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Title 

SRF is a nuclear repressor of Smad3-mediated TGF-beta signaling

 

SRF의 Smad3-mediated TGF 신호전달에서의 핵내억제 작용

Authors 

Ho Jae LeeC H YunS H LimB C KimK G BaikJ M KimW H KimS J Kim

Publisher 

Nature Publishing Group

Issue Date 

2007

Citation 

Oncogene, vol. 26, no. 2, pp. 173-185

Keywords 

signalingsmadSRFsuppressionTGF-βtranscriptioncyclin dependent kinase inhibitor 1cyclin dependent kinase inhibitor 2BDNAserum response factor

Abstract 

Serum response factor (SRF) is a widely expressed transcription factor involved in immediate-early and tissue-specific gene expression, cell proliferation and differentiation. We defined a new role of SRF as a nuclear repressor of the tumor growth factor β1 (TGF-β1) growth-inhibitory signal during cell proliferation. We show that SRF significantly inhibits the TGF-β1/Smad-dependent transcription by associating with Smad3. SRF causes resistance to the TGF-β1 cytostatic response by directly repressing the Smad transcriptional activity and Smad binding to DNA. Furthermore, we demonstrated that overexpression of SRF markedly decreases the level of Smad3 complex binding to the promoters of Smad3 target genes, p15INK4b and p21Cip1. This leads to the inhibition of expression of TGF-β1-responsive genes. SRF therefore acts as a nuclear repressor of Smad3-mediated TGF-β1 signaling.

ISSN 

0950-9232

Link 

http://dx.doi.org/10.1038/sj.onc.1209774

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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