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HTLV-1 HBZ suppresses AP-1 activity by impairing both the DNA-binding ability and the stability of c-Jun protein

Oncogene volume 24, pages 1001–1010 (2005)Cite this article

Abstract

Disruption of transcriptional control of cellular genes by human T-cell leukemia virus type-1 (HTLV-1) is thought to be associated, at least in part, with the development of adult T-cell leukemia. It has been reported that activating protein-1 (AP-1) is dysregulated by HTLV-1 infection. HTLV-1-encoded Tax elevates AP-1 activity through the induction of AP-1 family member gene expression, including c-Jun, JunD, c-Fos, and Fra-1. However, the precise mechanism by which HTLV-1 regulates AP-1 activity remains to be addressed. Recently, a novel viral protein named HTLV-1 basic leucine-zipper factor, HBZ, has been shown to interact with c-Jun and repress c-Jun-mediated transcription by abrogating its DNA-binding activity. In the course of investigating HBZ function, we found that HBZ reduced the steady-state levels of c-Jun, and the levels were restored by treatment with a proteasome inhibitor. Together, this indicates that HBZ promotes c-Jun degradation through a proteasome-dependent pathway. Furthermore, HBZ deletion mutants revealed that both the N-terminal and leucine-zipper region of HBZ were required for the elimination of c-Jun. These results suggest dual effects of HBZ on the suppression of AP-1 activity by inhibiting c-Jun function, which may contribute to the dysregulation of cell proliferation.

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Acknowledgements

We thank Drs N Mukaida and M Hatanaka for p2 × AP-1-Luc and pH2R-Tax, respectively. We also thank members of the Laboratory of Human Tumor Viruses for helpful advice and discussion. This work was supported by grants-in-aid for cancer research and for the second-term comprehensive 10-year strategy for cancer control from the Ministry of Health, Labor, and Welfare, and grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology, and grants-in-aid of research for the future from the Japanese Society for the Promotion of Science. JM was supported by the 21st Century COE Program of the Ministry of Education, Culture, Sports, Science and Technology to Graduate School of Biostudies and Institute for Virus Research, Kyoto University.

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

    Jun Matsumoto, Takayuki Ohshima, Osamu Isono & Kunitada Shimotohno

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  1. Jun Matsumoto
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  2. Takayuki Ohshima
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Correspondence to Takayuki Ohshima or Kunitada Shimotohno.

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Matsumoto, J., Ohshima, T., Isono, O. et al. HTLV-1 HBZ suppresses AP-1 activity by impairing both the DNA-binding ability and the stability of c-Jun protein. Oncogene 24, 1001–1010 (2005). https://doi.org/10.1038/sj.onc.1208297

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