PIAS1 and TIF1γ collaborate to promote SnoN SUMOylation and suppression of epithelial-mesenchymal transition

SUMO E3 ligases specify protein substrates for SUMOylation. The SUMO E3 ligases PIAS1 and TIF1 gamma target the transcriptional regulator SnoN for SUMOylation leading to suppression of epithelial-mesenchymal transition (EMT). Whether and how TIF1 gamma and PIAS1 might coordinate SnoN SUMOylation and regulation of EMT remained unknown. Here, we reveal that SnoN associates simultaneously with both TIF1 gamma and PIAS1, leading to a trimeric protein complex. Hence, PIAS1 and TIF1 gamma collaborate to promote the SUMOylation of SnoN. Importantly, loss of function studies of PIAS1 and TIF1 gamma 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.

Automated summary

Studies show that SUMO E3 ligases PIAS1 and TIF1γ collaborate to promote the SUMOylation of SnoN, suppressing EMT in breast cell-derived tissue organoids. These E3 ligases act in an interdependent manner in the regulation process.