PNAS:昼夜节律的分子机制

2018-03-20 海北 MedSci原创

机体行为和生理的节律是由生物钟产生的,生物钟是由节律基因和其编码的蛋白质形成转录/翻译反馈环(TTFL)形成的。

机体行为和生理的节律是由生物钟产生的,生物钟是由节律基因和其编码的蛋白质形成转录/翻译反馈环(TTFL)形成的。生物钟是一个自持振荡器,能够灵活地响应各种时间线索,与环境的24小时周期同步。然而至今为止,将细胞应激传递给昼夜发条的关键分子还是未知的。

最近,来自东京大学的研究人员发现凋亡信号调节激酶(ASK),MAPKKK家族的成员之一,能够作为培养细胞响应培养基渗透变化的昼夜节律的重要介质。能够有节律地响应细胞内氧化还原状态的变化证明了ASK信号的生理影响。有趣的是,TTFL能够驱动Ask基因的节律表达,表明ASK介导的TTFL与细胞内氧化还原的关联。

在行为分析中,Ask1Ask2Ask3三重敲除的小鼠表现出昼夜节律和活动节律对光照的反应受损。

基于LC-MS / MS的蛋白质组学分析鉴定出一系列ASK依赖性的和渗透压应答的磷酸化蛋白质,其中分子发条的关键组分CLOCK在羧基末端区域的Thr843Ser845处存在磷酸化。

这些发现揭示了ASK依赖性应激反应是昼夜节律的机制之一。


原始出处:

Kiyomichi Imamura et al. ASK family kinases mediate cellular stress and redox signaling to circadian clockProceedings of the National Academy of Sciences, 2018; 201719298 DOI: 10.1073/pnas.1719298115


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    2019-01-25 drwjr
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    2018-03-21 小小小蹄子

    学习了.我们刚拿到一个昼夜节律和放射敏感性的基金!

    0

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    2018-03-20 183****7028

    学习

    0

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    2018-03-20 183****7028

    学习

    0

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    2018-03-20 sunfeifeiyang

    0

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    2018-03-20 121e6640m66暂无昵称

    学习

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