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  • Original Paper
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HTLV-1 Tax oncoprotein represses the p53-mediated trans-activation function through coactivator CBP sequestration

Oncogene volume 19, pages 1491–1499 (2000)Cite this article

Abstract

The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein repressed the transcriptional activity of wild-type p53 through its N-terminal trans-activation domain. Although Tax did not directly bind to p53, this repression required the activation of CREB pathway by Tax. In contrast to a recent report by Pise-Masison et al. (1998a,b) we found that the phosphorylation of p53 on Ser 15 is not a major cause of the Tax-mediated inactivation of p53. However, Tax with a mutation in the coactivator CBP-binding site (K88A), which activates NF-κB but not the CREB pathway, could not repress the p53 trans-activation function. Moreover, Tax inhibited p53 binding to CBP in vitro and inhibited synergistic activation of transcription by CBP and p53. Thus, Tax is likely to compete with p53 in binding with CBP, thereby repressing its trans-activation function.

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Acknowledgements

We thank Dr Y Namba for the supply of anti-Tax antibody (MI 73), Dr B Vogelstein for pC53-SN3, Dr T Kiyono for pCAST2Bluc, Dr R H Goodman for pRSV mCBP-HA, Dr K Yokoyama for pCMV CBP, and Dr A J Levine for pCHDM1A. This work was supported in part by Grants-in-Aid for Scientific Research from Ministry of Education, Science, Sports and Culture of Japan.

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Authors and Affiliations

  1. Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan

    Yasuo Ariumi, Atsushi Kaida, Jye-Yee Lin, Masami Hirota, Osamu Masui & Kunitada Shimotohno

  2. Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan

    Shoji Yamaoka

  3. National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan

    Yoichi Taya

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Ariumi, Y., Kaida, A., Lin, JY. et al. HTLV-1 Tax oncoprotein represses the p53-mediated trans-activation function through coactivator CBP sequestration. Oncogene 19, 1491–1499 (2000). https://doi.org/10.1038/sj.onc.1203450

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