Qing-Jun Meng, Elizabeth S Maywood, David A Bechtold, Wei-Qun Lu, Jian Li, Julie E Gibbs, Sandrine M Dupré, Johanna E Chesham, Francis Rajamohan, John Knafels, Blossom Sneed, Laura E Zawadzke, Jeffrey F Ohren, Kevin M Walton, Travis T Wager, Michael H Hastings, Andrew S I Loudon
Circadian pacemaking requires the orderly synthesis, posttranslational modification, and degradation of clock proteins. In mammals, mutations in casein kinase 1 (CK1) epsilon or delta can alter the circadian period, but the particular functions of the WT isoforms within the pacemaker remain unclear. We selectively targeted WT CK1epsilon and CK1delta using pharmacological inhibitors (PF-4800567 and PF-670462, respectively) alongside genetic knockout and knockdown to reveal that CK1 activity is essential to molecular pacemaking...
August 24, 2010: Proceedings of the National Academy of Sciences of the United States of America