title: Involvement of Nrf2 in proteasome inhibition-mediated induction of ORP150 in thyroid cancer cells.
abstract: Oxygen-regulated protein 150 (ORP150) is an inducible ER chaperone by numerous cellular insults and sustains cellular viability. We have previously reported that ORP150 is differentially induced in a panel thyroid cancer cells and represents as an unwanted molecular consequence during exposure to proteasome inhibition. However, the molecular basis for induction of ORP150 by proteasome inhibitors in thyroid cancer cells remains unclear. In the current study, we found that -421/-307 and -243/+53 regions at the ORP150 gene were responsible for its transactivation by MG132 in thyroid cancer cells. Nrf2 directly transactivated the ORP150 gene by direct binding with the -421/-307 region. Nrf2 also indirectly activated OPR150 transcription via facilitating recruitment of ATF4 to the -243/+53 region. Collectively, this study highlights the molecular mechanism by which proteasome inhibition stimulates ORP150 expression via Nrf2 in thyroid cancer cells.
authors.affiliation: Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110001, China.|Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Zong
authors.affiliation: Department of Endocrinology & Metabolism, The 1st Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Zhen-Xian
authors.initials: ZX
authors.lastname: Du
authors.affiliation: Department of Geriatrics, The 1st Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110001, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110001, China.
authors.forename: Ming-Xin
authors.initials: MX
authors.lastname: An
authors.affiliation: Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110001, China.
authors.forename: Si
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110001, China.
authors.forename: Han-Bing
authors.initials: HB
authors.lastname: Yao
authors.affiliation: Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110001, China.|Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.
authors.forename: Hua-Qin
authors.initials: HQ
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry*; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D018840:HSP70 Heat-Shock Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D061988:Proteasome Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C050087:oxygen-regulated proteins; D046988:Proteasome Endopeptidase Complex
keywords: Nrf2; ORP150; proteasome inhibitor; thyroid cancer