Research Papers:

Sequential activation of Elk-1/Egr-1/GADD45α by arsenic

Qiwen Shi, Vijaykumar Sutariya, Anupam Bishayee and Deepak Bhatia _

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Oncotarget. 2014; 5:3862-3870. https://doi.org/10.18632/oncotarget.1995

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Qiwen Shi1,2, Vijaykumar Sutariya3, Anupam Bishayee4 and Deepak Bhatia1

1 Department of Pharmaceutical Sciences, Northeast Ohio Medical University (NEOMED), Rootstown, Ohio, USA

2 School of Biomedical Sciences, Kent State University, Kent, Ohio, USA

3 Department of Pharmaceutical Sciences, University of South Florida, Tampa, Florida, USA

4 Department of Pharmaceutical Sciences, American University of Health Sciences, Signal Hill, California, USA


Deepak Bhatia, email:

Keywords: Egr-1; GADD45α; Arsenic; MAP kinase; Elk-1

Received: February 14, 2014 Accepted: May 20, 2014 Published: May 22, 2014


Long-term exposure to arsenic, an environmental contaminant, leads to increased risks of cancers. In the present study, we investigated the sequential regulation of Elk-1 and Egr-1 on As3+-induced GADD45α, an effector of G2/M checkpoint. We found that As3+ transcriptionally induced both Elk-1 and Egr-1, and NF-κB binding site was necessary for As3+-induced Egr-1 promoter activity. However, specific inhibition of JNK, ERK, and Elk-1 inhibited Egr-1 induction. Furthermore, silencing of Egr-1 downregulated As3+-induced expression of GADD45α and ChIP assay confirmed the direct binding of Egr-1 to GADD45α promoter. Taken together, our data indicated that the increase of GADD45α in response to As3+ was mediated sequentially by Elk-1 and Egr-1.

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