title: The cytoplasmic peptidase DPP9 is rate-limiting for degradation of proline-containing peptides.
abstract: Protein degradation is an essential process that continuously takes place in all living cells. Regulated degradation of most cellular proteins is initiated by proteasomes, which produce peptides of varying length. These peptides are rapidly cleaved to single amino acids by cytoplasmic peptidases. Proline-containing peptides pose a specific problem due to structural constrains imposed by the pyrrolidine ring that prevents most peptidases from cleavage. Here we show that DPP9, a poorly characterized cytoplasmic prolyl-peptidase, is rate-limiting for destruction of proline-containing substrates both in cell extracts and in intact cells. We identified the first natural substrate for DPP9, the RU1(34-42) antigenic peptide (VPYGSFKHV). RU1(34-42) is degraded in vitro by DPP9, and down-regulation of DPP9 in intact cells results in increased presentation of this antigen. Together our findings demonstrate an important role for DPP9 in peptide turnover and antigen presentation.
authors: Department of Biochemistry 1, Faculty of Medicine, Georg-August-University of Göttingen, Humboldtallee 23, 37073 Göttingen, Germany. rgeiss@gwdg.de
authors: Ruth
authors: R
authors: Geiss-Friedlander
authors: Nicolas
authors: N
authors: Parmentier
authors: Ulrike
authors: U
authors: Möller
authors: Henning
authors: H
authors: Urlaub
authors: Benoit J
authors: BJ
authors: Van den Eynde
authors: Frauke
authors: F
authors: Melchior
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001483:Base Sequence; D002460:Cell Line; D003593:Cytoplasm / Q000201:enzymology*; D003600:Cytosol / Q000378:metabolism; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism*; D011392:Proline / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D015234:HLA-A Antigens; D009842:Oligopeptides; D011392:Proline; C471241:DPP9 protein, human; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases