FAST-2 is a mammalian winged-helix protein which mediates transforming growth factor beta signals

The mechanisms by which transforming growth factor beta (TGF-beta) and rela ted ligands regulate transcription remain poorly understood. The winged-hel ix (WH) transcription factor fork head activin signal transducer 1 (FAST-1) was identified as a mediator of activin signaling in Xenopus embryos (X, C hen, M, J, Rubock, and M. Whitman, Nature 383:691-696, 1996), We have clone d a novel WH gene from the mouse which shares many properties with FAST-1, We find that this gene, which we call FAST-2, is able to mediate transcript ional activation by TGF-beta, FAST-2 also interacts directly with Smad2, a cytoplasmic protein which is translocated to the nucleus in response to TGF -beta, and forms a multimeric complex with Smad2 and Smad4 on the activin r esponse element, a high-affinity binding site for FAST-1, Analysis of the s equences of FAST-1 and FAST-2 reveals substantial protein sequence divergen ce compared to known vertebrate orthologs in the WH family. This suggests t hat FAST-2 represents a new WH gene related to FAST-1, which functions to m ediate TGF-beta signals in mammals. We have also examined the structure of the FAST-2 gene and find that it overlaps with a kinesin motor protein gene , The genes are transcribed in opposite orientations, and their transcripts overlap in the 3' untranslated region.