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

Chang Rung Chen; Yibin Kang; Peter M. Siegel; Joan Massagué

doi:10.1016/S0092-8674(02)00801-2

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

Chang Rung Chen, Yibin Kang, Peter M. Siegel, Joan Massagué

Research output: Contribution to journal › Article › peer-review

424 Scopus citations

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.

Original language	English (US)
Pages (from-to)	19-32
Number of pages	14
Journal	Cell
Volume	110
Issue number	1
DOIs	https://doi.org/10.1016/S0092-8674(02)00801-2
State	Published - Jul 12 2002
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Biochemistry, Genetics and Molecular Biology

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10.1016/S0092-8674(02)00801-2

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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.",

author = "Chen, \{Chang Rung\} and Yibin Kang and Siegel, \{Peter M.\} and Joan Massagu{\'e}",

note = "Funding Information: We are indebted to A. Vidal and A. Koff for cell elutriations and supplying p107 −/− and p130 −/− mice, T. Jacks for permission to use p107 −/− and p130 −/− mice, J. Scandura and S. Nimer for pointing out the usefulness of MO-91 cells, S. Blain for valuable advice, N. Zheng and N. Pavletich for modeling Smad and E2F bound to the TIE, and M. Lindor and S. Tulley for expert technical assistance. Y.K. and P.M.S. are the recipients of postdoctoral fellowships from the Irvington Institute for Immunological Research and the Damon Runyon-Walter Winchell Cancer Fund, respectively. C.-R.C. and J.M. are a Research Associate and an Investigator, respectively, of the Howard Hughes Medical Institute.",

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AU - Massagué, Joan

N1 - Funding Information: We are indebted to A. Vidal and A. Koff for cell elutriations and supplying p107 −/− and p130 −/− mice, T. Jacks for permission to use p107 −/− and p130 −/− mice, J. Scandura and S. Nimer for pointing out the usefulness of MO-91 cells, S. Blain for valuable advice, N. Zheng and N. Pavletich for modeling Smad and E2F bound to the TIE, and M. Lindor and S. Tulley for expert technical assistance. Y.K. and P.M.S. are the recipients of postdoctoral fellowships from the Irvington Institute for Immunological Research and the Damon Runyon-Walter Winchell Cancer Fund, respectively. C.-R.C. and J.M. are a Research Associate and an Investigator, respectively, of the Howard Hughes Medical Institute.

PY - 2002/7/12

Y1 - 2002/7/12

N2 - 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.

AB - 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.

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

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