The transcriptional role of Smads and FAST (FoxH1) in TGF beta and activinsignalling

The Smad family of proteins are critical components of the TGF beta superfa mily signalling pathway. Ligand addition induces phosphorylation of specifi c receptor-regulated Smads. which then form heteromeric complexes with the common mediator Smad, Smad4. This complex then translocates from the cytopl asm 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 arra y of gone promoters. The Smad-containing DNA binding complex can then posit ively or negatively regulate gene expression through the recruitment of co- activators and co-repressors. Xenopus FAST (now known as FoxH1) was the fir st Smad DNA binding partner identified and the FoxH1 family now includes re lated 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 TGF beta superfa mily signals during these early developmental stages. Other Smad partners r ange from those that are ubiquitously expressed to others that are present only in specific cell types or developmental stages. Thus, it is the intera ction of Smads with a wide range of specific transcriptional partners that is important for the generation of diverse biological responses to TGF beta superfamily members. (C) 2001 Elsevier Science Ireland Ltd. All rights res erved.