Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, Canada.
Molecular Biology Program, Université de Montréal, Montréal, Canada.
Nat Commun. 2020 Feb 11;11(1):834. 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.
STAT1 激活蛋白抑制剂（PIAS1）是一种 E3 SUMO 连接酶，在各种细胞途径中发挥重要作用。越来越多的证据表明，PIAS1 在包括前列腺癌和肺癌在内的各种人类恶性肿瘤中过表达。在这里，我们使用定量 SUMO 蛋白质组学以系统的方式鉴定 PIAS1 的潜在底物。我们在 544 种蛋白质上鉴定了 983 个 SUMO 位点，其中 62 种蛋白质被指定为潜在的 PIAS1 底物。特别是，波形蛋白（VIM），一种参与细胞骨架组织和细胞运动的 III 型中间丝蛋白，在 Lys-439 和 Lys-445 残基处被 PIAS1 SUMO 化。VIM SUMO 化对于其动态解聚是必需的，并且表达不可 SUMO 化 VIM 突变体的细胞表现出迁移水平降低。我们的方法不仅能够鉴定 E3 SUMO 连接酶底物，还为 PIAS1 和 VIM SUMO 化对细胞运动的意想不到的作用提供了有价值的生物学见解。
