A role for glycogen synthase kinase-3beta in the mammalian circadian clock
Autor: | Norio Ishida, Toshihiro Akaike, Chisato Iitaka, Koyomi Miyazaki |
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Rok vydání: | 2005 |
Předmět: |
Timeless
Period (gene) Circadian clock Active Transport Cell Nucleus Cell Cycle Proteins macromolecular substances Biology Biochemistry Glycogen Synthase Kinase 3 Mice Basic Helix-Loop-Helix Transcription Factors Animals Circadian rhythm RNA Messenger Phosphorylation Glycogen synthase Molecular Biology Mice Inbred ICR Binding Sites Glycogen Synthase Kinase 3 beta Suprachiasmatic nucleus ARNTL Transcription Factors Nuclear Proteins Cell Biology Period Circadian Proteins Circadian Rhythm PER2 CLOCK biology.protein NIH 3T3 Cells Transcription Factors |
Zdroj: | The Journal of biological chemistry. 280(33) |
ISSN: | 0021-9258 |
Popis: | The Drosophila shaggy gene product is a mammalian glycogen synthase kinase-3beta (GSK-3beta) homologue that contributes to the circadian clock of the Drosophila through TIMELESS phosphorylation, and it regulates nuclear translocation of the PERIOD/TIMELESS heterodimer. We found that mammalian GSK-3beta is expressed in the suprachiasmatic nucleus and liver of mice and that GSK-3beta phosphorylation exhibits robust circadian oscillation. Rhythmic GSK-3beta phosphorylation is also observed in serum-shocked NIH3T3 cells. Exposing serum-shocked NIH3T3 cells to lithium chloride, a specific inhibitor of GSK-3beta, increases GSK-3beta phosphorylation and delays the phase of rhythmic clock gene expression. On the other hand, GSK-3beta overexpression advances the phase of clock gene expression. We also found that GSK-3beta interacts with PERIOD2 (PER2) in vitro and in vivo. Recombinant GSK-3beta can phosphorylate PER2 in vitro. GSK-3beta promotes the nuclear translocation of PER2 in COS1 cells. The present data suggest that GSK-3beta plays important roles in mammalian circadian clock. |
Databáze: | OpenAIRE |
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