Functional Specificity of the Xenopus T-Domain Protein Brachyury Is Conferred by Its Ability to Interact with Smad1

Members of the T-box gene family play important and diverse roles in development and disease. Here, we study the functional specificities of the Xenopus T-domain proteins Xbra and VegT, which differ in their abilities to induce gene expression in prospective ectodermal tissue. In particular, VegT in...

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Veröffentlicht in:Developmental cell 2005-04, Vol.8 (4), p.599-610
Hauptverfasser: Messenger, Nigel J., Kabitschke, Christin, Andrews, Robert, Grimmer, Donna, Miguel, Ricardo Núñez, Blundell, Tom L., Smith, James C., Wardle, Fiona C.
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container_end_page 610
container_issue 4
container_start_page 599
container_title Developmental cell
container_volume 8
creator Messenger, Nigel J.
Kabitschke, Christin
Andrews, Robert
Grimmer, Donna
Miguel, Ricardo Núñez
Blundell, Tom L.
Smith, James C.
Wardle, Fiona C.
description Members of the T-box gene family play important and diverse roles in development and disease. Here, we study the functional specificities of the Xenopus T-domain proteins Xbra and VegT, which differ in their abilities to induce gene expression in prospective ectodermal tissue. In particular, VegT induces strong expression of goosecoid whereas Xbra cannot. Our results indicate that Xbra is unable to induce goosecoid because it directly activates expression of Xom, a repressor of goosecoid that acts downstream of BMP signaling. We show that the inability of Xbra to induce goosecoid is imposed by an N-terminal domain that interacts with the C-terminal MH2 domain of Smad1, a component of the BMP signal transduction pathway. Interference with this interaction causes ectopic activation of goosecoid and anteriorization of the embryo. These findings suggest a mechanism by which individual T-domain proteins may interact with different partners to elicit a specific response.
doi_str_mv 10.1016/j.devcel.2005.03.001
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subjects Amino Acid Sequence
Animals
Biological and medical sciences
Bone Morphogenetic Proteins - metabolism
Cell differentiation, maturation, development, hematopoiesis
Cell physiology
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Ectoderm - cytology
Ectoderm - physiology
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Developmental
Goosecoid Protein
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
Models, Molecular
Molecular and cellular biology
Molecular Sequence Data
Morphogenesis
Protein Conformation
Protein Structure, Tertiary
Repressor Proteins - genetics
Repressor Proteins - metabolism
Sequence Alignment
Signal Transduction - physiology
Smad Proteins
Smad1 Protein
T-Box Domain Proteins - chemistry
T-Box Domain Proteins - genetics
T-Box Domain Proteins - metabolism
Trans-Activators - chemistry
Trans-Activators - genetics
Trans-Activators - metabolism
Transcription Factors - genetics
Transcription Factors - metabolism
Two-Hybrid System Techniques
Xenopus laevis - embryology
Xenopus laevis - physiology
Xenopus Proteins - genetics
Xenopus Proteins - metabolism
title Functional Specificity of the Xenopus T-Domain Protein Brachyury Is Conferred by Its Ability to Interact with Smad1
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