The Logic of the 26S Proteasome

Cell. 2017 May 18;169(5):792-806. doi: 10.1016/j.cell.2017.04.023.

Abstract

The ubiquitin proteasome pathway is responsible for most of the protein degradation in mammalian cells. Rates of degradation by this pathway have generally been assumed to be determined by rates of ubiquitylation. However, recent studies indicate that proteasome function is also tightly regulated and determines whether a ubiquitylated protein is destroyed or deubiquitylated and survives longer. This article reviews recent advances in our understanding of the proteasome's multistep ATP-dependent mechanism, its biochemical and structural features that ensure efficient proteolysis and ubiquitin recycling while preventing nonselective proteolysis, and the regulation of proteasome activity by interacting proteins and subunit modifications, especially phosphorylation.

Keywords: proteasome phosphorylation; protein degradation; protein turnover; ubiquitin proteasome system.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Allosteric Regulation
  • Animals
  • Eukaryota / chemistry
  • Eukaryota / metabolism
  • Humans
  • Phosphorylation
  • Proteasome Endopeptidase Complex / chemistry*
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteolysis
  • Ubiquitination

Substances

  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease
  • Adenosine Triphosphatases