Peroxide / toxicity
  • Immunoblotting
  • Immunoprecipitation
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Oxidants / toxicity
  • Oxidative Stress / physiology*
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism*
  • Transfection
  • bcl-2-Associated X Protein / metabolism*
  • bcl-X Protein / metabolism*

Substances

  • BAX protein, human
  • BCL2L1 protein, human
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Oxidants
  • Repressor Proteins
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • Hydrogen Peroxide
  • ATXN3 protein, human
  • Ataxin-3