Abstract
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.
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18 August 2020
A Correction to this paper has been published: https://doi.org/10.1038/s41418-020-00611-z
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Acknowledgements
We would like to thank Dr. Derrick Rancourt and Dr. Tannin Schmidt for use of the Olympus IX70 and the Olympus Fluoview FV1000 fluorescence microscopes, respectively. This work was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canadian Cancer Society (CCS), the Breast Cancer Society of Canada (BCSC) and the Calgary Centre for Cancer Research (CCCR) to S. Bonni, and the National Institutes of Health (NIH) - NS041021 to A. Bonni. A. Chanda is a recipient of a Charbonneau Cancer Institute Director’s Award for Excellence in Research Productivity, an Eyes High International Doctoral Scholarship, a William H Davies Medical Research Scholarship, an Achievers in Medical Science (AIMS) Graduate Recruitment Scholarship, and an Eyes High Recruitment Award from the University of Calgary. K. Karve and A. Sarkar are recipients of a Doctoral Scholarship and an Eyes High Doctoral Recruitment Scholarship, respectively, from the University of Calgary.
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ASC is currently employed at Fog Pharma, USA. However, this study is neither funded nor associated in any manner with Fog Pharma. The other authors declare no conflict of interest.
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Chanda, A., Ikeuchi, Y., Karve, K. et al. PIAS1 and TIF1γ collaborate to promote SnoN SUMOylation and suppression of epithelial–mesenchymal transition. Cell Death Differ 28, 267–282 (2021). https://doi.org/10.1038/s41418-020-0599-8
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DOI: https://doi.org/10.1038/s41418-020-0599-8
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