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The interaction of HTLV-1 Tax with HDAC1 negatively regulates the viral gene expression

Oncogene volume 21, pages 7241–7246 (2002)Cite this article

Abstract

Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are known to interact with several transcription factors and regulate their transcriptional activities. The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein activates transcription from its long terminal repeat (LTR) through interaction with cellular factors such as CREB and a transcriptional coactivator CBP/p300. However, little is known about the interaction between Tax and transcriptional repressors. Here, we demonstrate the physical and functional interaction between Tax and HDAC1. We found that HDAC1 represses the trans-activation function of Tax in 293T and MT4 cells. However, this repression was restored by treatment with an HDAC inhibitor, Trichostatin A. We also observed physical interaction between Tax and HDAC1 both in vitro and in vivo. The N-terminal region of HDAC1 (amino acid residues 28–97) was required for this binding. Moreover, HDAC1 inhibited the synergistic trans-activation of Tax observed on ectopic expression of CBP. However, this repression was relieved by overexpression of CBP. Thus, HDAC1 is likely to compete with CBP in binding with Tax and functions as a negative regulator for the transcriptional activation by Tax.

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Acknowledgements

We thank Dr T Kouzarides for providing pcDNA3-HD1F, Dr M Hatanaka for pH2R-Tax, Dr I Talianidis for CMV-CBP and Dr Y Namba for anti-Tax mAb MI73. We also thank Dr M Hijikata, Dr T Ohshima and Mr A Kaida for helpful discussion, and Ms N Umehara and Ms JY Lin for helping our work. This work was supported by Grants-in-Aid for Scientific Research from Ministry of Education, Culture, Sports, Science and Technology.

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  1. Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, 606-8507, Kyoto, Japan

    Takeshi Ego, Yasuo Ariumi & Kunitada Shimotohno

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  1. Takeshi Ego
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  2. Yasuo Ariumi
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  3. Kunitada Shimotohno
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Correspondence to Kunitada Shimotohno.

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Ego, T., Ariumi, Y. & Shimotohno, K. The interaction of HTLV-1 Tax with HDAC1 negatively regulates the viral gene expression. Oncogene 21, 7241–7246 (2002). https://doi.org/10.1038/sj.onc.1205701

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