Global, site-resolved analysis of ubiquitylation occupancy and turnover rate reveals systems properties

Gabriela Prus, Shankha Satpathy, Brian T. Weinert, Takeo Narita, Chunaram Choudhary*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

2 Citations (Scopus)
5 Downloads (Pure)

Abstract

Ubiquitylation regulates most proteins and biological processes in a eukaryotic cell. However, the site-specific occupancy (stoichiometry) and turnover rate of ubiquitylation have not been quantified. Here we present an integrated picture of the global ubiquitylation site occupancy and half-life. Ubiquitylation site occupancy spans over four orders of magnitude, but the median ubiquitylation site occupancy is three orders of magnitude lower than that of phosphorylation. The occupancy, turnover rate, and regulation of sites by proteasome inhibitors are strongly interrelated, and these attributes distinguish sites involved in proteasomal degradation and cellular signaling. Sites in structured protein regions exhibit longer half-lives and stronger upregulation by proteasome inhibitors than sites in unstructured regions. Importantly, we discovered a surveillance mechanism that rapidly and site-indiscriminately deubiquitylates all ubiquitin-specific E1 and E2 enzymes, protecting them against accumulation of bystander ubiquitylation. The work provides a systems-scale, quantitative view of ubiquitylation properties and reveals general principles of ubiquitylation-dependent governance.

Original languageEnglish
JournalCell
Volume187
Issue number11
Pages (from-to)2875-2892.e21
ISSN0092-8674
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Keywords

  • cell signaling
  • dynamics
  • mass spectrometry
  • occupancy
  • posttranslational modification
  • proteomics
  • turnover rate
  • ubiquitin signaling
  • ubiquitylation

Cite this