The BAG2 and BAG5 proteins inhibit the ubiquitination of pathogenic ataxin3-80Q

Int J Neurosci. 2015 May;125(5):390-4. doi: 10.3109/00207454.2014.940585. Epub 2014 Aug 19.

Abstract

The expansion of a polyglutamine domain in the protein ataxin3 causes spinocerebellar ataxia type-3 (SCA3). However, there is little information to date about the upstream proteins in the ubiquitin-proteasome system of pathogenic ataxin3-80Q. Here, we report that BAG2 (Bcl-2 associated athanogene family protein 2) and BAG5 (Bcl-2-associated athanogene family protein 5) stabilise pathogenic ataxin3-80Q by inhibiting its ubiquitination as determined based on western blotting and co-immunofluorescence experiments. The association of the BAG2 and BAG5 proteins with pathogenic ataxin3-80Q strengthens the important roles of the BAG family in neurodegenerative diseases.

Keywords: BAG2; BAG5; pathogenic ataxin3-80Q; spinocerebellar ataxia type-3; ubiquitin-proteasome system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Analysis of Variance
  • Ataxin-3 / genetics
  • Ataxin-3 / metabolism*
  • Gene Expression Regulation / genetics
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Immunoprecipitation
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Peptides / genetics
  • Peptides / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transfection
  • Ubiquitination / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • BAG2 protein, human
  • BAG5 protein, human
  • Molecular Chaperones
  • Peptides
  • Repressor Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • polyglutamine
  • ATXN3 protein, human
  • Ataxin-3