AI Article Synopsis

  • Ubiquitin and ubiquitin-like conjugation involves specific E1, E2, and E3 enzymes, with E3 enzymes determining which substrates are targeted.
  • Through mass spectrometry, over 6,500 SUMO2/3 target proteins have been identified, allowing for an in-depth study of SUMO E3 substrate interactions.
  • The research using SUMO-activated target traps (SATTs) identified 427 SUMO1 and 961 SUMO2/3 targets specific to various E3 enzymes, leading to the creation of an interactive web tool for exploring these E3-to-target relationships.

Article Abstract

Ubiquitin and ubiquitin-like conjugation cascades consist of dedicated E1, E2, and E3 enzymes with E3s providing substrate specificity. Mass spectrometry-based approaches have enabled the identification of more than 6500 SUMO2/3 target proteins. The limited number of SUMO E3s provides the unique opportunity to systematically study E3 substrate wiring. We developed SUMO-activated target traps (SATTs) and systematically identified substrates for eight different SUMO E3s, PIAS1, PIAS2, PIAS3, PIAS4, NSMCE2, ZNF451, LAZSUL (ZNF451-3), and ZMIZ2. SATTs enabled us to identify 427 SUMO1 and 961 SUMO2/3 targets in an E3-specific manner. We found pronounced E3 substrate preference. Quantitative proteomics enabled us to measure substrate specificity of E3s, quantified using the SATT index. Furthermore, we developed the Polar SATTs web-based tool to browse the dataset in an interactive manner. Overall, we uncover E3-to-target wiring of 1388 SUMO substrates, highlighting unique and overlapping sets of substrates for eight different SUMO E3 ligases.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10396300PMC
http://dx.doi.org/10.1126/sciadv.adh2073DOI Listing

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Article Synopsis
  • Ubiquitin and ubiquitin-like conjugation involves specific E1, E2, and E3 enzymes, with E3 enzymes determining which substrates are targeted.
  • Through mass spectrometry, over 6,500 SUMO2/3 target proteins have been identified, allowing for an in-depth study of SUMO E3 substrate interactions.
  • The research using SUMO-activated target traps (SATTs) identified 427 SUMO1 and 961 SUMO2/3 targets specific to various E3 enzymes, leading to the creation of an interactive web tool for exploring these E3-to-target relationships.
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