PP2A/B56delta酸酶在调节来自Cdc25的14-3-3释放中的作用,以控制线粒分裂
Seth S Margolis1, Jennifer A Perry, Craig M Forester
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Cell
|November 18, 2006
概括
DNA损伤检查点通过控制线粒激活剂Cdc25来调节细胞分裂. 这项研究揭示了PP2A/B56delta酸酶和14-3-3蛋白相互作用如何激活Cdc25以促进细胞周期进展.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 响应DNA检查点对于防止DNA损伤后细胞循环进展至关重要.
- 线粒激活剂Cdc25通过抑制酸化和14-3-3蛋白结合来调节.
- 线粒体进入需要去除14-3-3蛋白和Cdc25在Ser287.7上的脱化.
研究的目的:
- 研究PP2A/B56delta酸酶在Cdc25.的DNA响应检查点控制中的作用.
- 阐明Cdc25被激活以促进线粒体进入的机制.
主要方法:
- 研究了通过PP2A/B56delta.对Cdc25的脱化.
- 分析了T138酸化在14-3-3结合Cdc25.5中的作用.
- 使用中间丝蛋白检查了14-3-3"水槽"的形成.
主要成果:
- 响应DNA检查点激活PP2A/B56delta,在T138处去化Cdc25,与Ser287.7不同.
- T138酸化是必要的,但不足以使14-3-3从Cdc25释放出来.
- 由中间丝蛋白形成的14-3-3"下水槽"和降低的Cdc25-14-3-3亲和力有助于Cdc25的激活.
结论:
- PP2A/B56delta是调节Cdc25的DNA反应检查点的一个关键效应因子.
- 一个涉及14-3-3"沉没"的新机制和改变的蛋白质亲和力控制了Cdc25激活和线粒体进入.
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