The BAG2 protein stabilises PINK1 by decreasing its ubiquitination

Biochem Biophys Res Commun. 2013 Nov 15;441(2):488-92. doi: 10.1016/j.bbrc.2013.10.086.

Abstract

Mutations in the PTEN-induced putative kinase 1 (PINK1) gene cause an autosomal recessive form of Parkinson disease (PD). Thus far, little is known about what can regulate the ubiquitin proteasome pathway of PINK1. Here, we report BAG2 (Bcl-2-associated athanogene family protein 2), a member of the BAG family, which directly binds with and stabilises PINK1 by decreasing its ubiquitination. Moreover, we found that BAG2 also binds with the pathogenic R492X PINK1 mutation directly and more tightly. Moreover, BAG2 stabilises the R492X PINK1 mutation by decreasing its ubiquitination to a greater extent than the wild-type species. Our data correlate BAG2 to PINK1 for the first time, strengthening the important role of BAG2 in PD-related neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Stability
  • HEK293 Cells
  • Humans
  • Immunoprecipitation
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Mutation
  • Parkinson Disease / metabolism*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Ubiquitination*

Substances

  • BAG2 protein, human
  • Molecular Chaperones
  • Protein Kinases
  • PTEN-induced putative kinase