KIAA0368-deficiency affects disassembly of 26S proteasome under oxidative stress condition

J Biochem. 2016 Jun;159(6):609-18. doi: 10.1093/jb/mvw006. Epub 2016 Jan 22.

Abstract

Many cellular stresses cause damages of intracellular proteins, which are eventually degraded by the ubiquitin and proteasome system. The proteasome is a multicatalytic protease complex composed of 20S core particle and the proteasome activators that regulate the proteasome activity. Extracellular mutants 29 (Ecm29) is a 200 kDa protein encoded by KIAA0368 gene, associates with the proteasome, but its role is largely unknown. Here, we generated KIAA0368-deficient mice and investigated the function of Ecm29 in stress response. KIAA0368-deficient mice showed normal peptidase activity and proteasome formation at normal condition. Under stressed condition, 26S proteasome dissociates in wild-type cells, but not in KIAA0368(-/-) cells. This response was correlated with efficient degradation of damaged proteins and resistance to oxidative stress of KIAA0368(-/-) cells. Thus, Ecm29 is involved in the dissociation process of 26S proteasome, providing clue to analyse the mechanism of proteasomal degradation under various stress condition.

Keywords: oxidative stress; proteasome; proteasome activators; protein degradation; ubiquitin.

MeSH terms

  • Animals
  • Mice
  • Mice, Knockout
  • Oxidative Stress / physiology*
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteolysis*

Substances

  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease