title: Major Histocompatibility Complex (MHC) Class I Processing of the NY-ESO-1 Antigen Is Regulated by Rpn10 and Rpn13 Proteins and Immunoproteasomes following Non-lysine Ubiquitination.
abstract: The supply of MHC class I-restricted peptides is primarily ensured by the degradation of intracellular proteins via the ubiquitin-proteasome system. Depending on the target and the enzymes involved, ubiquitination is a process that may dramatically vary in terms of linkages, length, and attachment sites. Here we identified the unique lysine residue at position 124 of the NY-ESO-1 cancer/testis antigen as the acceptor site for the formation of canonical Lys-48-linkages. Interestingly, a lysine-less form of NY-ESO-1 was as efficient as its wild-type counterpart in supplying the HLA-A*0201-restricted NY-ESO-1157-165 antigenic peptide. In fact, we show that the regulation of NY-ESO-1 processing by the ubiquitin receptors Rpn10 and Rpn13 as a well as by the standard and immunoproteasome is governed by non-canonical ubiquitination on non-lysine sites. In summary, our data underscore the significance of atypical ubiquitination in the modulation of MHC class I antigen processing.
authors.affiliation: From the Institute for Biochemistry, Charité-Universitätsmedizin Berlin, Charité Platz 1/Virchowweg 6, 10117 Berlin, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Golnik
authors.affiliation: From the Institute for Biochemistry, Charité-Universitätsmedizin Berlin, Charité Platz 1/Virchowweg 6, 10117 Berlin, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lehmann
authors.affiliation: From the Institute for Biochemistry, Charité-Universitätsmedizin Berlin, Charité Platz 1/Virchowweg 6, 10117 Berlin, Germany.
authors.forename: Peter-Michael
authors.initials: PM
authors.lastname: Kloetzel
authors.affiliation: From the Institute for Biochemistry, Charité-Universitätsmedizin Berlin, Charité Platz 1/Virchowweg 6, 10117 Berlin, Germany frederic.ebstein@charite.de.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ebstein
mesh_terms: D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000276:immunology*; D016601:RNA-Binding Proteins; D054875:Ubiquitination / Q000235:genetics / Q000276:immunology*
chemical_list: C500781:ADRM1 protein, human; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C498506:PSMD4 protein, human; D016601:RNA-Binding Proteins; D046988:Proteasome Endopeptidase Complex
keywords: antigen processing; proteasome; protein degradation; tumor immunology; ubiquitin