论文题目: | Activation of Smurf E3 Ligase Promoted by Smoothened Regulates Hedgehog Signaling through Targeting Patched Turnover |
论文题目英文: | |
作者: | 黄守均①, #Z. Zhang①, 张春霞①, #X. Lv①, 郑秀灯, 陈振平,孙立伟, 王海龙, 朱元祥, 张静, S. Yang, #Y. Lu, 孙钦秒, 陶毅, 刘峰, #赵允*, 陈大华* |
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年: | 2013 |
卷: | 11 |
期: | 11 |
页: | e1001721 |
联系作者: | 赵允, 陈大华 |
发表期刊: | PLoS Biology |
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论文连接 | http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001721 |
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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. |
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