Abstract
Background:
Activator protein-1 (AP-1) is a mediator of BMP or FGF signaling during Xenopus embryogenesis. However, specific role of AP-1 in activin signaling has not been elucidated during vertebrate development.
Methodology/principal findings:
We provide new evidence showing that overexpression of heterodimeric AP-1 comprised of c-jun and c-fos (AP-1(c-Jun/c-Fos)) induces the expression of BMP-antagonizing organizer genes (noggin, chordin and goosecoid) that were normally expressed by high dose of activin. AP-1(c-Jun/c-Fos) enhanced the promoter activities of organizer genes but reduced that of PV.1, a BMP4-response gene. A loss of function study clearly demonstrated that AP-1(c-Jun/c-Fos) is required for the activin-induced organizer and neural gene expression. Moreover, physical interaction of AP-1(c-Jun/c-Fos) and Smad3 cooperatively enhanced the transcriptional activity of goosecoid via direct binding on this promoter. Interestingly, Smad3 mutants at c-Jun binding site failed in regulation of organizer genes, indicating that these physical interactions are specifically necessary for the expression of organizer genes.
Conclusions/significance:
AP-1(c-Jun/c-Fos) plays a specific role in organizer gene expression in downstream of activin signal during early Xenopus embryogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activins / genetics
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Activins / metabolism*
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Animals
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Blotting, Western
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Bone Morphogenetic Protein 4 / genetics
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Bone Morphogenetic Protein 4 / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Chromatin Immunoprecipitation
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Embryo, Nonmammalian / cytology
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Embryo, Nonmammalian / metabolism*
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Gene Expression Regulation*
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Glycoproteins / genetics
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Glycoproteins / metabolism
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Goosecoid Protein / genetics
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Goosecoid Protein / metabolism
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Immunoprecipitation
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In Situ Hybridization
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism
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Luciferases / metabolism
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Organizers, Embryonic / metabolism*
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Promoter Regions, Genetic
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Protein Binding
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Protein Multimerization
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Proto-Oncogene Proteins c-fos / genetics
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Proto-Oncogene Proteins c-fos / metabolism*
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Proto-Oncogene Proteins c-jun / genetics
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Proto-Oncogene Proteins c-jun / metabolism*
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RNA, Messenger / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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Smad3 Protein / genetics
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Smad3 Protein / metabolism
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T-Box Domain Proteins / genetics
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T-Box Domain Proteins / metabolism
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Transcription Factor AP-1 / genetics
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Transcription Factor AP-1 / metabolism*
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Transcriptional Activation
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Xenopus Proteins / genetics
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Xenopus Proteins / metabolism
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Xenopus laevis
Substances
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Bone Morphogenetic Protein 4
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Carrier Proteins
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Glycoproteins
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Goosecoid Protein
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Intercellular Signaling Peptides and Proteins
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Proto-Oncogene Proteins c-fos
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Proto-Oncogene Proteins c-jun
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RNA, Messenger
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Smad3 Protein
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T-Box Domain Proteins
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TBXT protein, Xenopus
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Transcription Factor AP-1
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Xenopus Proteins
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Activins
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noggin protein
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chordin
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Luciferases