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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Public Library of Science (PLoS)
2009
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oai:doaj.org-article:4fd81bfa1a8b48f2a564b7a9aade4f0a2021-11-25T06:21:54ZTbx1 regulates the BMP-Smad1 pathway in a transcription independent manner.1932-620310.1371/journal.pone.0006049https://doaj.org/article/4fd81bfa1a8b48f2a564b7a9aade4f0a2009-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19557177/?tool=EBIhttps://doaj.org/toc/1932-6203Tbx1 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.F Gabriella FulcoliTuong HuynhPeter J ScamblerAntonio BaldiniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 6, p e6049 (2009) |
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Medicine R Science Q F Gabriella Fulcoli Tuong Huynh Peter J Scambler Antonio Baldini Tbx1 regulates the BMP-Smad1 pathway in a transcription independent manner. |
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 |
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 |
title |
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_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_sort |
tbx1 regulates the bmp-smad1 pathway in a transcription independent manner. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2009 |
url |
https://doaj.org/article/4fd81bfa1a8b48f2a564b7a9aade4f0a |
work_keys_str_mv |
AT fgabriellafulcoli tbx1regulatesthebmpsmad1pathwayinatranscriptionindependentmanner AT tuonghuynh tbx1regulatesthebmpsmad1pathwayinatranscriptionindependentmanner AT peterjscambler tbx1regulatesthebmpsmad1pathwayinatranscriptionindependentmanner AT antoniobaldini tbx1regulatesthebmpsmad1pathwayinatranscriptionindependentmanner |
_version_ |
1718413800987688960 |