SUMO Proteomics Analyses Identify Protein Inhibitor of Activated STAT-Mediated Regulatory Networks Involved in Cell Cycle and Cell Proliferation.

Autor:	Li C; Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec H3T 1J4, Canada., Boutet A; Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec H3T 1J4, Canada.; Molecular Biology program, Université de Montréal, Montréal, Québec H3C 3J7, Canada., Pascariu CM; Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec H3T 1J4, Canada., Nelson T; Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec H3T 1J4, Canada.; Molecular Biology program, Université de Montréal, Montréal, Québec H3C 3J7, Canada., Courcelles M; Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec H3T 1J4, Canada., Wu Z; Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec H3T 1J4, Canada.; Department of Chemistry, Université de Montréal, Montréal, Québec H3C 3J7, Canada., Comtois-Marotte S; Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec H3T 1J4, Canada., Emery G; Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec H3T 1J4, Canada.; Department of Pathology and Cell Biology, Université de Montréal, Montréal, Québec H3C 3J7, Canada., Thibault P; Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec H3T 1J4, Canada.; Molecular Biology program, Université de Montréal, Montréal, Québec H3C 3J7, Canada.; Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Québec H3C 3J7, Canada.
Jazyk:	angličtina
Zdroj:	Journal of proteome research [J Proteome Res] 2023 Mar 03; Vol. 22 (3), pp. 812-825. Date of Electronic Publication: 2023 Feb 01.
DOI:	10.1021/acs.jproteome.2c00557
Abstrakt:	Protein inhibitor of activated STAT (PIAS) proteins are E3 SUMO ligases playing important roles in protein stability and signaling transduction pathways. PIAS proteins are overexpressed in the triple-negative breast cancer cell line MDA-MB-231, and PIAS knockout (KO) results in a reduction in cell proliferation and cell arrest in the S phase. However, the molecular mechanisms underlying PIAS functions in cell proliferation and cell cycle remain largely unknown. Here, we used quantitative SUMO proteomics to explore the regulatory role of PIAS SUMO E3 ligases upon CRISPR/Cas9 KO of individual PIAS. A total of 1422 sites were identified, and around 10% of SUMO sites were regulated following KO of one or more PIAS genes. We identified protein substrates that were either specific to individual PIAS ligase or regulated by several PIAS ligases. Ki-67 and TOP2A, which are involved in cell proliferation and epithelial-to-mesenchymal transition, are SUMOylated at several lysine residues by all PIAS ligases, suggesting a level of redundancy between these proteins. Confocal microscopy and biochemical experiments revealed that SUMOylation regulated TOP2A protein stability, while this modification is involved in the recruitment of Ki-67 nucleolar proteins containing the SUMO interacting motif. These results provide novel insights into both the redundant and specific regulatory mechanisms of cell proliferation and cell cycle mediated by PIAS SUMO E3 ligases.
Databáze:	MEDLINE
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