FAST-2 is a mammalian winged-helix protein which mediates transforming growth factor β signals Journal Article


Authors: Liu, B.; Dou, C. L.; Prabhu, L.; Lai, E.
Article Title: FAST-2 is a mammalian winged-helix protein which mediates transforming growth factor β signals
Abstract: The mechanisms by which transforming growth factor β (TGF-β) 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-β. FAST-2 also interacts directly with Smad2, a cytoplasmic protein which is translocated to the nucleus in response to TGF- β, 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-β 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.
Keywords: signal transduction; sequence analysis; dna-binding proteins; nonhuman; forkhead transcription factors; animals; mice; gene expression; smad2 protein; smad3 protein; transforming growth factor beta; transcription initiation; transcription factor; cos cells; transcription factors; molecular cloning; cloning, molecular; transcription regulation; amino acid sequence; molecular sequence data; nucleotide sequence; base sequence; trans-activators; mammals; luciferases; protein determination; dna, complementary; xenopus; activin; activins; priority journal; article; inhibins; genes, overlapping
Journal Title: Molecular and Cellular Biology
Volume: 19
Issue: 1
ISSN: 0270-7306
Publisher: American Society for Microbiology  
Date Published: 1999-01-01
Start Page: 424
End Page: 430
Language: English
PUBMED: 9858566
PROVIDER: scopus
PMCID: PMC83900
DOI: 10.1128/MCB.19.1.424
DOI/URL:
Notes: Article -- Export Date: 16 August 2016 -- Source: Scopus
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MSK Authors
  1. Eseng Lai
    45 Lai
  2. Changlin   Dou
    5 Dou
  3. Bo   Liu
    2 Liu
  4. Leena Madhukar Prabhu
    1 Prabhu