Conjugation of the ubiquitin activating enzyme UBE1 with the ubiquitin-like modifier FAT10 targets it for proteasomal degradation

PloS One
Johanna BialasAnnette Aichem

Abstract

The ubiquitin-like modifier HLA-F adjacent transcript 10 (FAT10) directly targets its substrates for proteasomal degradation by becoming covalently attached via its C-terminal diglycine motif to internal lysine residues of its substrate proteins. The conjugation machinery consists of the bispecific E1 activating enzyme Ubiquitin-like modifier activating enzyme 6 (UBA6), the likewise bispecific E2 conjugating enzyme UBA6-specific E2 enzyme 1 (USE1), and possibly E3 ligases. By mass spectrometry analysis the ubiquitin E1 activating enzyme ubiquitin-activating enzyme 1 (UBE1) was identified as putative substrate of FAT10. Here, we confirm that UBE1 and FAT10 form a stable non-reducible conjugate under overexpression as well as under endogenous conditions after induction of endogenous FAT10 expression with proinflammatory cytokines. FAT10ylation of UBE1 depends on the diglycine motif of FAT10. By specifically downregulating FAT10, UBA6 or USE1 with siRNAs, we show that UBE1 modification depends on the FAT10 conjugation pathway. Furthermore, we confirm that UBE1 does not act as a second E1 activating enzyme for FAT10 but that FAT10ylation of UBE1 leads to its proteasomal degradation, implying a putative regulatory role of FAT10 in t...Continue Reading

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Citations

Sep 27, 2015·Experimental and Molecular Pathology·Murali GanesanNatalia A Osna
Oct 4, 2015·Trends in Molecular Medicine·Ewout J N Groen, Thomas H Gillingwater
Jun 29, 2018·Genes·Shuaichen LiuCaroline G L Lee
Feb 6, 2019·The Journal of Biological Chemistry·Johanna BialasMarcus Groettrup
May 10, 2019·International Journal of Molecular Sciences·Fengting Wang, Bo Zhao
Oct 3, 2019·Nature Communications·Annette AichemMarcus Groettrup
May 27, 2020·Essays in Biochemistry·Isabelle C Da Costa, Christine K Schmidt
Jun 18, 2020·Journal of Cell Science·Richard SchregleMarcus Groettrup
May 26, 2017·Scientific Reports·Yung-Cheng ShinShih-Chung Chang
Jul 29, 2020·Journal of Cell Science·Annette Aichem, Marcus Groettrup
Aug 21, 2020·The Journal of Biological Chemistry·Annika N BoehmAnnette Aichem
Dec 12, 2020·Journal of Molecular and Cellular Cardiology·Rong WanKui Hong

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Methods Mentioned

BETA
co-immunoprecipitations
immunoprecipitation
co-immunoprecipitation
transfection

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