Hedgehog-induced phosphorylation by CK1 sustains the activity of Ci/Gli activator
文献类型：期刊论文
| 作者 | Shi Q1; Li S1; Li SX1,2; Jiang A1; Chen YB3,4; Jiang J[*]1,5 |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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| 出版日期 | 2014 |
| 卷号 | 111期号:52页码:E5651-E5660 |
| 关键词 | Hedgehog CK1 Ci Gli SPOP |
| 通讯作者 | jin.jiang@UTSouthwestern.edu |
| 合作状况 | 其它 |
| 英文摘要 | Hedgehog (Hh) signaling governs many developmental processes by regulating the balance between the repressor (Ci(R)/Gli(R)) and activator (Ci(A)/Gli(A)) forms of Cubitus interruptus (Ci)/gliomaassociated oncogene homolog (Gli) transcription factors. Although much is known about how Ci(R)/Gli(R) is controlled, the regulation of Ci(A)/Gli(A) remains poorly understood. Here we demonstrate that Casein kinase 1 (CK1) sustains Hh signaling downstream of Costal2 and Suppressor of fused (Sufu) by protecting Ci(A) from premature degradation. We show that Hh stimulates Ci phosphorylation by CK1 at multiple Ser/Thr-rich degrons to inhibit its recognition by the Hh-induced MATH and BTB domain containing protein (HIB), a substrate receptor for the Cullin 3 family of E3 ubiquitin ligases. In Hh-receiving cells, reduction of CK1 activity accelerated HIB-mediated degradation of Ci(A), leading to premature loss of pathway activity. We also provide evidence that Gli(A) is regulated by CK1 in a similar fashion and that CK1 acts downstream of Sufu to promote Sonic hedgehog signaling. Taken together, our study not only reveals an unanticipated and conserved mechanism by which phosphorylation of Ci/Gli positively regulates Hh signaling but also provides the first evidence, to our knowledge, that substrate recognition by the Cullin 3 family of E3 ubiquitin ligases is negatively regulated by a kinase. |
| 收录类别 | SCI |
| 资助信息 | This work was supported by National Institutes of Health Grants GM061269 and GM067045 and Welch Founda- tion Grant I-1603 (to J.J.), and National Science Foundation of China Grants 31328017, 81322030, and 31271579 (to Y.C.). |
| 语种 | 英语 |
| WOS记录号 | WOS:000347444400010 |
| 公开日期 | 2015-02-06 |
| 源URL | [http://159.226.149.42:8088/handle/152453/8255]  |
| 专题 | 昆明动物研究所_肿瘤信号转导 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
| 作者单位 | 1.Developmental Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75235 2.Institute of Biomedical Sciences, East China Normal University, Shanghai 200062, China 3.Key Laboratory of Animal Models and Human Disease Mechanisms,Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China 4.Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China 5.Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75235 |
| 推荐引用方式 GB/T 7714 | Shi Q,Li S,Li SX,et al. Hedgehog-induced phosphorylation by CK1 sustains the activity of Ci/Gli activator[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2014,111(52):E5651-E5660. |
| APA | Shi Q,Li S,Li SX,Jiang A,Chen YB,&Jiang J[*].(2014).Hedgehog-induced phosphorylation by CK1 sustains the activity of Ci/Gli activator.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,111(52),E5651-E5660. |
| MLA | Shi Q,et al."Hedgehog-induced phosphorylation by CK1 sustains the activity of Ci/Gli activator".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 111.52(2014):E5651-E5660. |
入库方式： OAI收割
来源：昆明动物研究所
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