使用p53和GADD45的哺乳动物细胞循环检查点通路在阿塔克西亚 - 泰朗吉克塔西亚中是有缺陷的
M B Kastan1, Q Zhan, W S el-Deiry
1Johns Hopkins Oncology Center, Baltimore, Maryland 21287.
Cell
|November 23, 1992
概括
破坏细胞循环检查点,如涉及p53和GADD45的检查点,会损害DNA损伤反应. 这条通路对于细胞生存和预防突变至关重要,缺陷可能导致癌症.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 细胞周期检查点对于在DNA受损后保持基因组稳定至关重要.
- 电离辐射 (IR) 可以触发细胞循环停止,从而允许DNA修复.
- 在DNA损伤反应途径中的缺陷与癌症倾向和放射敏感性有关.
研究的目的:
- 调查p53和GADD45在G1细胞周期检查点对IR反应中的作用.
- 为了确定DNA损伤诱导的信号传导途径的关键组件.
- 探索路径异常与癌症发展之间的联系.
主要方法:
- 在小鼠纤维细胞中破坏野生类型的p53等位基因.
- 分析了来自阿塔克西亚 - 泰朗基阿克塔西亚 (AT) 患者的细胞中的p53蛋白水平.
- 评估IR诱导的GADD45基因表达.
- 电泳运动转移试验用于研究p53-DNA结合.
主要成果:
- 干扰p53消除了在小鼠纤维细胞中IR诱导的G1检查点.
- 亚特细胞显示出缺陷的IR诱导的p53积累和GADD45诱导.
- 野生类型的p53直接与GADD45基因促进体中的保存元素结合.
- 在被辐射的细胞中发现了一种与GADD45结合的p53依赖性核因子.
结论:
- 一个涉及AT基因 (s),p53和GADD45的信号转导途径在DNA损伤后调解细胞循环停止.
- 这个通路的异常有助于辐射敏感性和可能的癌症发展.
- 在IR之后,p53在调节GADD45表达和细胞周期控制方面发挥着关键作用.
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