2009年9月
CKI epsilon/delta-dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- 巻
- 106
- 号
- 37
- 開始ページ
- 15744
- 終了ページ
- 15749
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1073/pnas.0908733106
- 出版者・発行元
- NATL ACAD SCIENCES
A striking feature of the circadian clock is its flexible yet robust response to various environmental conditions. To analyze the biochemical processes underlying this flexible-yet-robust characteristic, we examined the effects of 1,260 pharmacologically active compounds in mouse and human clock cell lines. Compounds that markedly (>10 s.d.) lengthened the period in both cell lines, also lengthened it in central clock tissues and peripheral clock cells. Most compounds inhibited casein kinase I epsilon (CKI epsilon) or CKI epsilon phosphorylation of the PER2 protein. Manipulation of CKI epsilon/delta dependent phosphorylation by these compounds lengthened the period of the mammalian clock from circadian ( 24 h) to circabidian ( 48 h), revealing its high sensitivity to chemical perturbation. The degradation rate of PER2, which is regulated by CKI epsilon/delta-dependent phosphorylation, was temperature-insensitive in living clock cells, yet sensitive to chemical perturbations. This temperature-insensitivity was preserved in the CKI epsilon/delta-dependent phosphorylation of a synthetic peptide in vitro. Thus, CKI epsilon/delta-dependent phosphorylation is likely a temperature-insensitive period-determining process in the mammalian circadian clock.
- リンク情報
- ID情報
-
- DOI : 10.1073/pnas.0908733106
- ISSN : 0027-8424
- PubMed ID : 19805222
- Web of Science ID : WOS:000269806600044