Role of proteasome subtypes in the processing of tumor antigens and the degradation of oxidized proteins. (October 2022)

• Record Type: Journal Article
• Authors: Van den Eynde, Benoit; Habib, Joanna Abi; Vigneron, Nathalie; De Plaen, Etienne; Stroobant, Vincent; Bousquet, Marie-Pierre; Messens, Joris
• Is Part Of: Molecular immunology. Volume 150(2022)
• Page Start: 5
• Publication Date: 2022-10
• Subjects: Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2022.05.026
• Languages: English
• ISSNs: 0161-5890

Abstract

Abstract : Conditions such as inflammation or hypoxia often lead to the release of reactive oxygen species, which can induce post-translational modifications of protein residues, impairing protein structure and function. Such damaged proteins are targeted for degradation by the proteasome, a large protease complex that maintains protein homeostasis and produces peptides binding to MHC class I molecules. How oxidized proteins are recognized by the proteasome and which proteasome subtypes are best suited to degrade oxidized proteins is still unclear. Here, we show that oxidized calmodulin and hemoglobin are prominently degraded by 20S proteasomes containing the β5i catalytic subunit, i.e. immuneproteasomes and intermediate proteasomes β5i and β1iβ5i. Recognition of oxidized proteins appears to be dictated by their altered structure rather than the exposure of hydrophobic patches or oxidized residues. In contrast, the four proteasome subtypes proved equally efficient to degrade ubiquitinated proteins in a cellular assay. Interestingly, the presence of an oxidized methionine in the protein sequence appears to modify proteasome cleavage sites, thereby potentially altering the peptide repertoire.