Role of the ERO1-PDI interaction in oxidative protein folding and disease

被引：119

作者：

Shergalis, Andrea G. ^{[1
]}

Hu, Shuai ^{[1
,2
]}

Bankhead, Armand I. I. I. I. I. I. ^{[2
,3
]}

Neamati, Nouri ^{[1
]}

机构：

[1] Univ Michigan, Coll Pharm, Dept Med Chem, Rogel Canc Ctr, North Campus Res Complex, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Computat Med & Bioinformat, Med Sch, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Biostat, Sch Publ Hlth, Ann Arbor, MI 48109 USA

来源：

PHARMACOLOGY & THERAPEUTICS | 2020年 / 210卷

基金：

美国国家卫生研究院;

关键词：

Protein folding; Targeted therapy; Cancer; Endoplasmic reticulum Oxidase; Protein disulfide Isomerase; Gene expression; ENDOPLASMIC-RETICULUM STRESS; DISULFIDE-BOND FORMATION; OXIDOREDUCTIN; 1-ALPHA; ISOMERASE INHIBITORS; CONNECTIVITY MAP; POOR-PROGNOSIS; ER-STRESS; ERO1-ALPHA; EXPRESSION; CALCIUM;

D O I：

10.1016/j.pharmthera.2020.107525

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Protein folding in the endoplasmic reticulum is an oxidative process that relies on protein disulfide isomerase (PDI) and endoplasmic reticulum oxidase 1 (ERO1). Over 30% of proteins require the chaperone PDI to promote disulfide bond formation. PDI oxidizes cysteines in nascent polypeptides to form disulfide bonds and can also reduce and isomerize disulfide bonds. ERO1 recycles reduced PDI family member PDIA1 using a FAD cofactor to transfer electrons to oxygen. ERO1 dysfunction critically affects several diseases states. Both ERO1 and PDIA1 are overexpressed in cancers and implicated in diabetes and neurodegenerative diseases. Cancer-associated ERO1 promotes cell migration and invasion. Furthermore, the ERO1-PDIA1 interaction is critical for epithelial-to-mesenchymal transition. Co-expression analysis of ERO1A gene expression in cancer patients demonstrated that ERO1A is significantly upregulated in lung adenocarcinoma (LUAD), glioblastoma and low-grade glioma (GBMLGG), pancreatic ductal adenocarcinoma (PAAD), and kidney renal papillary cell carcinoma (KIRP) cancers. ERO1. knockdown gene signature correlates with knockdown of cancer signaling proteins including IGF1R, supporting the search for novel, selective ERO1 inhibitors for the treatment of cancer. In this review, we explore the functions of ERO1 and PDI to support inhibition of this interaction in cancer and other diseases. (C) 2020 Elsevier Inc. All rights reserved.

引用

页数：16

共 172 条

[1] ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family [J].