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: Kazuharu Kukita, Yasuaki Tamura, Tsutomu Tanaka, Toshimitsu Kajiwara, Goro Kutomi, Keita Saito, Koichi Okuya, Akari Takaya, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Toshihiko Torigoe, Tomohisa Furuhata, Koichi Hirata, Noriyuki Sato
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 194 Issue 10 Pg. 4988-96 (May 15 2015) ISSN: 1550-6606 [Electronic] United States
• PMID: 25870246 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 by The American Association of Immunologists, Inc.

Chemical References

• Histocompatibility Antigens Class I
• Membrane Glycoproteins
• ERO1A protein, human
• Oxidoreductases

Topics

• Antigen Presentation (immunology)
• Blotting, Western
• CD8-Positive T-Lymphocytes (immunology)
• Cell Line, Tumor
• Colonic Neoplasms (immunology, metabolism, pathology)
• Flow Cytometry
• Gene Expression Regulation, Neoplastic (immunology)
• Histocompatibility Antigens Class I (biosynthesis)
• Humans
• Immunohistochemistry
• Immunoprecipitation
• Membrane Glycoproteins (immunology, metabolism)
• Oxidation-Reduction
• Oxidoreductases (immunology, metabolism)
• Protein Folding
• Protein Structure, Tertiary
• Real-Time Polymerase Chain Reaction