Unknown

Dataset Information

0

Tbx1 regulates the BMP-Smad1 pathway in a transcription independent manner.


ABSTRACT: 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.

SUBMITTER: Fulcoli FG 

PROVIDER: S-EPMC2698216 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Tbx1 regulates the BMP-Smad1 pathway in a transcription independent manner.

Fulcoli F Gabriella FG   Huynh Tuong T   Scambler Peter J PJ   Baldini Antonio A  

PloS one 20090625 6


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  ...[more]

Similar Datasets

| S-EPMC7175193 | biostudies-literature
2024-05-22 | PXD035207 | Pride
| S-EPMC4068743 | biostudies-literature
| S-SCDT-10_1038-S44319-023-00046-W | biostudies-other
| S-EPMC1567677 | biostudies-literature
| S-EPMC2200633 | biostudies-literature
| S-EPMC3585476 | biostudies-other
| S-EPMC9763856 | biostudies-literature
| S-EPMC3340481 | biostudies-literature
| S-EPMC8465227 | biostudies-literature