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The ubiquitin-like modifier FAT10 interferes with SUMO activation

Author

Listed:
  • Annette Aichem

    (Biotechnology Institute Thurgau at the University of Konstanz
    University of Konstanz)

  • Carolin Sailer

    (University of Konstanz)

  • Stella Ryu

    (Biotechnology Institute Thurgau at the University of Konstanz
    University of Konstanz)

  • Nicola Catone

    (Biotechnology Institute Thurgau at the University of Konstanz)

  • Nicolas Stankovic-Valentin

    (DKFZ-ZMBH Alliance)

  • Gunter Schmidtke

    (University of Konstanz)

  • Frauke Melchior

    (DKFZ-ZMBH Alliance)

  • Florian Stengel

    (University of Konstanz)

  • Marcus Groettrup

    (Biotechnology Institute Thurgau at the University of Konstanz
    University of Konstanz)

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.

Suggested Citation

  • Annette Aichem & Carolin Sailer & Stella Ryu & Nicola Catone & Nicolas Stankovic-Valentin & Gunter Schmidtke & Frauke Melchior & Florian Stengel & Marcus Groettrup, 2019. "The ubiquitin-like modifier FAT10 interferes with SUMO activation," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12430-z
    DOI: 10.1038/s41467-019-12430-z
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