期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：34
页码：15240-15245
DOI：10.1073/pnas.1005101107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Circadian pacemaking requires the orderly synthesis, posttranslational modification, and degradation of clock proteins. In mammals, mutations in casein kinase 1 (CK1) {varepsilon} or {delta} can alter the circadian period, but the particular functions of the WT isoforms within the pacemaker remain unclear. We selectively targeted WT CK1{varepsilon} and CK1{delta} using pharmacological inhibitors (PF-4800567 and PF-670462, respectively) alongside genetic knockout and knockdown to reveal that CK1 activity is essential to molecular pacemaking. Moreover, CK1{delta} is the principal regulator of the clock period: pharmacological inhibition of CK1{delta
关键词：circadian clock ; suprachiasmatic nucleus ; period protein ; Tau mutation ; pacemaking
