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Physical and functional interactions between STAT3 and KAP1

Oncogene volume 27, pages 3054–3059 (2008)Cite this article

Abstract

Signal transducers and activators of transcription (STATs) mediate cell proliferation, differentiation and survival in immune responses, hematopoiesis, neurogenesis and other biological processes. For example, STAT3 has been reported to be constitutively activated in numerous cancer cells. To clarify the molecular mechanisms underlying the STAT activation, we performed yeast two-hybrid screening and identified KAP1/TIF1β as a novel STAT-binding partner. KAP1 is a universal corepressor protein for the Kruppel-associated box zinc-finger protein superfamily of transcriptional repressors. We found endogenous KAP1 associated with endogenous STAT3 in vivo. Importantly, small-interfering RNA-mediated reduction of KAP1 expression enhanced interleukin (IL)-6-induced STAT3-dependent transcription and gene expression. Furthermore, reduction of KAP1 expression resulted in the marked accumulation of STAT3 phosphorylated on Ser727 in the nucleus, a modification that regulates its transcriptional activation. These results indicate that KAP1 may serve as a transcriptional regulator of the IL-6/STAT3 signaling pathway.

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Acknowledgements

This study was supported in part by Sankyo Foundation of Life Science, Industrial Technology Research Grant Program in 2005 from New Energy and Industrial Technology Development Organization (NEDO) of Japan and Grant-in-Aid for scientific research from Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan

    R Tsuruma, N Ohbayashi, S Kamitani, O Ikeda, N Sato, R Muromoto, Y Sekine & T Matsuda

  2. Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan

    K Oritani

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  1. R Tsuruma
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  2. N Ohbayashi
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  3. S Kamitani
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  4. O Ikeda
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  5. N Sato
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  6. R Muromoto
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  7. Y Sekine
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  8. K Oritani
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  9. T Matsuda
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Correspondence to T Matsuda.

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Tsuruma, R., Ohbayashi, N., Kamitani, S. et al. Physical and functional interactions between STAT3 and KAP1. Oncogene 27, 3054–3059 (2008). https://doi.org/10.1038/sj.onc.1210952

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  • DOI: https://doi.org/10.1038/sj.onc.1210952

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