The FAT10- and ubiquitin-dependent degradation machineries exhibit common and distinct requirements for MHC class I antigen presentation.

Cellular and Molecular Life Sciences : CMLS
Frédéric EbsteinPeter-Michael Kloetzel

Abstract

Like ubiquitin (Ub), the ubiquitin-like protein FAT10 can serve as a signal for proteasome-dependent protein degradation. Here, we investigated the contribution of FAT10 substrate modification to MHC class I antigen presentation. We show that N-terminal modification of the human cytomegalovirus-derived pp65 antigen to FAT10 facilitates direct presentation and dendritic cell-mediated cross-presentation of the HLA-A2 restricted pp65(495-503) epitope. Interestingly, our data indicate that the pp65 presentation initiated by either FAT10 or Ub partially relied on the 19S proteasome subunit Rpn10 (S5a). However, FAT10 distinguished itself from Ub in that it promoted a pp65 response which was not influenced by immunoproteasomes or PA28. Further divergence occurred at the level of Ub-binding proteins with NUB1 supporting the pp65 presentation arising from FAT10, while it exerted no effect on that initiated by Ub. Collectively, our data establish FAT10 modification as a distinct and alternative signal for facilitated MHC class I antigen presentation.

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Citations

Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Allon CanaanSherman M Weissman
May 20, 2015·Molecular Immunology·Michael BaslerMarcus Groettrup
Jan 22, 2013·Biochimica Et Biophysica Acta·Gunter SchmidtkeMarcus Groettrup
Nov 26, 2014·Proceedings of the National Academy of Sciences of the United States of America·Steven Setiawan ThengCaroline G Lee
Dec 8, 2016·FEBS Letters·Valentina SpinnenhirnMarcus Groettrup
Jun 18, 2020·Journal of Cell Science·Richard SchregleMarcus Groettrup
Jul 29, 2020·Journal of Cell Science·Annette Aichem, Marcus Groettrup
Sep 25, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stefanie BuergerMichael Basler
Jul 21, 2020·European Journal of Immunology·Tobias HeldMarcus Groettrup
Sep 19, 2020·Clinica Chimica Acta; International Journal of Clinical Chemistry·Kai ZhangLanfang Li

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Methods Mentioned

BETA
FCS
PCR
transfection
protein assay
ELISA
immunoprecipitation

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