{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ERO1B is an endoplasmic reticulum–localized oxidase that drives disulfide bond formation by oxidizing protein disulfide isomerase (PDI), thereby facilitating the oxidative folding of secreted proteins. In professional secretory cells—most notably in pancreatic β cells and stomach chief cells—ERO1B is expressed at high levels to meet the large demands for efficient protein folding. Notably, disruption of ERO1B function in β cells selectively impairs proinsulin oxidative folding and predisposes to glucose intolerance, highlighting its critical role in insulin maturation and overall metabolic homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In contrast to its paralogue ERO1α, ERO1B is generally more active and appears to be less stringently regulated by intramolecular disulfide switches. This relatively “loose” regulation enables ERO1B to generate the oxidizing power needed in tissues with high secretory activity, yet its overexpression must be finely tuned; excessive ERO1B can provoke endoplasmic reticulum stress, alter unfolded protein response gene expression, and ultimately compromise secretory function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, aberrant levels of ERO1B may contribute to disease pathology. In pancreatic β cells, for instance, while appropriate ERO1B expression is required for normal insulin biogenesis, its dysregulation is associated with ER redox imbalance and impaired insulin secretion, thereby linking fine-tuned ERO1B activity to the pathogenesis of diabetes mellitus."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, differential expression of ERO1B has been observed in certain pancreatic tumors, suggesting potential utility as a biomarker of disease state."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, the current findings underscore that ERO1B is indispensable for maintaining ER redox homeostasis in high-output secretory tissues by ensuring the proper oxidative folding of client proteins. Its activity and expression levels are tightly linked to cellular function and, when perturbed, may have far-reaching metabolic and pathological consequences."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ester Zito, King-Tung Chin, Jaime Blais, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ERO1-beta, a pancreas-specific disulfide oxidase, promotes insulin biogenesis and glucose homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200911086"}], "href": "https://doi.org/10.1083/jcb.200911086"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20308425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20308425"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sanjika Dias-Gunasekara, Jacob Gubbens, Marcel van Lith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tissue-specific expression and dimerization of the endoplasmic reticulum oxidoreductase Ero1beta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M505023200"}], "href": "https://doi.org/10.1074/jbc.M505023200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16012172"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16012172"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lei Wang, Li Zhu, Chih-chen Wang "}, {"type": "b", "children": [{"type": "t", "text": "The endoplasmic reticulum sulfhydryl oxidase Ero1β drives efficient oxidative protein folding with loose regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20101357"}], "href": "https://doi.org/10.1042/BJ20101357"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21091435"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21091435"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Motoharu Awazawa, Takashi Futami, Michinori Sakada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deregulation of pancreas-specific oxidoreductin ERO1β in the pathogenesis of diabetes mellitus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01647-13"}], "href": "https://doi.org/10.1128/MCB.01647-13"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24469402"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24469402"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Junjie Xie, Yi Zhu, Hao Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Immunohistochemical Evaluation of Solid Pseudopapillary Tumors of the Pancreas and Pancreatic Neuroendocrine Tumors Reveals ERO1Lβ as a New Biomarker."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Medicine (Baltimore) (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MD.0000000000002509"}], "href": "https://doi.org/10.1097/MD.0000000000002509"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26765469"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26765469"}]}]}]}