The ubiquitin-like modifier FAT10 interferes with SUMO activation

• Verfasst von: Aichem, Annette [VerfasserIn]
• Verfasst von: Stankovic-Valentin, Nicolas [VerfasserIn]
• Verfasst von: Melchior, Frauke [VerfasserIn]
• Titel: The ubiquitin-like modifier FAT10 interferes with SUMO activation
• Verf.angabe: Annette Aichem, Carolin Sailer, Stella Ryu, Nicola Catone, Nicolas Stankovic-Valentin, Gunter Schmidtke, Frauke Melchior, Florian Stengel & Marcus Groettrup
• E-Jahr: 2019
• Jahr: 01 October 2019
• Umfang: 17 S.
• Fussnoten: Gesehen am 28.10.2019
• Titel Quelle: Enthalten in: Nature Communications
• Ort Quelle: [London] : Nature Publishing Group UK, 2010
• Jahr Quelle: 2019
• Band/Heft Quelle: 10(2019) Artikel-Nummer 4452, 17 Seiten
• ISSN Quelle: 2041-1723
• DOI: doi:10.1038/s41467-019-12430-z
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1680060384

Abstract

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.