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Molecular and Cellular Biology, January 1999, p. 424-430, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

FAST-2 Is a Mammalian Winged-Helix Protein Which Mediates Transforming Growth Factor beta  Signals

Bo Liu, Chang-Lin Dou, Leena Prabhu, and Eseng Lai*

Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York

Received 22 July 1998/Returned for modification 9 September 1998/Accepted 14 October 1998

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.

* Corresponding author. Mailing address: Cell Biology Program, Box 83, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021. Phone: (212) 639-2556. Fax: (212) 717-3053. E-mail: e-lai{at}ski.mskcc.org.

Molecular and Cellular Biology, January 1999, p. 424-430, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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