Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/12083
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dc.contributor.authorİlhan, Recepen_US
dc.contributor.authorÜner, Göklemen_US
dc.contributor.authorYılmaz, Sinemen_US
dc.contributor.authorAtalay Sahar, Esraen_US
dc.contributor.authorÇaylı, Sevilen_US
dc.contributor.authorErzurumlu, Yalçınen_US
dc.contributor.authorGözen, Oğuzen_US
dc.contributor.authorBallar Kırmızıbayrak, Peteken_US
dc.date.accessioned2022-06-22T08:06:18Z-
dc.date.available2022-06-22T08:06:18Z-
dc.date.issued2022-12-
dc.identifier.urihttps://doi.org/10.1038/s41598-022-04821-y-
dc.identifier.urihttps://hdl.handle.net/11147/12083-
dc.descriptionThis research was funded by the Scientific and Technological Research Council of Turkey (TUBITAK, SBAG-116S444) and by Ege University internal funds (16/ECZ/006). We thank the Pharmaceutical Sciences Research Centre (FABAL, Ege University, Faculty of Pharmacy) and Biotechnology and Bioengineering Application and Research Centre (BIYOMER, İzmir Institute of Technology) for equipment support, Burcu ERBAYKENT TEPE-DELEN, Selin GÜNAL, and Aysegül KAYMAK for their technical assistance and scientific support.en_US
dc.description.abstractEndoplasmic reticulum-associated degradation (ERAD) is a well-characterized mechanism of protein quality control by removal of misfolded or unfolded proteins. The tight regulation of ERAD is critical for protein homeostasis as well as lipid metabolism. Although the mechanism is complex, all ERAD branches converge on p97/VCP, a key protein in the retrotranslocation step. The multifunctionality of p97/VCP relies on its multiple binding partners, one of which is the endogenous ERAD inhibitor, SVIP (small VCP-interacting protein). As SVIP is a promising target for the regulation of ERAD, we aimed to assess its novel physiological roles. We revealed that SVIP is highly expressed in the rat adrenal gland, especially in the cortex region, at a consistently high level during postnatal development, unlike the gradual increase in expression seen in developing nerves. Steroidogenic stimulators caused a decrease in SVIP mRNA expression and increase in SVIP protein degradation in human adrenocortical H295R cells. Interestingly, silencing of SVIP diminished cortisol secretion along with downregulation of steroidogenic enzymes and proteins involved in cholesterol uptake and cholesterol biosynthesis. A certain degree of SVIP overexpression mainly increased the biosynthesis of cortisol as well as DHEA by enhancing the expression of key steroidogenic proteins, whereas exaggerated overexpression led to apoptosis, phosphorylation of eIF2α, and diminished adrenal steroid hormone biosynthesis. In conclusion, SVIP is a novel regulator of adrenal cortisol and DHEA biosynthesis, suggesting that alterations in SVIP expression levels may be involved in the deregulation of steroidogenic stimulator signaling and abnormal adrenal hormone secretion.en_US
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofScientific Reportsen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectERADen_US
dc.subjectProteinsen_US
dc.subjectDHEA biosynthesisen_US
dc.titleNovel regulation mechanism of adrenal cortisol and DHEA biosynthesis via the endogen ERAD inhibitor small VCP-interacting proteinen_US
dc.typeArticleen_US
dc.authorid0000-0003-4970-4837en_US
dc.institutionauthorÜner, Göklemen_US
dc.departmentİzmir Institute of Technology. Bioengineeringen_US
dc.identifier.wosWOS:000744120000036en_US
dc.identifier.scopus2-s2.0-85123126503en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1038/s41598-022-04821-y-
dc.identifier.pmid35042898-
dc.contributor.affiliationEge Üniversitesien_US
dc.contributor.affiliationIzmir Institute of Technologyen_US
dc.contributor.affiliationEge Üniversitesien_US
dc.contributor.affiliationEge Üniversitesien_US
dc.contributor.affiliationAnkara Yıldırım Beyazıt Üniversitesien_US
dc.contributor.affiliationEge Üniversitesien_US
dc.contributor.affiliationEge Üniversitesien_US
dc.contributor.affiliationEge Üniversitesien_US
dc.identifier.pmcidPMC8766438-
dc.relation.issn2045-2322en_US
dc.description.volume12en_US
dc.description.issue1en_US
dc.identifier.scopusqualityQ1-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextWith Fulltext-
item.languageiso639-1en-
item.grantfulltextopen-
item.openairetypeArticle-
crisitem.author.dept01. Izmir Institute of Technology-
Appears in Collections:Bioengineering / Biyomühendislik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
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