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ets-1 is transcriptionally up-regulated by H2O2 via an antioxidant response element
Leigh A Wilson1, Adam Gemin, Raissa Espiritu
1Juravinski Cancer Center and Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Abstract:
Expression of the transcription factor Ets-1 is increasingly associated with the progression of several human cancers. A tumor-derived factor is expected to be involved in the inappropriate up-regulation of ets-1 in tumor and surrounding cells. A link between hydrogen peroxide (H2O2) and increased Ets-1 expression has also been suggested, leading to the proposal that this reactive oxygen species (ROS) may be an important factor in directly regulating the expression of ets-1 in tumor cells. Ets-1 expression in response to H2O2 was examined in an ovarian carcinoma cell model, and the genes promoter region was analyzed in order to identify putative elements involved in redox responsiveness. The up-regulation of Ets-1 by H2O2 was confirmed in the cells tested. Luciferase assays using constructs generated to test the contribution of specific promoter elements indicated that an antioxidant response element (ARE) is primarily involved in the H2O2-mediated induction. Gel shift analysis confirmed the increased binding of an Nrf2 containing protein complex to the ets-1 ARE after H2O2 treatment. This study has delineated a key element involved in the transcriptional regulation of ets-1 under basal and induced conditions. Ets-1 has obvious deleterious effects in many cancer cells, and thus, the identification of this regulatory pathway has provided possible targets for manipulating its expression.
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Transcription
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
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Transcription
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RNA Polymerase II Accessory Proteins