Tbx1 regulates the BMP-smad1 pathway in a transcription independent manner

F. Gabriella Fulcoli, Tuong Huynh, Peter J. Scambler, Antonio Baldini

Research output: Contribution to journalArticle

64 Citations (Scopus)

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 languageEnglish
Article numbere6049
JournalPLoS One
Volume4
Issue number6
DOIs
Publication statusPublished - Jun 25 2009

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transcriptional activation
Transcription
Transcriptional Activation
Transcription Factors
transcription (genetics)
transcription factors
DiGeorge Syndrome
Phenotype
mutation
phenotype
gene expression
Mutation
Transgenic Mice
receptors
mice

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Fulcoli, F. G., Huynh, T., Scambler, P. J., & Baldini, A. (2009). Tbx1 regulates the BMP-smad1 pathway in a transcription independent manner. PLoS One, 4(6), [e6049]. https://doi.org/10.1371/journal.pone.0006049

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 journalArticle

Fulcoli, F. Gabriella ; Huynh, Tuong ; Scambler, Peter J. ; Baldini, Antonio. / Tbx1 regulates the BMP-smad1 pathway in a transcription independent manner. In: PLoS One. 2009 ; Vol. 4, No. 6.
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