The ubiquitin-like modifier FAT10 interferes with SUMO activation

The covalent attachment of the cytokine-inducible ubiquitin-like modifier HLA-F adjacent transcript 10 (FAT10) to hundreds of substrate proteins leads to their rapid degradation by the 26 S proteasome independently of ubiquitylation. Here, we identify another function of FAT10, showing that it interferes with the activation of SUMO1/2/3 in vitro and down-regulates SUMO conjugation and the SUMO-dependent formation of promyelocytic leukemia protein (PML) bodies in cells. Mechanistically, we show that FAT10 directly binds to and impedes the activity of the heterodimeric SUMO E1 activating enzyme AOS1/UBA2 by competing very efficiently with SUMO for activation and thioester formation. Nevertheless, activation of FAT10 by AOS1/UBA2 does not lead to covalent conjugation of FAT10 with substrate proteins which relies on its cognate E1 enzyme UBA6. Hence, we report that one ubiquitin-like modifier (FAT10) inhibits the conjugation and function of another ubiquitin-like modifier (SUMO) by impairing its activation.

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570 Biowissenschaften, Biologie

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AICHEM, Annette, Carolin SAILER, Stella RYU, Nicola CATONE, Nicolas STANKOVIC-VALENTIN, Gunter SCHMIDTKE, Frauke MELCHIOR, Florian STENGEL, Marcus GRÖTTRUP, 2019. The ubiquitin-like modifier FAT10 interferes with SUMO activation. In: Nature communications. 2019, 10, 4452. eISSN 2041-1723. Available under: doi: 10.1038/s41467-019-12430-z

BibTex

@article{Aichem2019-10-01ubiqu-47200,
  year={2019},
  doi={10.1038/s41467-019-12430-z},
  title={The ubiquitin-like modifier FAT10 interferes with SUMO activation},
  volume={10},
  journal={Nature communications},
  author={Aichem, Annette and Sailer, Carolin and Ryu, Stella and Catone, Nicola and Stankovic-Valentin, Nicolas and Schmidtke, Gunter and Melchior, Frauke and Stengel, Florian and Gröttrup, Marcus},
  note={Article Number: 4452}
}

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