Oncotarget

Research Papers:

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

Zhi-Hong Zong, Zhen-Xian Du, Hai-Yan Zhang, Chao Li, Ming-Xin An, Si Li, Han-Bing Yao and Hua-Qin Wang _

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Oncotarget. 2016; 7:3416-3426. https://doi.org/10.18632/oncotarget.6636

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Abstract

Zhi-Hong Zong1,2, Zhen-Xian Du3, Hai-Yan Zhang4, Chao Li1, Ming-Xin An1, Si Li1, Han-Bing Yao1, Hua-Qin Wang1,2

1Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110001, China

2Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China

3Department of Endocrinology & Metabolism, The 1st Affiliated Hospital, China Medical University, Shenyang 110001, China

4Department 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.


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