The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling
- 6 November 2001
- journal article
- research article
- Published by Springer Nature in Nature Cell Biology
- Vol. 3 (12), 1124-1128
- https://doi.org/10.1038/ncb1201-1124
Abstract
The PTEN tumour suppressor1 and pro-apoptotic2 gene is frequently mutated in human cancers. We show that PTEN transcription is upregulated by Egr-1 after irradiation in wild-type, but not egr-1−/−, mice in vivo. We found that Egr-1 specifically binds to the PTEN 5′ untranslated region, which contains a functional GCGGCGGCG Egr-1-binding site. Inducing Egr-1 by exposing cells to ultraviolet light upregulates expression of PTEN messenger RNA and protein, and leads to apoptosis. egr-1−/− cells, which cannot upregulate PTEN expression after irradiation, are resistant to ultraviolet-light-induced apoptosis. Therefore, Egr-1 can directly regulate PTEN, triggering the initial step in this apoptotic pathway. Loss of Egr-1 expression, which often occurs in human cancers, could deregulate the PTEN gene and contribute to the radiation resistance of some cancer cells.Keywords
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