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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Bibliographic Details
Published in:PloS one 2009-06, Vol.4 (6), p.e6049-e6049
Main Authors: Fulcoli, F Gabriella, Huynh, Tuong, Scambler, Peter J, Baldini, Antonio
Format: Article
Language:English
Subjects:
Animals
Binding
Biophysics
Bone morphogenetic protein 4
Bone Morphogenetic Proteins - biosynthesis
Chlorocebus aethiops
COS Cells
Developmental Biology/Embryology
Developmental Biology/Molecular Development
Developmental Biology/Morphogenesis and Cell Biology
Fibroblasts
Gene expression
Gene Expression Regulation
Genetic aspects
Genetics
Growth factors
Health sciences
Heart
Mice
Mice, Inbred C57BL
Mice, Transgenic
Morphogenesis
Mutation
Population
Protein Structure, Tertiary
Proteins
Rodents
Signal Transduction
Signaling
Smad1 Protein - biosynthesis
Smad4 protein
Smad4 Protein - biosynthesis
T-Box Domain Proteins - physiology
Tbx1 protein
Thymic hypoplasia
Transcription (Genetics)
Transcription, Genetic
Transcriptional Activation
Transgenic mice
Trends
Citations: Items that cite this one
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Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0006049