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 Vol 5: Sequential activation of Elk-1-Egr-1-GADD45 by arsenic.


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This article is from Oncotarget, volume 5.AbstractLong-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.



Autor: Shi, Qiwen; Sutariya, Vijaykumar; Bishayee, Anupam; Bhatia, Deepak

Fuente: https://archive.org/







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