Tbx1 regulates the BMP-Smad1 pathway in a transcription independent manner.
Tbx1 is a T-box transcription factor implicated in DiGeorge syndrome. The molecular function of Tbx1 is unclear although it can transactivate reporters with T-box binding elements. We discovered that Tbx1 binds Smad1 and suppresses the Bmp4/Smad1 signaling. Tbx1 interferes with Smad1 to Smad4 bindin...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-06-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0006049&type=printable |
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| _version_ | 1850108083669303296 |
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| author | F Gabriella Fulcoli Tuong Huynh Peter J Scambler Antonio Baldini |
| author_facet | F Gabriella Fulcoli Tuong Huynh Peter J Scambler Antonio Baldini |
| author_sort | F Gabriella Fulcoli |
| collection | DOAJ |
| description | Tbx1 is a T-box transcription factor implicated in DiGeorge syndrome. The molecular function of Tbx1 is unclear although it can transactivate reporters with T-box binding elements. We discovered that Tbx1 binds Smad1 and suppresses the Bmp4/Smad1 signaling. Tbx1 interferes with Smad1 to Smad4 binding, and a mutation of Tbx1 that abolishes transactivation, does not affect Smad1 binding nor does affect the ability to suppress Smad1 activity. In addition, a disease-associated mutation of TBX1 that does not prevent transactivation, prevents the TBX1-SMAD1 interaction. Expression of Tbx1 in transgenic mice generates phenotypes similar to those associated with loss of a Bmp receptor. One phenotype could be rescued by transgenic Smad1 expression. Our data indicate that Tbx1 interferes with Bmp/Smad1 signaling and provide strong evidence that a T-box transcription factor has functions unrelated to transactivation. |
| format | Article |
| id | doaj-art-4fd81bfa1a8b48f2a564b7a9aade4f0a |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2009-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-4fd81bfa1a8b48f2a564b7a9aade4f0a2025-08-20T02:38:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-06-0146e604910.1371/journal.pone.0006049Tbx1 regulates the BMP-Smad1 pathway in a transcription independent manner.F Gabriella FulcoliTuong HuynhPeter J ScamblerAntonio BaldiniTbx1 is a T-box transcription factor implicated in DiGeorge syndrome. The molecular function of Tbx1 is unclear although it can transactivate reporters with T-box binding elements. We discovered that Tbx1 binds Smad1 and suppresses the Bmp4/Smad1 signaling. Tbx1 interferes with Smad1 to Smad4 binding, and a mutation of Tbx1 that abolishes transactivation, does not affect Smad1 binding nor does affect the ability to suppress Smad1 activity. In addition, a disease-associated mutation of TBX1 that does not prevent transactivation, prevents the TBX1-SMAD1 interaction. Expression of Tbx1 in transgenic mice generates phenotypes similar to those associated with loss of a Bmp receptor. One phenotype could be rescued by transgenic Smad1 expression. Our data indicate that Tbx1 interferes with Bmp/Smad1 signaling and provide strong evidence that a T-box transcription factor has functions unrelated to transactivation.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0006049&type=printable |
| spellingShingle | F Gabriella Fulcoli Tuong Huynh Peter J Scambler Antonio Baldini Tbx1 regulates the BMP-Smad1 pathway in a transcription independent manner. PLoS ONE |
| title | Tbx1 regulates the BMP-Smad1 pathway in a transcription independent manner. |
| title_full | Tbx1 regulates the BMP-Smad1 pathway in a transcription independent manner. |
| title_fullStr | Tbx1 regulates the BMP-Smad1 pathway in a transcription independent manner. |
| title_full_unstemmed | Tbx1 regulates the BMP-Smad1 pathway in a transcription independent manner. |
| title_short | Tbx1 regulates the BMP-Smad1 pathway in a transcription independent manner. |
| title_sort | tbx1 regulates the bmp smad1 pathway in a transcription independent manner |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0006049&type=printable |
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