title: Swift is a novel BRCT domain coactivator of Smad2 in transforming growth factor beta signaling.
abstract: Transforming growth factor beta (TGFbeta) signaling is transduced via Smad2-Smad4-DNA-binding protein complexes which bind to responsive elements in the promoters of target genes. However, the mechanism of how the complexes activate the target genes is unclear. Here we identify Xenopus Swift, a novel nuclear BRCT (BRCA1 C-terminal) domain protein that physically interacts with Smad2 via its BRCT domains. We examine the activity of Swift in relation to gene activation in Xenopus embryos. Swift mRNA has an expression pattern similar to that of Smad2. Swift has intrinsic transactivation activity and activates target gene transcription in a TGFbeta-Smad2-dependent manner. Inhibition of Swift activity results in the suppression of TGFbeta-induced gene transcription and defective mesendoderm development. Blocking Swift function affects neither bone morphogenic protein nor fibroblast growth factor signaling during early development. We conclude that Swift is a novel coactivator of Smad2 and that Swift has a critical role in embryonic TGFbeta-induced gene transcription. Our results suggest that Swift may be a general component of TGFbeta signaling.
authors.affiliation: Wellcome Trust Cancer Research Campaign Institute, Cambridge CB2 1QR, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Shimizu
authors.forename: P Y
authors.initials: PY
authors.lastname: Bourillot
authors.forename: S J
authors.initials: SJ
authors.lastname: Nielsen
authors.forename: A M
authors.initials: AM
authors.lastname: Zorn
authors.forename: J B
authors.initials: JB
authors.lastname: Gurdon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019313:BRCA1 Protein / Q000737:chemistry / Q000378:metabolism*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051899:Smad2 Protein; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins
chemical_list: D019313:BRCA1 Protein; D004268:DNA-Binding Proteins; C429305:PAXIP1 protein, Xenopus; D012333:RNA, Messenger; D051899:Smad2 Protein; C497785:Smad2 protein, Xenopus; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins