title: Cancer-Associated Oxidase ERO1-α Regulates the Expression of MHC Class I Molecule via Oxidative Folding.
abstract: 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.
authors: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; and Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors: Kazuharu
authors: K
authors: Kukita
authors: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; and ytamura3566@gmail.com.
authors: Yasuaki
authors: http://orcid.org/0000-0002-0112-8730
authors: Y
authors: Tamura
authors: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; and.
authors: Tsutomu
authors: T
authors: Tanaka
authors: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; and.
authors: Toshimitsu
authors: T
authors: Kajiwara
authors: Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors: Goro
authors: G
authors: Kutomi
authors: Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors: Keita
authors: K
authors: Saito
authors: Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors: Koichi
authors: K
authors: Okuya
authors: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; and.
authors: Akari
authors: A
authors: Takaya
authors: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; and.
authors: Takayuki
authors: T
authors: Kanaseki
authors: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; and.
authors: Tomohide
authors: T
authors: Tsukahara
authors: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; and.
authors: Yoshihiko
authors: Y
authors: Hirohashi
authors: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; and.
authors: Toshihiko
authors: T
authors: Torigoe
authors: Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors: Tomohisa
authors: T
authors: Furuhata
authors: Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors: Koichi
authors: K
authors: Hirata
authors: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; and.
authors: Noriyuki
authors: N
authors: Sato
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000276:immunology / Q000378:metabolism*; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; C405327:ERO1A protein, human; D010088:Oxidoreductases