Cancer-Associated Oxidase ERO1-α Regulates the Expression of MHC Class I Molecule via Oxidative Folding
| Autor: | Toshimitsu Kajiwara, Goro Kutomi, Yasuaki Tamura, Keita Saito, Tsutomu Tanaka, Noriyuki Sato, Takayuki Kanaseki, Yoshihiko Hirohashi, Koichi Hirata, Tomohisa Furuhata, Kazuharu Kukita, Koichi Okuya, Akari Takaya, Tomohide Tsukahara, Toshihiko Torigoe |
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| Rok vydání: | 2013 |
| Předmět: |
Protein Folding
CD74 Immunology Blotting Western C-C chemokine receptor type 7 Biology CD8-Positive T-Lymphocytes Real-Time Polymerase Chain Reaction Calnexin Cell Line Tumor MHC class I Immunology and Allergy Humans Immunoprecipitation Protein disulfide-isomerase Antigen Presentation Membrane Glycoproteins Antigen processing Histocompatibility Antigens Class I Transporter associated with antigen processing MHC restriction Flow Cytometry Immunohistochemistry Protein Structure Tertiary Gene Expression Regulation Neoplastic Biochemistry Colonic Neoplasms biology.protein Oxidoreductases Oxidation-Reduction |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1550-6606 |
| Popis: | ERO1-α is an oxidizing enzyme that exists in the endoplasmic reticulum and is induced under hypoxia. It reoxidizes the reduced form of protein disulfide isomerase that has oxidized target proteins. We found that ERO1-α is overexpressed in a variety of tumor types. MHC class I H chain (HC) has two disulfide bonds in the α2 and α3 domains. MHC class I HC folding is linked to the assembly of MHC class I molecules because only fully disulfide-bonded class I HCs efficiently assemble with β2-microglobulin. In this study, we show that ERO1-α associates with protein disulfide isomerase, calnexin, and immature MHC class I before being incorporated into the TAP-1–associated peptide-loading complex. Importantly, ERO1-α regulates the redox state as well as cell surface expression of MHC class I, leading to alteration of susceptibility by CD8+ T cells. Similarly, the ERO1-α expression within cancer cells was associated with the expression level of MHC class I in colon cancer tissues. Thus, the cancer-associated ERO1-α regulates the expression of the MHC class I molecule via oxidative folding |
| Databáze: | OpenAIRE |
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