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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Autores principales: F Gabriella Fulcoli, Tuong Huynh, Peter J Scambler, Antonio Baldini
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Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2009
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Acceso en línea:https://doaj.org/article/4fd81bfa1a8b48f2a564b7a9aade4f0a
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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
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AT peterjscambler tbx1regulatesthebmpsmad1pathwayinatranscriptionindependentmanner
AT antoniobaldini tbx1regulatesthebmpsmad1pathwayinatranscriptionindependentmanner
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