NCBI Summary:
This gene encodes the transmembrane protein kinase inositol-requiring enzyme 1. The encoded protein contains two functional catalytic domains, a serine/threonine-protein kinase domain and an endoribonuclease domain. This protein functions as a sensor of unfolded proteins in the endoplasmic reticulum (ER) and triggers an intracellular signaling pathway termed the unfolded protein response (UPR). The UPR is an ER stress response that is conserved from yeast to mammals and activates genes involved in degrading misfolded proteins, regulating protein synthesis and activating molecular chaperones. This protein specifically mediates the splicing and activation of the stress response transcription factor X-box binding protein 1. [provided by RefSeq, Aug 2017]
General function
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Cellular localization
Other Membrane, ER
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Ovarian function
Follicle atresia, Oocyte maturation, Early embryo development
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Human placenta-derived mesenchymal stem cells inhibit apoptosis of granulosa cells induced by IRE1α pathway in autoimmune POF mice. Li H et al. (2019) Previous studies have shown that the ovarian failure in autoimmune-induced premature ovarian failure (POF) mice could be improved by the transplantation of human placenta-derived mesenchymal stem cells (hPMSCs); however, the protective mechanism of hPMSCs transplantation on ovarian dysfunction remains unclear. Ovarian dysfunction is closely related to the apoptosis of granulosa cells (GCs). To determine the effects of hPMSCs transplantation on GCs apoptosis, an autoimmune POF mice model was established with zonapellucida glycoprotein 3 (ZP3) peptide. It is reported that the inositol-requiring enzyme 1α (IRE1α) and its downstream molecules play a central role in the endoplasmic reticulum (ER) stress-induced apoptosis pathway. So the aim of this study is to investigate whether hPMSCs transplantation attenuated GCs apoptosis via inhibiting ER stress IRE1α signaling pathway. The ovarian dysfunction, follicular dysplasia and GCs apoptosis were observed in the POF mice. And the IRE1α pathway was activated in ovaries of POF mice, as demonstrated by, increased X-box binding protein 1 (XBP1), up-regulated 78kDa glucose-regulated protein (GRP78) and Caspase-12. Following transplantation of hPMSCs, the ovarian structure and function were significantly improved in POF mice. In addition, the GCs apoptosis were obviously attenuated and IRE1α pathway was significantly inhibited. Transplantation of hPMSCs suppressed GCs apoptosis induced by ER stress IRE1α signaling pathway in POF mice, which might contribute to the hPMSCs transplantation-mediating ovarian function recovery. This article is protected by copyright. All rights reserved.//////////////////
Expression regulated by
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Ovarian localization
Cumulus, Granulosa
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Evidence of the activation of unfolded protein response in granulosa and cumulus cells during follicular growth and maturation. Harada M et al. (2015) The objective of the present study is to investigate whether unfolded protein response (UPR), activated by endoplasmic reticulum (ER) stress, in granulosa cells (GC) and cumulus cells (CC) is involved in the process of follicular growth and maturation. First, to examine the presence of UPR in growing follicles, the expression of spliced form of X-box-binding protein 1 (XBP1(S)) and heat shock 70 kDa protein 5 (HSPA5) mRNA, typical UPR genes, in mice ovaries were examined by in situ hybridization. GC of later stage than large secondary follicles expressed both XBP1(S) and HSPA5 mRNA, which was accompanied with the activation of ER stress sensor proteins, inositol-requiring enzyme 1 (IRE1) and double-stranded RNA-activated protein kinase-like ER kinase (PERK), confirmed by immunohistochemistry. Next, to examine the association between the fertilization capacity of oocytes and the expression levels of UPR genes in surrounding CC, human CC were collected from patients undergoing ICSI. The expression levels of XBP1(S) mRNA, quantified by RT-PCR, in CC enclosing human oocytes achieving fertilization were two-fold higher, than those in CC enclosing oocytes without fertilization capacity. In conclusion, UPR is activated during follicular growth and suggested to be involved in the process of follicular growth and maturation.//////////////////