Regulation of hedgehog signaling by Myc-interacting zinc finger protein 1, Miz1.
Smoothened (Smo) mediated Hedgehog (Hh) signaling plays an essential role in regulating embryonic development and postnatal tissue homeostasis. Aberrant activation of the Hh pathway contributes to the formation and progression of various cancers. In vertebrates, however, key regulatory mechanisms re...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3643979?pdf=render |
| _version_ | 1818675913567502336 |
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| author | Jiuyi Lu Minyong Chen Xiu-Rong Ren Jiangbo Wang H Kim Lyerly Larry Barak Wei Chen |
| author_facet | Jiuyi Lu Minyong Chen Xiu-Rong Ren Jiangbo Wang H Kim Lyerly Larry Barak Wei Chen |
| author_sort | Jiuyi Lu |
| collection | DOAJ |
| description | Smoothened (Smo) mediated Hedgehog (Hh) signaling plays an essential role in regulating embryonic development and postnatal tissue homeostasis. Aberrant activation of the Hh pathway contributes to the formation and progression of various cancers. In vertebrates, however, key regulatory mechanisms responsible for transducing signals from Smo to the nucleus remain to be delineated. Here, we report the identification of Myc-interacting Zinc finger protein 1 (Miz1) as a Smo and Gli2 binding protein that positively regulates Hh signaling. Overexpression of Miz1 increases Gli luciferase reporter activity, whereas knockdown of endogenous Miz1 has the opposite effect. Activation of Smo induces translocation of Miz1 to the primary cilia together with Smo and Gli2. Furthermore, Miz1 is localized to the nucleus upon Hh activation in a Smo-dependent manner, and loss of Miz1 prevents the nuclear translocation of Gli2. More importantly, silencing Miz1 expression inhibits cell proliferation in vitro and the growth of Hh-driven medulloblastoma tumors allografted in SCID mice. Taken together, these results identify Miz1 as a novel regulator in the Hh pathway that plays an important role in mediating Smo-dependent oncogenic signaling. |
| first_indexed | 2024-12-17T08:35:08Z |
| format | Article |
| id | doaj.art-5ad50d91188746c7bfc0d1cce7ee1328 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T08:35:08Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5ad50d91188746c7bfc0d1cce7ee13282022-12-21T21:56:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6335310.1371/journal.pone.0063353Regulation of hedgehog signaling by Myc-interacting zinc finger protein 1, Miz1.Jiuyi LuMinyong ChenXiu-Rong RenJiangbo WangH Kim LyerlyLarry BarakWei ChenSmoothened (Smo) mediated Hedgehog (Hh) signaling plays an essential role in regulating embryonic development and postnatal tissue homeostasis. Aberrant activation of the Hh pathway contributes to the formation and progression of various cancers. In vertebrates, however, key regulatory mechanisms responsible for transducing signals from Smo to the nucleus remain to be delineated. Here, we report the identification of Myc-interacting Zinc finger protein 1 (Miz1) as a Smo and Gli2 binding protein that positively regulates Hh signaling. Overexpression of Miz1 increases Gli luciferase reporter activity, whereas knockdown of endogenous Miz1 has the opposite effect. Activation of Smo induces translocation of Miz1 to the primary cilia together with Smo and Gli2. Furthermore, Miz1 is localized to the nucleus upon Hh activation in a Smo-dependent manner, and loss of Miz1 prevents the nuclear translocation of Gli2. More importantly, silencing Miz1 expression inhibits cell proliferation in vitro and the growth of Hh-driven medulloblastoma tumors allografted in SCID mice. Taken together, these results identify Miz1 as a novel regulator in the Hh pathway that plays an important role in mediating Smo-dependent oncogenic signaling.http://europepmc.org/articles/PMC3643979?pdf=render |
| spellingShingle | Jiuyi Lu Minyong Chen Xiu-Rong Ren Jiangbo Wang H Kim Lyerly Larry Barak Wei Chen Regulation of hedgehog signaling by Myc-interacting zinc finger protein 1, Miz1. PLoS ONE |
| title | Regulation of hedgehog signaling by Myc-interacting zinc finger protein 1, Miz1. |
| title_full | Regulation of hedgehog signaling by Myc-interacting zinc finger protein 1, Miz1. |
| title_fullStr | Regulation of hedgehog signaling by Myc-interacting zinc finger protein 1, Miz1. |
| title_full_unstemmed | Regulation of hedgehog signaling by Myc-interacting zinc finger protein 1, Miz1. |
| title_short | Regulation of hedgehog signaling by Myc-interacting zinc finger protein 1, Miz1. |
| title_sort | regulation of hedgehog signaling by myc interacting zinc finger protein 1 miz1 |
| url | http://europepmc.org/articles/PMC3643979?pdf=render |
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