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- Title
The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling.
- Authors
Virolle, Thierry; Adamson, Eileen D.; Baron, Veronique; Birle, Diana; Mercola, Dan; Mustelin, Tomas; de Belle, Ian
- Abstract
The PTEN tumour suppressor and pro-apoptotic 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.
- Subjects
TUMOR suppressor genes; GENETIC transcription; TRANSCRIPTION factors; IRRADIATION
- Publication
Nature Cell Biology, 2001, Vol 3, Issue 12, p1124
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb1201-1124