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哺乳动物的紫外线反应:c-Jun诱导是退出p53-强加增长停止的必要条件
E Shaulian1, M Schreiber, F Piu
1Laboratory of Gene Regulation and Signal Transduction University of California, San Diego 9500 Gilman Drive 92093, La Jolla, CA, USA.
Cell
|January 4, 2001
概括
蛋白质c-Jun有助于紫外线照射过的细胞重新进入细胞循环. 然而,它通过负面调节p53和p21来促进亡,这对紫外线反应至关重要.
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:
- 哺乳动物的紫外线反应涉及到c-Jun的快速诱导,这是一个通常与mitogenic信号相关的原生基因.
- 导致生长停止的基因毒剂诱导c-Jun似乎具有悖论性.
- 了解c-Jun在紫外线反应中的作用对于理解细胞损伤和修复机制至关重要.
研究的目的:
- 阐明c-Jun在小鼠纤维细胞的紫外线反应途径中的特定功能.
- 研究c-Jun在紫外线照射后影响细胞周期进展和细胞亡的机制.
- 确定c-Jun在紫外线反应中的作用是否与其对电离辐射反应中的作用不同.
主要方法:
- 利用了缺乏c-Jun的小鼠纤维细胞和具有构成性c-Jun表达的细胞.
- 分析了紫外线照射后的细胞循环再进入和细胞亡率.
- 研究了c-Jun,p53和p21促进体之间的相互作用.
主要成果:
- 在紫外线照射的细胞中,c-Jun对于细胞循环的重新进入至关重要,但对于电离辐射的反应却不至关重要.
- 缺乏c-Jun的细胞表现出长时间的细胞周期停止和对细胞亡的抵抗.
- 构成性c-Jun表达导致细胞循环停止的失败和亡的增加.
- c-Jun负面调节p53与p21促进体结合,影响p21诱导水平.
结论:
- c-Jun在紫外线损伤后调节细胞命运决策,平衡细胞周期停止和细胞亡方面发挥着关键作用.
- 该机制涉及调节p53-p21通路,突出显示了c-Jun在线粒发育之外的复杂作用.
- 这些发现提供了对DNA损伤反应途径和潜在治疗点的见解.
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