ERO1-β, a pancreas-specific disulfide oxidase, promotes insulin biogenesis and glucose homeostasis

Zito, Ester; Chin, King-Tung; Blais, Jaime D.; Harding, Heather P.; Ron, David

doi:10.1083/jcb.200911086

Cited by 206 publications

(194 citation statements)

References 33 publications

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“…Interestingly, Ero1a activity is regulated by the isomerization/reduction of intramolecular disulfide bonds that are exerted by PDI monitoring the redox state of the ER, whereas Ero1b seems to be less tightly regulated and shows higher oxidase activity in vitro (Inaba et al 2010;Tavender and Bulleid 2010a;Wang et al 2011). Surprisingly, a mutant mouse lacking both isoforms of intact Ero1 is viable, even though Ero1 genes in both Saccharomyces cerevisiae and Drosophila are essential (Frand and Kaiser 1998;Tien et al 2008;Zito et al 2010a). Recent studies revealed an alternate cascade centered on peroxiredoxin IV (PRDX4), which is thought to work as a H 2 O 2 reducer (Tavender and Bulleid 2010b).…”

Section: Er Redox Homeostasismentioning

confidence: 99%

“…For example, ERp57 knockout mice showed embryonic lethality, suggesting that ERp57 has a specific role in early development (Garbi et al 2006;Coe et al 2010). Knockout mice of ERdj5, Prdx4, and Ero1a/b (see later section) showed less severe phenotypes, which suggests that their roles can be compensated for by other factors (Iuchi et al 2009;Hosoda et al 2010;Zito et al 2010a). In addition, some ER proteins appear to possess functions outside the ER, such as in mitochondria or nucleus (P5 and ERp57) (Coppari et al 2002;Kimura et al 2008).…”

Section: Disulfide Bond Formationmentioning

confidence: 99%

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Protein Folding and Quality Control in the ER

Araki

Nagata

2011

Cold Spring Harbor Perspectives in Biology

314

285

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The endoplasmic reticulum (ER) uses an elaborate surveillance system called the ER quality control (ERQC) system. The ERQC facilitates folding and modification of secretory and membrane proteins and eliminates terminally misfolded polypeptides through ER-associated degradation (ERAD) or autophagic degradation. This mechanism of ER protein surveillance is closely linked to redox and calcium homeostasis in the ER, whose balance is presumed to be regulated by a specific cellular compartment. The potential to modulate proteostasis and metabolism with chemical compounds or targeted siRNAs may offer an ideal option for the treatment of disease.

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Section: Er Redox Homeostasismentioning

confidence: 99%

Section: Disulfide Bond Formationmentioning

confidence: 99%

Protein Folding and Quality Control in the ER

Araki

Nagata

2011

Cold Spring Harbor Perspectives in Biology

314

285

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“…Both mice and flies lacking Ero1 are viable with only subtle phenotypes (32,33), indicating that ER-localized Trx-like proteins can be oxidized by alternative enzymes (34). The only other known oxidases besides VKOR and Ero1 are the QSOX proteins.…”

Section: Discussionmentioning

confidence: 99%

Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners

Schulman

Wang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

132

159

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Vitamin K epoxide reductase (VKOR) sustains blood coagulation by reducing vitamin K epoxide to the hydroquinone, an essential cofactor for the γ-glutamyl carboxylation of many clotting factors. The physiological redox partner of VKOR remains uncertain, but is likely a thioredoxin-like protein. Here, we demonstrate that human VKOR has the same membrane topology as the enzyme from Synechococcus sp., whose crystal structure was recently determined. Our results suggest that, during the redox reaction, Cys43 in a luminal loop of human VKOR forms a transient disulfide bond with a thioredoxin (Trx)-like protein located in the lumen of the endoplasmic reticulum (ER). We screened for redox partners of VKOR among the large number of mammalian Trx-like ER proteins by testing a panel of these candidates for their ability to form this specific disulfide bond with human VKOR. Our results show that VKOR interacts strongly with TMX, an ER membrane-anchored Trx-like protein with a unique CPAC active site. Weaker interactions were observed with TMX4, a close relative of TMX, and ERp18, the smallest Trx-like protein of the ER. We performed a similar screen with Ero1-α, an ER-luminal protein that oxidizes the Trx-like protein disulfide isomerase. We found that Ero1-α interacts with most of the tested Trx-like proteins, although only poorly with the membrane-anchored members of the family. Taken together, our results demonstrate that human VKOR employs the same electron transfer pathway as its bacterial homologs and that VKORs generally prefer membrane-bound Trx-like redox partners.disulfide bond formation | warfarin | quinone | blood coagulation | electron transfer

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“…Despite its key role in protein folding, Ero1 was found not to be essential in mice (68), suggesting the existence of alternative sources of H 2 O 2 molecules for protein folding. Nox4, which is present in the ER, was proposed as a candidate for such a source.…”

Section: Role Of Prx IV As H 2 O 2 Sensor For Protein Folding In Ermentioning

confidence: 99%

Peroxiredoxin Functions as a Peroxidase and a Regulator and Sensor of Local Peroxides

Rhee

Woo

Kil

et al. 2012

Journal of Biological Chemistry

479

430

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ERO1-β, a pancreas-specific disulfide oxidase, promotes insulin biogenesis and glucose homeostasis

Abstract: ERO1-β has an unexpected and selective function for oxidative protein folding in insulin-producing cells.

Cited by 206 publications

References 33 publications

Protein Folding and Quality Control in the ER

Protein Folding and Quality Control in the ER

Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners

Peroxiredoxin Functions as a Peroxidase and a Regulator and Sensor of Local Peroxides

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