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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Culture Techniques, Three Dimensional
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Cell Line, Tumor
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Epithelial-Mesenchymal Transition / genetics*
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Gene Expression Regulation
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HEK293 Cells
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Humans
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Intracellular Signaling Peptides and Proteins / genetics*
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Intracellular Signaling Peptides and Proteins / metabolism
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Mice
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Protein Binding
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Protein Inhibitors of Activated STAT / genetics*
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Protein Inhibitors of Activated STAT / metabolism
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism
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Small Ubiquitin-Related Modifier Proteins / genetics*
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Small Ubiquitin-Related Modifier Proteins / metabolism
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Sumoylation / genetics*
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Ubiquitin-Protein Ligases / metabolism
Substances
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Intracellular Signaling Peptides and Proteins
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PIAS1 protein, human
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Protein Inhibitors of Activated STAT
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Proto-Oncogene Proteins
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SKIL protein, human
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Small Ubiquitin-Related Modifier Proteins
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TRIM33 protein, human
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Transcription Factors
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Ubiquitin-Protein Ligases