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 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.
Messenger
Nigel J
NJ
Wellcome Trust/Cancer Research UK Gurdon Institute, Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, United Kingdom.
Kabitschke
Christin
C
Andrews
Robert
R
Grimmer
Donna
D
Núñez Miguel
Ricardo
R
Blundell
Tom L
TL
Smith
James C
JC
Wardle
Fiona C
FC
D000595:Amino Acid Sequence; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004475:Ectoderm / Q000166:cytology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D051956:Goosecoid Protein; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009024:Morphogenesis; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins; D051898:Smad1 Protein; D020825:T-Box Domain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology / Q000502:physiology*
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C497992:GSC protein, human; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; C497402:MXD1 protein, Xenopus; D012097:Repressor Proteins; C497399:SMAD1 protein, human; D051785:Smad Proteins; D051898:Smad1 Protein; D020825:T-Box Domain Proteins; C116765:TBXT protein, Xenopus; D015534:Trans-Activators; D014157:Transcription Factors; C103966:VegT protein, Xenopus; D029867:Xenopus Proteins; C099992:ventx2.1 protein, Xenopus