小鼠纤维细胞对基因毒性压力的三个不同的信号响应
Z G Liu1, R Baskaran, E T Lea-Chou
1Department of Pharmacology, Program in Biomedical Science, School of Medicine, University of California, San Diego 92093, USA.
Nature
|November 21, 1996
概括
蛋白质p53是基因毒性压力的通用传感器,对所有测试的DNA损伤剂作出反应. 然而,其他压力激活的蛋白质,如c-Abl和Jun激酶 (JNKs) 被特定的基因毒素激活,表明不同的细胞反应.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 基因毒性压力会激活细胞信号通路以进行保护或细胞死亡.
- p53的诱导发生在核中,而AP-1和NF-kappaB通过紫外线辐射的激活涉及膜信号.
- 激酶 (JNKs) 和c-Abl氨酸激酶与对基因毒性压力的反应有关.
研究的目的:
- 为了研究p53,JNK和c-Abl激活之间的关系,通过各种DNA损伤剂.
- 为了确定哪些信号蛋白在基因毒性压力下被普遍激活.
主要方法:
- 在暴露于不同基因毒剂的小鼠纤维细胞中比较p53,JNK和c-Abl激活.
- 在c-Abl-null和c-Src-null细胞中JNK激活的分析.
- 对c-Abl激活的细胞周期分析.
主要成果:
- 所有测试的基因毒性刺激都诱导了p53.
- c-Abl被大多数刺激激活,但不包括紫外线照射.
- 紫外线和甲基甲硫酸盐强烈刺激了JNK,后者的激活独立于c-Abl,但依赖于c-Src.
- c-Abl激活发生在S阶段,不会影响细胞增殖.
结论:
- 基因毒性压力信号通过多条独立的途径传播.
- 在研究的蛋白质中,p53是唯一的基因毒性压力的通用传感器.
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