E2F4/5 and p107 as Smad cofactors linking the TGFβ receptor to c-myc repression Journal Article
| Authors: | Chen, C. R.; Kang, Y.; Siegel, P. M.; Massagué, J. |
| Article Title: | E2F4/5 and p107 as Smad cofactors linking the TGFβ receptor to c-myc repression |
| Abstract: | Smad3 is a direct mediator of transcriptional activation by the TGFβ receptor. Its target genes in epithelial cells include cyclin-dependent kinase inhibitors that generate a cytostatic reponse. We defined how, in the same context, Smad3 can also mediate transcriptional repression of the growth-promoting gene c-myc. A complex containing Smad3, the transcription factors E2F4/5 and DP1, and the corepressor p107 preexists in the cytoplasm. In response to TGFβ, this complex moves into the nucleus and associates with Smad4, recognizing a composite Smad-E2F site on c-myc for repression. Previously known as the ultimate recipients of cdk regulatory signals, E2F4/5 and p107 act here as transducers of TGFβ receptor signals upstream of cdk. Smad proteins therefore mediate transcriptional activation or repression depending on their associated partners. |
| Keywords: | signal transduction; controlled study; human cell; dna-binding proteins; nonhuman; protein function; animal cell; animals; cell cycle proteins; gene targeting; cell cycle; complex formation; smad protein; smad3 protein; transforming growth factor beta; protein protein interaction; transcription, genetic; tumor cells, cultured; cercopithecus aethiops; cos cells; animalia; transcription factors; nuclear proteins; transcription regulation; transcription factor e2f; myc protein; gene repression; protein transport; transforming growth factor beta receptor; receptors, transforming growth factor beta; epithelium cell; cytoplasm; active transport, cell nucleus; binding sites; trans-activators; cell nucleus; gene silencing; proto-oncogene proteins c-myc; isoprotein; protein p107; retinoblastoma-like protein p107; cytostasis; transcription factor dp1; promoter regions (genetics); humans; human; priority journal; article; e2f4 transcription factor; e2f5 transcription factor |
| Journal Title: | Cell |
| Volume: | 110 |
| Issue: | 1 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2002-07-12 |
| Start Page: | 19 |
| End Page: | 32 |
| Language: | English |
| DOI: | 10.1016/s0092-8674(02)00801-2 |
| PUBMED: | 12150994 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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