Marcus Groettrup †02.06.2022
The substrates of FAT10ylation and their proteolytic targeting – Identification of FAT10 specific E3 ligases
The cytokine-inducible ubiquitin-like modifier FAT10 is getting covalently conjugated to hundreds of proteins which targets them for degradation by the 26S proteasome. Recently, we have shown that the E1 enzyme UBA6 and the E2 enzyme USE1 are required for FAT10 conjugate formation. All well investigated ubiquitin-like modifiers use E3 ligases for catalysing substrate modification. Therefore, we hypothesize that E3 ligases exist also for FAT10. In this project we wish to identify and validate putative E3 ligases of the FAT10 conjugation cascade using five complementary approaches. By identifying E3 ligases for FAT10 we hope to elucidate how substrate selectivity is achieved in FAT10-mediated proteasomal degradation.