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由负反馈自动调节和泛素化引起的Hes7振荡。

Oscillations of Hes7 caused by negative autoregulation and ubiquitination.

作者信息

Zeiser S, Rivera O, Kuttler C, Hense B, Lasser R, Winkler G

机构信息

GSF, National Research Centre for Environment and Health, Institute of Biomathematics and Biometry, Ingolstädter Landstrasse 1, 85764 Oberschleissheim, Germany.

出版信息

Comput Biol Chem. 2008 Feb;32(1):47-51. doi: 10.1016/j.compbiolchem.2007.09.004. Epub 2007 Sep 18.

Abstract

Loss of Hes7 function leads to irregular somite formation demonstrating that Hes7 is a crucial component of the segmentation clock during somitogenesis. Experiments revealed that not only the repressor functionality but also the half-life of the protein is crucial for oscillatory expression of Hes7 and regular somite formation. Numerical integration of a delay equation system supported this finding. However, in a recent paper it was shown that the number of binding sites is also decisive for damped or undamped oscillations. It was shown that for more than one binding site the Hill coefficient increases. This leads to a completely different behavior. The oscillations are undamped and thus the mathematical model can no longer explain the results observed in the experiments. In this paper we propose a more sophisticated model for the Hes7 oscillator. Since Hes7 is degraded by the ubiquitin-proteasome pathway we include Michaelis-Menten kinetics for the ubiquitination of Hes7. We identify the Michaelis-Menten constant as an additional model parameter for oscillatory behavior. By increasing the Michaelis-Menten constant we found damped oscillations even if the Hill coefficient is increased.

摘要

Hes7功能的丧失会导致体节形成不规则,这表明Hes7是体节发生过程中分割时钟的关键组成部分。实验表明,不仅阻遏物功能,而且蛋白质的半衰期对于Hes7的振荡表达和规则的体节形成都至关重要。延迟方程系统的数值积分支持了这一发现。然而,在最近的一篇论文中表明,结合位点的数量对于阻尼或无阻尼振荡也起决定性作用。结果表明,对于不止一个结合位点,希尔系数会增加。这会导致完全不同的行为。振荡是无阻尼的,因此数学模型不再能解释实验中观察到的结果。在本文中,我们为Hes7振荡器提出了一个更复杂的模型。由于Hes7通过泛素-蛋白酶体途径降解,我们纳入了Hes7泛素化的米氏动力学。我们将米氏常数确定为振荡行为的一个额外模型参数。通过增加米氏常数,我们发现即使希尔系数增加,振荡也是阻尼的。

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