title: Investigations into the auto-FAT10ylation of the bispecific E2 conjugating enzyme UBA6-specific E2 enzyme 1.
abstract: The cytokine-inducible ubiquitin-like modifier HLA-F adjacent transcript 10 (FAT10) targets its substrates for degradation by the proteasome. FAT10 is conjugated to its substrates via the bispecific, ubiquitin-activating and FAT10-activating enzyme UBA6, the likewise bispecific conjugating enzyme UBA6-specific E2 enzyme 1 (USE1), and possibly E3 ligases. By MS analysis, we found that USE1 undergoes self-FAT10ylation in cis, mainly at Lys323. Mutation of Lys323 to an arginine did not abolish auto-FAT10ylation of USE1, but every other lysine could instead be modified with FAT10. Similarly to bulk FAT10 substrates, FAT10ylation of USE1 accelerated its proteasomal degradation. Interestingly, the USE1-FAT10 conjugate continued to be an active E2 enzyme, because both FAT10 and ubiquitin could still be thioester-linked to the USE1-FAT10 conjugate. We therefore suggest that the major function of USE1 auto-FAT10ylation is to serve as a negative feedback mechanism to limit the conjugation of FAT10 upon its cytokine-mediated induction by reducing the amount of USE1 through proteasomal degradation of the USE1-FAT10 conjugate.
  •USE1 physically interacts with FAT10 by anti bait coimmunoprecipitation (View interaction) •USE1 physically interacts with FAT10 by anti tag coimmunoprecipitation (View interaction).
authors: Biotechnology Institute Thurgau at the University of Konstanz, Kreuzlingen, Switzerland.
authors: Annette
authors: A
authors: Aichem
authors: Nicola
authors: N
authors: Catone
authors: Marcus
authors: M
authors: Groettrup
mesh_terms: D025461:Feedback, Physiological; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis; D050600:SNARE Proteins; D054875:Ubiquitination; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins
chemical_list: D050600:SNARE Proteins; C109184:UBD protein, human; D014452:Ubiquitins; C521756:Use1 protein, human; D033921:Vesicular Transport Proteins; D046988:Proteasome Endopeptidase Complex
keywords: FAT10; UBA6-specific E2 enzyme 1 (USE1); proteasome