A MODEL FOR CIRCADIAN OSCILLATIONS IN THE DROSOPHILA PERIOD PROTEIN (PER)

A MODEL FOR CIRCADIAN OSCILLATIONS IN THE DROSOPHILA PERIOD PROTEIN (PER)
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DOI:
10.1098/rspb.1995.0153
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发表时间:
1995-09-22
影响因子:
4.7
通讯作者:
GOLDBETER, A
GOLDBETER, A
中科院分区:
生物学1区
文献类型:
--
作者:
GOLDBETER, A

文献摘要

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利用理论模型研究了果蝇周期蛋白(PER)的昼夜振荡机制。考虑到最近的实验观察,生物钟的模型是基于PER的多重磷酸化和PER对周期(PER)基因转录产生的负反馈。这种最小生化模型为极限环型的昼夜节律振荡提供了分子基础。在振荡过程中,每mRNA的峰值比总PER蛋白的峰值早几个小时。这些结果支持了这样的观点,即多个PER磷酸化引入了时间延迟,其增强了负反馈产生振荡的能力。分析表明,节律只发生在一个范围内的两个临界值的PER的最大降解率。对于PER进入核的速率也得到了类似的结果。结果从PER降解速率的变化方面对PER突变体的变化期提出了初步解释。
The mechanism of circadian oscillations in the period protein (PER) in Drosophila is investigated by means of a theoretical model. Taking into account recent experimental observations, the model for the circadian clock is based on multiple phosphorylation of PER and on the negative feedback exerted by PER on the transcription of the period (per) gene. This minimal biochemical model provides a molecular basis for circadian oscillations of the limit cycle type. During oscillations, the peak in per mRNA precedes by several hours the peak in total PER protein. The results support the view that multiple PER phosphorylation introduces times delays which strengthen the capability of negative feedback to produce oscillations. The analysis shows that the rhythm only occurs in a range bounded by two critical values of the maximum rate of PER degradation. A similar result is obtained with respect to the rate of PER transport into the nucleus. The results suggest a tentative explanation for the altered period of per mutants, in terms of variations in the rate of PER degradation.