title: Xenopus Smad4beta is the co-Smad component of developmentally regulated transcription factor complexes responsible for induction of early mesodermal genes.
abstract: Smad4 is defined as the common-mediator Smad (co-Smad) required for transducing signals for all TGF-beta superfamily members. This paper describes two Smad4s in Xenopus: XSmad4alpha, which is probably the Xenopus orthologue of human Smad4, and a distinct family member, XSmad4beta, which differs primarily at the extreme N-terminus and in the linker region. Both XSmad4s act as co-Smads, forming ligand-dependent complexes with receptor-regulated Smads 1 and 2 and synergizing with them to activate transcription of mesodermal genes in Xenopus embryos. The two XSmad4 genes have reciprocal temporal expression patterns in Xenopus embryos and are expressed in varying ratios in adult tissues, suggesting distinct functional roles in vivo. XSmad4beta is the predominant maternal co-Smad and we go on to demonstrate its role in the transcriptional regulation of early mesodermal genes. We have identified two distinct nuclear complexes that bind the activin-responsive element of the Xenopus Mix.2 promoter: one formed in response to high levels of activin signaling and the other activated by endogenous signaling pathways. Using specific antisera we demonstrate the presence of endogenous XSmad4beta and also XSmad2 in both of these complexes, and our data indicate that the DNA-binding components of the complexes are different. Furthermore, we show that the presence of these complexes in the nucleus perfectly correlates with the transcriptional activity of the target gene, Mix.2, and we show that one of the XSmad4beta-containing transcription factor complexes undergoes a developmentally regulated nuclear translocation.
authors.affiliation: Ludwig Institute for Cancer Research, 91 Riding House Street, London, W1P 8BT, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Howell
authors.forename: F
authors.initials: F
authors.lastname: Itoh
authors.forename: C E
authors.initials: CE
authors.lastname: Pierreux
authors.forename: S
authors.initials: S
authors.lastname: Valgeirsdottir
authors.forename: S
authors.initials: S
authors.lastname: Itoh
authors.forename: P
authors.initials: P
authors.lastname: ten Dijke
authors.forename: C S
authors.initials: CS
authors.lastname: Hill
mesh_terms: D028341:Activins; D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D007265:Inhibins / Q000378:metabolism; D008648:Mesoderm / Q000502:physiology*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D010957:Plasmids; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051785:Smad Proteins; D051899:Smad2 Protein; D051901:Smad4 Protein; D013997:Time Factors; D014018:Tissue Distribution; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins
chemical_list: D004268:DNA-Binding Proteins; C102067:FOXH1 protein, Xenopus; C510350:FOXH1 protein, human; D051858:Forkhead Transcription Factors; C491117:Foxh1 protein, mouse; D009414:Nerve Growth Factors; D051785:Smad Proteins; D051899:Smad2 Protein; C497785:Smad2 protein, Xenopus; D051901:Smad4 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C490808:smad4.1 protein, Xenopus; C117263:smad4.2 protein, Xenopus; D028341:Activins; D007265:Inhibins