title: Sequential activation of Elk-1/Egr-1/GADD45α by arsenic.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Northeast Ohio Medical University (NEOMED), Rootstown, Ohio, USA; School of Biomedical Sciences, Kent State University, Kent, Ohio, USA.
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Shi
authors.forename: Vijaykumar
authors.initials: V
authors.lastname: Sutariya
authors.forename: Anupam
authors.initials: A
authors.lastname: Bishayee
authors.affiliation: Department of Pharmaceutical Sciences, Northeast Ohio Medical University (NEOMED), Rootstown, Ohio, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Bhatia
mesh_terms: D001151:Arsenic / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D050807:ets-Domain Protein Elk-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000097642:GADD45 Proteins
chemical_list: D001151:Arsenic; D018797:Cell Cycle Proteins; D051766:Early Growth Response Protein 1; D009687:Nuclear Proteins; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D050807:ets-Domain Protein Elk-1; C497325:EGR1 protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins