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XB-ART-13795
Mol Cell Biol January 1, 1999; 19 (1): 424-30.

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

Liu B , Dou CL , Prabhu L , Lai E .


Abstract
The mechanisms by which transforming growth factor beta (TGF-beta) and related ligands regulate transcription remain poorly understood. The winged-helix (WH) transcription factor fork head activin signal transducer 1 (FAST-1) was identified as a mediator of activin signaling in Xenopus embryos (X. Chen, M. J. Rubock, and M. Whitman, Nature 383:691-696, 1996). We have cloned 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 transcriptional 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 response element, a high-affinity binding site for FAST-1. Analysis of the sequences of FAST-1 and FAST-2 reveals substantial protein sequence divergence compared to known vertebrate orthologs in the WH family. This suggests that FAST-2 represents a new WH gene related to FAST-1, which functions to mediate 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.

PubMed ID: 9858566
PMC ID: PMC83900
Article link: Mol Cell Biol
Grant support: [+]
Genes referenced: smad2 smad4.1 smad4.2

References [+] :
Ang, HNF-3 beta is essential for node and notochord formation in mouse development. 1994, Pubmed


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