Oscillatory expression of the bHLH factor Hes1 regulated by a negative feedback loop
Oscillatory expression of the bHLH factor Hes1 regulated by a negative feedback loop
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DOI：
10.1126/science.1074560
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发表时间：
2002-10-25
期刊：
影响因子：
56.9
通讯作者：
Kageyama, R
中科院分区：
文献类型：
--
作者：
Hirata, H;Yoshiura, S;Kageyama, R
Notch信号分子的信使RNA（mRNA）的转录以2小时周期振荡，并且这种振荡对于协调体节分割是重要的。然而，这种振荡的分子机制仍有待确定。在这里，我们表明培养细胞的血清处理会诱导Notch效应子Hes 1（一种碱性螺旋-环-螺旋（bHLH）因子）的mRNA和蛋白质的周期性表达，周期为2小时。细胞周期是细胞自主的，依赖于Hes 1转录的负性自动调节和泛素-蛋白酶体介导的Hes 1蛋白的降解。因为Hes 1振荡可以在许多细胞类型中看到，这个时钟可以调节许多生物系统中的时间。
Transcription of messenger RNAs (mRNAs) for Notch signaling molecules oscillates with 2-hour cycles, and this oscillation is important for coordinated somite segmentation. However, the molecular mechanism of such oscillation remains to be determined. Here, we show that serum treatment of cultured cells induces cyclic expression of both mRNA and protein of the Notch effector Hes1, a basic helix-loop-helix (bHLH) factor, with 2-hour periodicity. Cycling is cell-autonomous and depends on negative autoregulation of hes1 transcription and ubiquitin-proteasome mediated degradation of Hes1 protein. Because Hes1 oscillation can be seen in many cell types, this clock may regulate timing in many biological systems.