Sequential activation of Elk-1/Egr-1/GADD45alpha by arsenic.

Title

Sequential activation of Elk-1/Egr-1/GADD45alpha by arsenic.

Creator

Shi Qiwen; Sutariya Vijaykumar; Bishayee Anupam; Bhatia Deepak

Publisher

Oncotarget

Date

2014
2014-06

Description

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 GADD45alpha, an effector of G2/M checkpoint. We found that As3+ transcriptionally induced both Elk-1 and Egr-1, and NF-kappaB 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 GADD45alpha and ChIP assay confirmed the direct binding of Egr-1 to GADD45alpha promoter. Taken together, our data indicated that the increase of GADD45alpha in response to As3+ was mediated sequentially by Elk-1 and Egr-1.

Subject

Humans; Cell Line; Proto-Oncogene Proteins c-akt/metabolism; MAP Kinase Signaling System; Arsenic/*pharmacology; Bronchi/cytology/drug effects/metabolism; Cell Cycle Proteins/biosynthesis/genetics/*metabolism; Early Growth Response Protein 1/biosynthesis/genetics/*metabolism; Epithelial Cells/drug effects/metabolism; ets-Domain Protein Elk-1/biosynthesis/genetics/*metabolism; Nuclear Proteins/biosynthesis/genetics/*metabolism; RNA; Genetic; Promoter Regions; Messenger/biosynthesis/genetics

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

3862–3870

Issue

11

Volume

5

Citation

Shi Qiwen; Sutariya Vijaykumar; Bishayee Anupam; Bhatia Deepak, “Sequential activation of Elk-1/Egr-1/GADD45alpha by arsenic.,” NEOMED Bibliography Database, accessed March 29, 2024, https://neomed.omeka.net/items/show/5030.