Asher Gad, Schibler Ueli
Department of Molecular Biology, Sciences III, University of Geneva, 30 Quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland.
Trends Cell Biol. 2006 Nov;16(11):547-9. doi: 10.1016/j.tcb.2006.09.005. Epub 2006 Sep 25.
Mammalian physiology is governed by a complex circadian timing system that involves interacting positive and negative transcriptional feedback loops. A key role in this feedback loop was attributed to the PAS domain helix-loop-helix protein CLOCK, on the basis of a dominant-negative mutation in this transcription factor. However, recent experiments by Reppert and coworkers with Clock knockout mice suggest that CLOCK is dispensable for rhythmic gene expression and behavior, presumably because other proteins can substitute for CLOCK in these animals.
哺乳动物的生理机能受一个复杂的昼夜节律计时系统调控,该系统涉及相互作用的正转录反馈环和负转录反馈环。基于该转录因子中的一个显性负性突变,在这个反馈环中的关键作用被归因于PAS结构域螺旋-环-螺旋蛋白CLOCK。然而,雷珀特及其同事最近对Clock基因敲除小鼠进行的实验表明,CLOCK对于节律性基因表达和行为并非必不可少,大概是因为在这些动物中其他蛋白质可以替代CLOCK。