Involvement of Nrf2 in proteasome inhibition-mediated induction of ORP150 in thyroid cancer cells

Autor: Hua-Qin Wang, Zhen-Xian Du, Han-Bing Yao, Chao Li, Ming-Xin An, Si Li, Zhi-Hong Zong, Haiyan Zhang
Rok vydání: 2015
Předmět:
0301 basic medicine
Transcriptional Activation
Chromatin Immunoprecipitation
Proteasome Endopeptidase Complex
NF-E2-Related Factor 2
Blotting
Western
Real-Time Polymerase Chain Reaction
Nrf2
Immunoenzyme Techniques
03 medical and health sciences
chemistry.chemical_compound
Transactivation
MG132
medicine
Tumor Cells
Cultured
thyroid cancer
Humans
HSP70 Heat-Shock Proteins
RNA
Messenger
Thyroid Neoplasms
RNA
Small Interfering
Promoter Regions
Genetic
Thyroid cancer
business.industry
Reverse Transcriptase Polymerase Chain Reaction
proteasome inhibitor
ATF4
ORP150
medicine.disease
030104 developmental biology
Real-time polymerase chain reaction
Oncology
chemistry
Proteasome
Immunology
Proteasome inhibitor
Cancer research
business
Chromatin immunoprecipitation
Proteasome Inhibitors
medicine.drug
Research Paper
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: // Zhi-Hong Zong 1, 2 , Zhen-Xian Du 3 , Hai-Yan Zhang 4 , Chao Li 1 , Ming-Xin An 1 , Si Li 1 , Han-Bing Yao 1 , Hua-Qin Wang 1, 2 1 Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110001, China 2 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 3 Department of Endocrinology & Metabolism, The 1st Affiliated Hospital, China Medical University, Shenyang 110001, China 4 Department of Geriatrics, The 1st Affiliated Hospital, China Medical University, Shenyang 110001, China Correspondence to: Hua-Qin Wang, e-mail: wanghq_doctor@hotmail.com Keywords: proteasome inhibitor, Nrf2, ORP150, thyroid cancer Received: July 05, 2015 Accepted: November 21, 2015 Published: December 18, 2015 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.
Databáze: OpenAIRE
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