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

Oncogene volume 26, pages 173–185 (2007)Cite this article

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.

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Acknowledgements

This work was supported by funds from the intramural program of National Cancer Institute. We thank J Massaguè for 3TP-Lux, S Kern for SBE4-luc, JH Kim for SRF constructs and AB Roberts for the critical reading of the manuscript.

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Author notes

  1. J-M Kim

    Present address: Dr Department of Pathology, Inha University College of Medicine, Inchon, Korea

Authors and Affiliations

  1. Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD, USA

    H-J Lee, C-H Yun, S H Lim, B-C Kim, K G Baik, J-M Kim & S-J Kim

  2. Division of Molecular Therapeutics, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea

    H-J Lee

  3. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea

    C-H Yun

  4. Division of Life Sciences, Kangwon National University, Chuncheon, Korea

    B-C Kim

  5. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

    W-H Kim

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Correspondence to S-J Kim.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Lee, HJ., Yun, CH., Lim, S. et al. SRF is a nuclear repressor of Smad3-mediated TGF-β signaling. Oncogene 26, 173–185 (2007). https://doi.org/10.1038/sj.onc.1209774

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