Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination.
Hedgehog (Hh) signaling regulates multiple aspects of metazoan development and tissue homeostasis, and is constitutively active in numerous cancers. We identified Ubr3, an E3 ubiquitin ligase, as a novel, positive regulator of Hh signaling in Drosophila and vertebrates. Hh signaling regulates the Ub...
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Public Library of Science (PLoS)
2016-05-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006054&type=printable |
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| author | Tongchao Li Junkai Fan Bernardo Blanco-Sánchez Nikolaos Giagtzoglou Guang Lin Shinya Yamamoto Manish Jaiswal Kuchuan Chen Jie Zhang Wei Wei Michael T Lewis Andrew K Groves Monte Westerfield Jianhang Jia Hugo J Bellen |
| author_facet | Tongchao Li Junkai Fan Bernardo Blanco-Sánchez Nikolaos Giagtzoglou Guang Lin Shinya Yamamoto Manish Jaiswal Kuchuan Chen Jie Zhang Wei Wei Michael T Lewis Andrew K Groves Monte Westerfield Jianhang Jia Hugo J Bellen |
| author_sort | Tongchao Li |
| collection | DOAJ |
| description | Hedgehog (Hh) signaling regulates multiple aspects of metazoan development and tissue homeostasis, and is constitutively active in numerous cancers. We identified Ubr3, an E3 ubiquitin ligase, as a novel, positive regulator of Hh signaling in Drosophila and vertebrates. Hh signaling regulates the Ubr3-mediated poly-ubiquitination and degradation of Cos2, a central component of Hh signaling. In developing Drosophila eye discs, loss of ubr3 leads to a delayed differentiation of photoreceptors and a reduction in Hh signaling. In zebrafish, loss of Ubr3 causes a decrease in Shh signaling in the developing eyes, somites, and sensory neurons. However, not all tissues that require Hh signaling are affected in zebrafish. Mouse UBR3 poly-ubiquitinates Kif7, the mammalian homologue of Cos2. Finally, loss of UBR3 up-regulates Kif7 protein levels and decreases Hh signaling in cultured cells. In summary, our work identifies Ubr3 as a novel, evolutionarily conserved modulator of Hh signaling that boosts Hh in some tissues. |
| format | Article |
| id | doaj-art-4980a293e69a4e169d42d8dce10c8eec |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2016-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-4980a293e69a4e169d42d8dce10c8eec2025-08-20T02:15:40ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-05-01125e100605410.1371/journal.pgen.1006054Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination.Tongchao LiJunkai FanBernardo Blanco-SánchezNikolaos GiagtzoglouGuang LinShinya YamamotoManish JaiswalKuchuan ChenJie ZhangWei WeiMichael T LewisAndrew K GrovesMonte WesterfieldJianhang JiaHugo J BellenHedgehog (Hh) signaling regulates multiple aspects of metazoan development and tissue homeostasis, and is constitutively active in numerous cancers. We identified Ubr3, an E3 ubiquitin ligase, as a novel, positive regulator of Hh signaling in Drosophila and vertebrates. Hh signaling regulates the Ubr3-mediated poly-ubiquitination and degradation of Cos2, a central component of Hh signaling. In developing Drosophila eye discs, loss of ubr3 leads to a delayed differentiation of photoreceptors and a reduction in Hh signaling. In zebrafish, loss of Ubr3 causes a decrease in Shh signaling in the developing eyes, somites, and sensory neurons. However, not all tissues that require Hh signaling are affected in zebrafish. Mouse UBR3 poly-ubiquitinates Kif7, the mammalian homologue of Cos2. Finally, loss of UBR3 up-regulates Kif7 protein levels and decreases Hh signaling in cultured cells. In summary, our work identifies Ubr3 as a novel, evolutionarily conserved modulator of Hh signaling that boosts Hh in some tissues.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006054&type=printable |
| spellingShingle | Tongchao Li Junkai Fan Bernardo Blanco-Sánchez Nikolaos Giagtzoglou Guang Lin Shinya Yamamoto Manish Jaiswal Kuchuan Chen Jie Zhang Wei Wei Michael T Lewis Andrew K Groves Monte Westerfield Jianhang Jia Hugo J Bellen Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination. PLoS Genetics |
| title | Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination. |
| title_full | Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination. |
| title_fullStr | Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination. |
| title_full_unstemmed | Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination. |
| title_short | Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination. |
| title_sort | ubr3 a novel modulator of hh signaling affects the degradation of costal 2 and kif7 through poly ubiquitination |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006054&type=printable |
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