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.
| Original language | English |
|---|---|
| Article number | e6049 |
| Journal | PLoS One |
| Volume | 4 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 25 2009 |
Fingerprint
ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Tbx1 regulates the BMP-smad1 pathway in a transcription independent manner. / Fulcoli, F. Gabriella; Huynh, Tuong; Scambler, Peter J.; Baldini, Antonio.
In: PLoS One, Vol. 4, No. 6, e6049, 25.06.2009.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tbx1 regulates the BMP-smad1 pathway in a transcription independent manner
AU - Fulcoli, F. Gabriella
AU - Huynh, Tuong
AU - Scambler, Peter J.
AU - Baldini, Antonio
PY - 2009/6/25
Y1 - 2009/6/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=67649503019&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67649503019&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0006049
DO - 10.1371/journal.pone.0006049
M3 - Article
VL - 4
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 6
M1 - e6049
ER -