Department of Biochemistry and Molecular Biology, Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Cell Death Differ. 2021 Jan;28(1):267-282. doi: 10.1038/s41418-020-0599-8. Epub 2020 Aug 7.
SUMO E3 ligases specify protein substrates for SUMOylation. The SUMO E3 ligases PIAS1 and TIF1γ target the transcriptional regulator SnoN for SUMOylation leading to suppression of epithelial-mesenchymal transition (EMT). Whether and how TIF1γ and PIAS1 might coordinate SnoN SUMOylation and regulation of EMT remained unknown. Here, we reveal that SnoN associates simultaneously with both TIF1γ and PIAS1, leading to a trimeric protein complex. Hence, PIAS1 and TIF1γ collaborate to promote the SUMOylation of SnoN. Importantly, loss of function studies of PIAS1 and TIF1γ suggest that these E3 ligases act in an interdependent manner to suppress EMT of breast cell-derived tissue organoids. Collectively, our findings unveil a novel mechanism by which SUMO E3 ligases coordinate substrate SUMOylation with biological implications.
SUMO E3 连接酶将蛋白质底物特定位点用于 SUMO 化。SUMO E3 连接酶 PIAS1 和 TIF1γ 靶向转录调节剂 SnoN 进行 SUMO 化，从而抑制上皮-间充质转化 (EMT)。然而，TIF1γ 和 PIAS1 是否以及如何协调 SnoN SUMO 化和 EMT 的调节尚不清楚。在这里，我们揭示了 SnoN 同时与 TIF1γ 和 PIAS1 结合，形成三聚体蛋白复合物。因此，PIAS1 和 TIF1γ 协作促进 SnoN 的 SUMO 化。重要的是，PIAS1 和 TIF1γ 的功能丧失研究表明，这些 E3 连接酶以相互依赖的方式发挥作用，抑制乳腺细胞衍生组织类器官的 EMT。总之，我们的研究结果揭示了 SUMO E3 连接酶与生物学意义相关的底物 SUMO 化协调的新机制。
