E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression.

Smad3 is a direct mediator of transcriptional activation by the TGFbeta 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 TGFbeta, 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 TGFbeta receptor signals upstream of cdk. Smad proteins therefore mediate transcriptional activation or repression depending on their associated partners.
Mesh Terms:
Active Transport, Cell Nucleus, Animals, Binding Sites, COS Cells, Cell Cycle, Cell Cycle Proteins, Cercopithecus aethiops, DNA-Binding Proteins, E2F4 Transcription Factor, E2F5 Transcription Factor, Gene Silencing, Humans, Nuclear Proteins, Promoter Regions, Genetic, Proto-Oncogene Proteins c-myc, Receptors, Transforming Growth Factor beta, Retinoblastoma-Like Protein p107, Smad3 Protein, Trans-Activators, Transcription Factor DP1, Transcription Factors, Transcription, Genetic, Transforming Growth Factor beta, Tumor Cells, Cultured
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Date: Jul. 12, 2002
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