Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover.
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 transduce...
| Asıl Yazarlar: | , , , , , , , , , , , , , , , , |
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| Materyal Türü: | Makale |
| Dil: | English |
| Baskı/Yayın Bilgisi: |
Public Library of Science (PLoS)
2013-11-01
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| Seri Bilgileri: | PLoS Biology |
| Online Erişim: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1001721&type=printable |
| _version_ | 1826865435213037568 |
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| author | Shoujun Huang Zhao Zhang Chunxia Zhang Xiangdong Lv Xiudeng Zheng Zhenping Chen Liwei Sun Hailong Wang Yuanxiang Zhu Jing Zhang Shuyan Yang Yi Lu Qinmiao Sun Yi Tao Feng Liu Yun Zhao Dahua Chen |
| author_facet | Shoujun Huang Zhao Zhang Chunxia Zhang Xiangdong Lv Xiudeng Zheng Zhenping Chen Liwei Sun Hailong Wang Yuanxiang Zhu Jing Zhang Shuyan Yang Yi Lu Qinmiao Sun Yi Tao Feng Liu Yun Zhao Dahua Chen |
| author_sort | Shoujun Huang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T03:40:04Z |
| format | Article |
| id | doaj.art-dcdd02c7a6ec4e928b97e59af0dcac7a |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2025-02-16T21:40:57Z |
| publishDate | 2013-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-dcdd02c7a6ec4e928b97e59af0dcac7a2025-01-17T05:30:44ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852013-11-011111e100172110.1371/journal.pbio.1001721Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover.Shoujun HuangZhao ZhangChunxia ZhangXiangdong LvXiudeng ZhengZhenping ChenLiwei SunHailong WangYuanxiang ZhuJing ZhangShuyan YangYi LuQinmiao SunYi TaoFeng LiuYun ZhaoDahua ChenHedgehog 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.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1001721&type=printable |
| spellingShingle | Shoujun Huang Zhao Zhang Chunxia Zhang Xiangdong Lv Xiudeng Zheng Zhenping Chen Liwei Sun Hailong Wang Yuanxiang Zhu Jing Zhang Shuyan Yang Yi Lu Qinmiao Sun Yi Tao Feng Liu Yun Zhao Dahua Chen Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover. PLoS Biology |
| title | Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover. |
| title_full | Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover. |
| title_fullStr | Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover. |
| title_full_unstemmed | Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover. |
| title_short | Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover. |
| title_sort | activation of smurf e3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1001721&type=printable |
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