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首页> 外文期刊>Cell cycle >Oncogenes and the DNA damage response: Myc and E2F1 engage the ATM signaling pathway to activate p53 and induce apoptosis.
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Oncogenes and the DNA damage response: Myc and E2F1 engage the ATM signaling pathway to activate p53 and induce apoptosis.

机译：癌基因和DNA损伤反应：Myc和E2F1参与ATM信号通路来激活p53并诱导细胞凋亡。

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Activation of the ATM DNA damage response pathway is commonly observed in a variety of early-stage neoplasias. It has been proposed that this checkpoint response functions to suppress the development of cancer. A recent report from our laboratory demonstrates that ATM does indeed function to suppress tumorigenesis by responding to at least some oncogenic stresses. Transgenic expression of Myc is found to cause DNA damage in vivo and ATM is shown to respond to this damage by inducing the accumulation and phosphorylation of p53. In the absence of ATM, p53-dependent apoptosis is reduced and epithelial tumorigenesis is accelerated in Myc transgenic mice. Deregulated expression of the E2F1 transcription factor also elicits an ATM-dependent checkpoint response that activates p53 and promotes apoptosis, although the mechanism by which E2F1 and Myc stimulate ATM may differ. These findings have relevance for understanding why the ATM pathway is activated in many human cancers, what generates the selective pressure for p53 inactivation during tumorigenesis, and why AT patients and carriers are predisposed to developing cancer.
机译：ATM DNA损伤反应途径的激活通常在各种早期肿瘤中观察到。已经提出，该检查点反应起到抑制癌症发展的作用。我们实验室的最新报告表明，ATM确实可以通过至少响应某些致癌应激来抑制肿瘤发生。发现Myc的转基因表达在体内引起DNA损伤，并且ATM通过诱导p53的积累和磷酸化而对这种损伤作出反应。在没有ATM的情况下，在Myc转基因小鼠中，p53依赖性凋亡减少，上皮肿瘤发生加速。尽管E2F1和Myc刺激ATM的机制可能不同，但E2F1转录因子表达失调也会引发ATM依赖的关卡反应，从而激活p53并促进细胞凋亡。这些发现与理解为什么在许多人类癌症中激活ATM途径，在肿瘤发生过程中产生p53失活的选择性压力以及AT患者和携带者易患癌症的原因有关。

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