Dual role of the Smad4/DPC4 tumor suppressor in TGFβ-inducible transcriptional complexes Journal Article
| Authors: | Liu, F.; Pouponnot, C.; Massagué, J. |
| Article Title: | Dual role of the Smad4/DPC4 tumor suppressor in TGFβ-inducible transcriptional complexes |
| Abstract: | Upon ligand binding, the receptors of the TGFβ family phosphorylate Smad proteins, which then move into the nucleus where they activate transcription. To carry out this function, the receptor-activated Smads 1 and 2 require association with the product of deleted in pancreatic carcinoma, locus 4 (DPC4), Smad4. We investigated the step at which Smad4 is required for transcriptional activation. Smad4 is not required for nuclear translocation of Smads 1 or 2, or for association of Smad2 with a DNA binding partner, the winged helix protein FAST-1. Receptor-activated Smad2 takes Smad4 into the nucleus where they form a complex with FAST-1 that requires these three components to activate transcription. Smad4 contributes two functions: Through its amino-terminal domain, Smad4 promotes binding of the Smad2/Smad4/FAST-1 complex to DNA; through its carboxy-terminal domain, Smad4 provides an activation function required for Smad1 or Smad2 to stimulate transcription. The dual function of Smad4 in transcriptional activation underscores its central role in TGFβ signaling. |
| Keywords: | signal transduction; controlled study; gene deletion; dna-binding proteins; nonhuman; forkhead transcription factors; animal cell; animals; smad1 protein; smad2 protein; transforming growth factor beta; tumor cells, cultured; structure-activity relationship; cos cells; animalia; transcription factors; tumor suppressor gene; dna; transcription regulation; molecular sequence data; recombinant fusion proteins; protein-serine-threonine kinases; receptors, transforming growth factor beta; smad proteins; gene control; binding sites; trans-activators; cell nucleus; genes, tumor suppressor; transcriptional regulation; transforming growth factor alpha; tumor suppressors; xenopus; bmp; smad4 protein; xenopus proteins; smad; tgfΒ; trans-activation (genetics); activin receptors, type i; activin; activins; humans; priority journal; article; inhibins |
| Journal Title: | Genes and Development |
| Volume: | 11 |
| Issue: | 23 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 1997-12-01 |
| Start Page: | 3157 |
| End Page: | 3167 |
| Language: | English |
| PUBMED: | 9389648 |
| PROVIDER: | scopus |
| PMCID: | PMC316747 |
| DOI: | 10.1101/gad.11.23.3157 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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