A role for the proteasome in the light response of the timeless clock protein
A role for the proteasome in the light response of the timeless clock protein
复制标题
DOI：
10.1126/science.285.5434.1737
复制
发表时间：
1999-09-10
期刊：
影响因子：
56.9
通讯作者：
Sehgal, A
中科院分区：
文献类型：
--
作者：
Naidoo, N;Song, W;Sehgal, A
周期蛋白（PER）和无时间蛋白（TIM）的周期性表达是果蝇分子昼夜节律反馈环的关键。光对生物钟的诱导是通过TIM水平的降低来介导的。为了阐明这一过程的机制，在体外试验中用候选蛋白水解途径的抑制剂测试了光对TIM调节的敏感性。这些数据表明，TIM是通过泛素-蛋白酶体机制降解的。此外，在三龄幼虫的培养物中，TIM降解被蛋白酶体活性抑制剂特异性阻断。降解之前出现酪氨酸磷酸化。最后，TIM在培养的细胞中响应于光而被泛素化。
The cyclic expression of the period (PER) and timeless (TIM) proteins is critical for the molecular circadian feedback Loop in Drosophila. The entrainment by Light of the circadian clock is mediated by a reduction in TIM Levels. To elucidate the mechanism of this process, the sensitivity of TIM regulation by Light was tested in an in vitro assay with inhibitors of candidate proteolytic pathways. The data suggested that TIM is degraded through a ubiquitin-proteasome mechanism. In addition, in cultures from third-instar Larvae, TIM degradation was blocked specifically by inhibitors of proteasome activity. Degradation appeared to be preceded by tyrosine phosphorylation. Finally, TIM was ubiquitinated in response to Light in cultured cells.