論文 - 詳細
| RRC ID | 65012 |
|---|---|
| 著者 | Hirano A, Nakagawa T, Yoshitane H, Oyama M, Kozuka-Hata H, Lanjakornsiripan D, Fukada Y. |
| タイトル | USP7 and TDP-43: Pleiotropic Regulation of Cryptochrome Protein Stability Paces the Oscillation of the Mammalian Circadian Clock. |
| ジャーナル | PLoS One |
| Abstract |
Mammalian Cryptochromes, CRY1 and CRY2, function as principal regulators of a transcription-translation-based negative feedback loop underlying the mammalian circadian clockwork. An F-box protein, FBXL3, promotes ubiquitination and degradation of CRYs, while FBXL21, the closest paralog of FBXL3, ubiquitinates CRYs but leads to stabilization of CRYs. Fbxl3 knockout extremely lengthened the circadian period, and deletion of Fbxl21 gene in Fbxl3-deficient mice partially rescued the period-lengthening phenotype, suggesting a key role of CRY protein stability for maintenance of the circadian periodicity. Here, we employed a proteomics strategy to explore regulators for the protein stability of CRYs. We found that ubiquitin-specific protease 7 (USP7 also known as HAUSP) associates with CRY1 and CRY2 and stabilizes CRYs through deubiquitination. Treatment with USP7-specific inhibitor or Usp7 knockdown shortened the circadian period of the cellular rhythm. We identified another CRYs-interacting protein, TAR DNA binding protein 43 (TDP-43), an RNA-binding protein. TDP-43 stabilized CRY1 and CRY2, and its knockdown also shortened the circadian period in cultured cells. The present study identified USP7 and TDP-43 as the regulators of CRY1 and CRY2, underscoring the significance of the stability control process of CRY proteins for period determination in the mammalian circadian clockwork. |
| 巻・号 | 11(4) |
| ページ | e0154263 |
| 公開日 | 2016-1-1 |
| DOI | 10.1371/journal.pone.0154263 |
| PII | PONE-D-15-40890 |
| PMID | 27123980 |
| PMC | PMC4849774 |
| MeSH | Animals Circadian Clocks / genetics* Cryptochromes / genetics* Cryptochromes / metabolism DNA-Binding Proteins / antagonists & inhibitors DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism F-Box Proteins / genetics F-Box Proteins / metabolism Feedback, Physiological Gene Expression Regulation Genes, Reporter HEK293 Cells Humans Luciferases / genetics Luciferases / metabolism Mice NIH 3T3 Cells Proteasome Endopeptidase Complex / metabolism Protein Stability Proteolysis RNA, Small Interfering / genetics RNA, Small Interfering / metabolism Signal Transduction Ubiquitin Thiolesterase / antagonists & inhibitors Ubiquitin Thiolesterase / genetics* Ubiquitin Thiolesterase / metabolism Ubiquitin-Specific Peptidase 7 Ubiquitination |
| IF | 2.74 |
| 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 | 8 |
| 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 |