The role of transcription factors involved in TGFbeta superfamily signaling during development.
Recent studies of transforming growth factor-beta (TGF-beta) signaling have identified a signaling pathway that includes Ser/Thr kinase transmembrane receptors, intracellular substrates and transducers of receptor activation known as Smads, and DNA-binding transcription factors that are regulated by interaction with Smads. Both genetic and biochemical studies show that Smads are central mediators of TGF-beta signaling. How do Smads regulate the expression of target genes in the nucleus? Over the past three years, transcription factors involved in TGF-beta signaling have been identified and the molecular events in the nucleus have begun to be understood. Both Smads, which have intrinsic DNA binding activity, and additional transcription factors, act together to regulate the expression of target genes in the nucleus. Smads are relatively ubiquitously expressed in embryos during the development, while interacting transcription factors are expressed with a restricted pattern, either temporally or spatially. Therefore the developmental specificity of TGF-beta signaling may be, at least in part, determined by cell-type specific transcription factors.
Watanabe
M
M
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. mwatanbe@hms.harvard.edu
Whitman
M
M
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000502:physiology*; D005314:Embryonic and Fetal Development; D051858:Forkhead Transcription Factors; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051900:Smad3 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C510350:FOXH1 protein, human; D051858:Forkhead Transcription Factors; C491117:Foxh1 protein, mouse; D005656:Fungal Proteins; D012097:Repressor Proteins; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C102933:tin protein, Drosophila