A human Mad protein acting as a BMP-regulated transcriptional activator Journal Article
| Authors: | Liu, F.; Hata, A.; Baker, J. C.; Doody, J.; Cárcamo, J.; Harland, R. M.; Massagué, J. |
| Article Title: | A human Mad protein acting as a BMP-regulated transcriptional activator |
| Abstract: | The TGF-β/activin/BMP cytokine family signals through serine/threonine kinase receptors, but how the receptors transduce the signal is unknown. The Mad (Mothers against decapentaplegic) gene from Drosophila and the related Sma genes from Caenorhabditis elegans have been genetically implicated in signal ling by members of the bone-morphogenetic-protein (BMP) subfamily. We have cloned Smad1, a human homologue of Mad and Sma. Microinjection of Smad1 messenger RNA into Xenopus embryo animal caps mimics the mesoderm-ventralizing effects of BMP4. Smad1 moves into the nucleus in response to BMP4. Smad1 has transcriptional activity when fused to a heterologous DNA-binding domain, and this activity is increased by BMP4 acting through BMP-receptor types I and II. The transactivating activity resides in the conserved carboxy-terminal domain of Smad1 and is disrupted by a nonsense mutation that corresponds to null mutations found in Mad and in the related gene DPC4, a candidate tumour-suppressor gene in human pancreatic cancer. Additionally, we show that DPC4 contains a transcriptional activation domain. The results suggests that the Smad proteins are a new class of transcription factors that mediate responses to the TGF-β family. |
| Keywords: | signal transduction; dna-binding proteins; nonhuman; pancreas cancer; proteins; animals; gene; bone morphogenetic protein; smad1 protein; transforming growth factor beta; carboxy terminal sequence; embryo; transcription initiation; cell line; animal experiment; drosophila; transcription, genetic; transcription factors; molecular cloning; cloning, molecular; gene expression regulation, developmental; tumor suppressor gene; amino acid sequence; molecular sequence data; sequence homology, amino acid; cell nucleus; repressor proteins; drosophila proteins; nonsense mutation; xenopus; bone morphogenetic proteins; growth substances; basic helix-loop-helix leucine zipper transcription factors; embryonic induction; humans; human; priority journal; article |
| Journal Title: | Nature |
| Volume: | 381 |
| Issue: | 6583 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1996-06-13 |
| Start Page: | 620 |
| End Page: | 623 |
| Language: | English |
| DOI: | 10.1038/381620a0 |
| PUBMED: | 8637600 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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