Modulating cellular balance of Rps3 mono-ubiquitination by both Hel2 E3 ligase and Ubp3 deubiquitinase regulates protein quality control

Exp Mol Med. 2017 Nov 17;49(11):e390. doi: 10.1038/emm.2017.128.

Abstract

When a ribosome complex is stalled during the translation elongation process in eukaryotes, the mono-ubiquitination of Rps3 has recently been shown to be critical to ribosome quality control. We have discovered that the regulatory role of Rps3 mono-ubiquitination is controlled by a deubiquitinase. We also showed that an autophagic signal appears to be coupled to the mono-ubiquitination of Rps3p through the entrance of Ubp3p into the autophagosome in yeasts. The mono-ubiquitination of the Rps3 protein is tightly modulated by reciprocal action between the Hel2p E3 ligase and the Ubp3p deubiquitinase in yeasts and the reciprocal action between the RNF123 E3 ligase and the USP10 deubiquitinase in mammalian cells. We also found that the Ubp3p/USP10 deubiquitinases critically modulate Hel2p/RNF123-mediated Rps3p mono-ubiquitination. In addition, we found that Hel2p/RNF123 and Ubp3p/USP10 appeared to be differently localized in the ribosome complex after ultraviolet irradiation. Together, our results support a model in which coordinated ubiquitination and deubiquitination activities can finely balance the level of regulatory Rps3p mono-ubiquitination in ribosome-associated quality control and autophagy processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Apoptosis
  • Cell Survival
  • Endopeptidases / metabolism*
  • Humans
  • Protein Biosynthesis
  • Protein Processing, Post-Translational
  • Ribosomal Proteins / metabolism*
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ubiquitin Thiolesterase / metabolism
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination

Substances

  • Amino Acids
  • RPS3 protein, S cerevisiae
  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • ribosomal protein S3
  • Hel2 protein, S cerevisiae
  • Ubiquitin-Protein Ligases
  • Endopeptidases
  • Ubiquitin Thiolesterase
  • UBP3 protein, S cerevisiae