Activation of Smurf E3 Ligase Promoted by Smoothened Regulates Hedgehog Signaling through Targeting Patched Turnover
文献类型：期刊论文
| 作者 | Huang, SJ; Zhang, Z; Zhang, CX; Lv, XD; Zheng, XD; Chen, ZP; Sun, LW; Wang, HL; Zhu, YX; Zhang, J |
| 刊名 | PLOS BIOLOGY
 |
| 出版日期 | 2013 |
| 卷号 | 11期号:11页码:e1001721-e1001721 |
| 通讯作者 | Huang, SJ (reprint author), Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing, Peoples R China.,yunzhao@sibs.ac.cn ; chendh@ioz.ac.cn |
| 英文摘要 | Hedgehog signaling plays conserved roles in controlling embryonic development; its dysregulation has been implicated in many human diseases including cancers. Hedgehog signaling has an unusual reception system consisting of two transmembrane proteins, Patched receptor and Smoothened signal transducer. Although activation of Smoothened and its downstream signal transduction have been intensively studied, less is known about how Patched receptor is regulated, and particularly how this regulation contributes to appropriate Hedgehog signal transduction. Here we identified a novel role of Smurf E3 ligase in regulating Hedgehog signaling by controlling Patched ubiquitination and turnover. Moreover, we showed that Smurf-mediated Patched ubiquitination depends on Smo activity in wing discs. Mechanistically, we found that Smo interacts with Smurf and promotes it to mediate Patched ubiquitination by targeting the K1261 site in Ptc. The further mathematic modeling analysis reveals that a bidirectional control of activation of Smo involving Smurf and Patched is important for signal-receiving cells to precisely interpret external signals, thereby maintaining Hedgehog signaling reliability. Finally, our data revealed an evolutionarily conserved role of Smurf proteins in controlling Hh signaling by targeting Ptc during development. |
| 学科主题 | Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics |
| 类目[WOS] | Biochemistry & Molecular Biology ; Biology |
| 关键词[WOS] | GERMLINE STEM-CELLS ; PROTEIN-KINASE-A ; MORPHOGEN GRADIENT ; UBIQUITIN LIGASES ; MEMBRANE-PROTEIN ; FEEDBACK LOOP ; GENE ENCODES ; HECT FAMILY ; DROSOPHILA ; RECEPTOR |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000330352200023 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/440]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Huang, SJ,Zhang, Z,Zhang, CX,et al. Activation of Smurf E3 Ligase Promoted by Smoothened Regulates Hedgehog Signaling through Targeting Patched Turnover[J]. PLOS BIOLOGY,2013,11(11):e1001721-e1001721. |
| APA | Huang, SJ.,Zhang, Z.,Zhang, CX.,Lv, XD.,Zheng, XD.,...&Chen, DH.(2013).Activation of Smurf E3 Ligase Promoted by Smoothened Regulates Hedgehog Signaling through Targeting Patched Turnover.PLOS BIOLOGY,11(11),e1001721-e1001721. |
| MLA | Huang, SJ,et al."Activation of Smurf E3 Ligase Promoted by Smoothened Regulates Hedgehog Signaling through Targeting Patched Turnover".PLOS BIOLOGY 11.11(2013):e1001721-e1001721. |
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