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Text
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URL Address
<a href="http://doi.org/10.18632/oncotarget.1995" target="_blank" rel="noreferrer noopener">http://doi.org/10.18632/oncotarget.1995</a>
Pages
3862–3870
Issue
11
Volume
5
Dublin Core
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Title
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Sequential activation of Elk-1/Egr-1/GADD45alpha by arsenic.
Publisher
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Oncotarget
Date
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2014
2014-06
Subject
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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
Creator
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Shi Qiwen; Sutariya Vijaykumar; Bishayee Anupam; Bhatia Deepak
Description
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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.
Identifier
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<a href="http://doi.org/10.18632/oncotarget.1995" target="_blank" rel="noreferrer noopener">10.18632/oncotarget.1995</a>
Rights
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2014
Arsenic/*pharmacology
Bhatia Deepak
Bishayee Anupam
Bronchi/cytology/drug effects/metabolism
Cell Cycle Proteins/biosynthesis/genetics/*metabolism
Cell Line
Early Growth Response Protein 1/biosynthesis/genetics/*metabolism
Epithelial Cells/drug effects/metabolism
ets-Domain Protein Elk-1/biosynthesis/genetics/*metabolism
Genetic
Humans
MAP Kinase Signaling System
Messenger/biosynthesis/genetics
Nuclear Proteins/biosynthesis/genetics/*metabolism
Oncotarget
Promoter Regions
Proto-Oncogene Proteins c-akt/metabolism
RNA
Shi Qiwen
Sutariya Vijaykumar