論文 - 詳細
| RRC ID | 50086 |
|---|---|
| 著者 | Hayasaka N, Hirano A, Miyoshi Y, Tokuda IT, Yoshitane H, Matsuda J, Fukada Y. |
| タイトル | Salt-inducible kinase 3 regulates the mammalian circadian clock by destabilizing PER2 protein. |
| ジャーナル | Elife |
| Abstract |
Salt-inducible kinase 3 (SIK3) plays a crucial role in various aspects of metabolism. In the course of investigating metabolic defects in Sik3-deficient mice (Sik3-/-), we observed that circadian rhythmicity of the metabolisms was phase-delayed. Sik3-/- mice also exhibited other circadian abnormalities, including lengthening of the period, impaired entrainment to the light-dark cycle, phase variation in locomotor activities, and aberrant physiological rhythms. Ex vivo suprachiasmatic nucleus slices from Sik3-/- mice exhibited destabilized and desynchronized molecular rhythms among individual neurons. In cultured cells, Sik3-knockdown resulted in abnormal bioluminescence rhythms. Expression levels of PER2, a clock protein, were elevated in Sik3-knockdown cells but down-regulated in Sik3-overexpressing cells, which could be attributed to a phosphorylation-dependent decrease in PER2 protein stability. This was further confirmed by PER2 accumulation in the Sik3-/- fibroblasts and liver. Collectively, SIK3 plays key roles in circadian rhythms by facilitating phosphorylation-dependent PER2 destabilization, either directly or indirectly. |
| 巻・号 | 6 |
| 公開日 | 2017-12-11 |
| DOI | 10.7554/eLife.24779 |
| PII | 24779 |
| PMID | 29227248 |
| PMC | PMC5747517 |
| MeSH | Animals Behavior, Animal Cell Line Circadian Clocks* Gene Expression Regulation* Humans Mice Mice, Knockout Period Circadian Proteins / metabolism* Phosphorylation Protein Processing, Post-Translational* Protein Serine-Threonine Kinases / deficiency Protein Serine-Threonine Kinases / metabolism* |
| IF | 7.08 |
| 引用数 | 11 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 13 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | NIH3T3-3-4(RCB1862) |