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NF-κB signaling mediates the induction of MTA1 by hepatitis B virus transactivator protein HBx

Oncogene volume 29, pages 1179–1189 (2010)Cite this article

Abstract

Metastasis-associated protein 1 (MTA1), a master chromatin modifier, has been shown to regulate cancer progression and is widely upregulated in human cancer, including hepatitis B virus-associated hepatocellular carcinomas (HCCs). Here we provide evidence that hepatitis B virus transactivator protein HBx stimulates the expression of MTA1 but not of MTA2 or MTA3. The underlying mechanism of HBx stimulation of MTA1 involves HBx targeting of transcription factor nuclear factor (NF)-κB and the recruitment of HBx/p65 complex to the NF-κB consensus motif on the relaxed MTA1 gene chromatin. We also discovered that MTA1 depletion in HBx-expressing cells severely impairs the ability of HBx to stimulate NF-κB signaling and the expression of target proinflammatory molecules. Furthermore, the presence of HBx in HBx-infected HCCs correlated well with increased MTA1 and NF-κB-p65. Collectively, these findings revealed a previously unrecognized integral role of MTA1 in HBx stimulation of NF-κB signaling and consequently, the expression of NF-κB targets gene products with functions in inflammation and tumorigenesis.

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Acknowledgements

We thank Aleem Siddiqui for pCMVXF and pCMV-Core constructs, Ranjit Banerjee for the HVC core plasmid, Amanda J Hodgson for technical assistance and Xuemei Wang for statistical analysis. The work was supported by NIH Grant CA98823 (RK). Work in Dr Betty L Slagle laboratory is supported by the NIH Grant 95388.

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Author notes

  1. T M Bui-Nguyen and S B Pakala: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Institute of Coregulator Biology, The George Washington University, Washington, DC, USA

    T M Bui-Nguyen, S B Pakala, R D Sirigiri & R Kumar

  2. Department of Molecular and Cellular Oncology, MD Anderson Cancer Center, Houston, TX, USA

    W Xia & M-C Hung

  3. Center for Molecular Medicine, Graduate Institute of Cancer Biology, China Medical University and Hospital, Taichung, Taiwan

    M-C Hung

  4. Department of Gastroenterology, G.P. Pant Hospital, Institute of Liver and Biliary Sciences, New Delhi, India

    S K Sarin

  5. Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

    S K Sarin

  6. Virology Laboratory, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

    V Kumar

  7. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA

    B L Slagle

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  1. T M Bui-Nguyen
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Correspondence to R Kumar.

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

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Bui-Nguyen, T., Pakala, S., Sirigiri, R. et al. NF-κB signaling mediates the induction of MTA1 by hepatitis B virus transactivator protein HBx. Oncogene 29, 1179–1189 (2010). https://doi.org/10.1038/onc.2009.404

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