Quantitative SUMO proteomics identifies PIAS1 substrates involved in cell migration and motility

• Published in: Nature communications 2020-02, Vol.11 (1), p.834-834, Article 834
• Main Authors: Li, Chongyang, McManus, Francis P., Plutoni, Cédric, Pascariu, Cristina Mirela, Nelson, Trent, Alberici Delsin, Lara Elis, Emery, Gregory, Thibault, Pierre
• Format: Article
• Language: English
• Subjects: 14/19; 38/1; 42/109; 42/70; 49/31; 631/337/458/538; 631/45/475; 631/45/612/1228; 631/80/128/1580; 82/51; 82/58; 82/80; 82/81; Cell adhesion & migration; Cell migration; Cell Movement - physiology; Cell Proliferation; Cytoskeletal Proteins - metabolism; Cytoskeleton; Gene Knockout Techniques; HEK293 Cells; HeLa Cells; Humanities and Social Sciences; Humans; Motility; multidisciplinary; Mutants; Prostate; Protein Inhibitors of Activated STAT - genetics; Protein Inhibitors of Activated STAT - metabolism; Protein Interaction Maps; Proteins; Proteomics; Science; Science (multidisciplinary); Sequence Analysis, Protein; Small Ubiquitin-Related Modifier Proteins - genetics; Small Ubiquitin-Related Modifier Proteins - metabolism; Stat1 protein; Substrates; SUMO protein; SUMO-1 Protein - genetics; SUMO-1 Protein - metabolism; Sumoylation; Ubiquitin-Protein Ligases - metabolism; Vimentin; Vimentin - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-14581-w

The protein inhibitor of activated STAT1 (PIAS1) is an E3 SUMO ligase that plays important roles in various cellular pathways. Increasing evidence shows that PIAS1 is overexpressed in various human malignancies, including prostate and lung cancers. Here we used quantitative SUMO proteomics to identify potential substrates of PIAS1 in a system-wide manner. We identified 983 SUMO sites on 544 proteins, of which 62 proteins were assigned as putative PIAS1 substrates. In particular, vimentin (VIM), a type III intermediate filament protein involved in cytoskeleton organization and cell motility, was SUMOylated by PIAS1 at Lys-439 and Lys-445 residues. VIM SUMOylation was necessary for its dynamic disassembly and cells expressing a non-SUMOylatable VIM mutant showed a reduced level of migration. Our approach not only enables the identification of E3 SUMO ligase substrates but also yields valuable biological insights into the unsuspected role of PIAS1 and VIM SUMOylation on cell motility. PIAS1 is an E3 SUMO ligase involved in various cellular processes. Here, the authors use quantitative proteomics to identify potential PIAS1 substrates in human cells and elucidate the biological consequences of PIAS1-mediated SUMOylation of vimentin.