The transcriptional role of Smads and FAST (FoxH1) in TGFbeta and activin signalling.
The Smad family of proteins are critical components of the TGFbeta superfamily signalling pathway. Ligand addition induces phosphorylation of specific receptor-regulated Smads, which then form heteromeric complexes with the common mediator Smad, Smad4. This complex then translocates from the cytoplasm into the nucleus. Once there, the R-Smad/Smad4 complex interacts with a variety of DNA binding proteins and is thereby targetted to a diverse array of gene promoters. The Smad-containing DNA binding complex can then positively or negatively regulate gene expression through the recruitment of co-activators and co-repressors. Xenopus FAST (now known as FoxH1) was the first Smad DNA binding partner identified and the FoxH1 family now includes related proteins from mouse, human and Zebrafish. In all organisms examined, FoxH1 is expressed primarily during the earliest stages of development and thus FoxH1 is thought to play a critical role in mediating TGFbeta superfamily signals during these early developmental stages. Other Smad partners range from those that are ubiquitously expressed to others that are present only in specific cell types or developmental stages. Thus, it is the interaction of Smads with a wide range of specific transcriptional partners that is important for the generation of diverse biological responses to TGFbeta superfamily members.
Attisano
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Department of Anatomy and Cell Biology, Medical Sciences Building, Rm. 6336, 1 King's College Circle, University of Toronto, ON, M5S 1A8, Toronto, Canada. liliana.attisano@utoronto.ca
Silvestri
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Izzi
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Labbé
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D028341:Activins / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D051858:Forkhead Transcription Factors; D006801:Humans; D009414:Nerve Growth Factors; D010750:Phosphoproteins; D011485:Protein Binding; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins; D051898:Smad1 Protein; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D051902:Smad5 Protein; D051905:Smad6 Protein; D051906:Smad7 Protein; D051904:Smad8 Protein; D015534:Trans-Activators / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D029867:Xenopus Proteins; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; C510350:FOXH1 protein, human; D051858:Forkhead Transcription Factors; C491117:Foxh1 protein, mouse; D009414:Nerve Growth Factors; D010750:Phosphoproteins; C497399:SMAD1 protein, human; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; C497797:SMAD5 protein, human; C497802:SMAD6 protein, human; C497806:SMAD7 protein, human; C107514:SMAD9 protein, human; D051785:Smad Proteins; D051898:Smad1 Protein; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; C490811:Smad4 protein, rat; D051902:Smad5 Protein; D051905:Smad6 Protein; D051906:Smad7 Protein; D051904:Smad8 Protein; C491622:Smad8 protein, Xenopus; C491621:Smad9 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C490808:smad4.1 protein, Xenopus; C117263:smad4.2 protein, Xenopus; C490809:smad4a protein, zebrafish; D028341:Activins