The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling
The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling
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DOI：
10.1038/ncb1201-1124
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发表时间：
2001-12-01
影响因子：
21.3
通讯作者：
de Belle, I
中科院分区：
文献类型：
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作者：
Virolle, T;Adamson, ED;de Belle, I
PTEN 肿瘤抑制基因 (1) 和促凋亡基因 (2) 在人类癌症中经常发生突变。我们发现，在野生型小鼠中，Egr-1 在体内照射后 PTEN 转录被上调，但 egr-1(-/-) 小鼠却没有上调。我们发现 Egr-1 特异性结合 PTEN 5' 非翻译区，该区域包含功能性 GCGGCGGCG Egr-1 结合位点。通过将细胞暴露于紫外线来诱导 Egr-1 上调 PTEN 信使 RNA 和蛋白质的表达，并导致细胞凋亡。 egr-1(-/-)细胞在照射后不能上调PTEN表达，对紫外线诱导的细胞凋亡具有抵抗力。因此，Egr-1可以直接调节PTEN，触发该凋亡途径的第一步。 Egr-1 表达缺失（常发生在人类癌症中）可能会解除 PTEN 基因的调节，并有助于某些癌细胞的辐射耐受性。
The PTEN tumour suppressor(1) and pro-apoptotic(2) 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.