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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/PMC10396300 | PMC |
| http://dx.doi.org/10.1126/sciadv.adh2073 | DOI Listing |
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SUMO-Activated Target Traps (SATTs) for the Identification of Specific SUMOylated Proteins for an E3 Ligase of Interest.
Methods Mol Biol
August 2025
Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Sevilla, Spain.
SUMOylation is a dynamic and reversible post-translational modification that occurs on acceptor lysines of substrate proteins. SUMO is conjugated via a dedicated enzymatic cascade of E1-E2-E3 enzymes, where the E3 confers substrate specificity. More than 6500 SUMO2/3 target proteins have been identified by mass spectrometry-based proteomics with important regulatory roles, predominantly in nuclear processes.
View Article and Find Full Text PDFSUMO-activated target traps (SATTs) enable the identification of a comprehensive E3-specific SUMO proteome.
Sci Adv
August 2023
Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands.
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.