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HTLV-1 Tax protein sensitizes cells to apoptotic cell death induced by DNA damaging agents

Oncogene volume 19, pages 2240–2248 (2000)Cite this article

Abstract

Transient HTLV-1 Tax expression suppresses cellular nucleotide excision repair, and this effect correlates with Tax transactivation of the proliferating cell nuclear antigen promoter. The inability to repair DNA damage typically induces apoptotic cell death. Therefore, we investigated the effect of Tax-mediated suppression of DNA repair on apoptosis in stable Tax-expressing cells. Constitutive Tax expression reduced cellular nucleotide excision repair activity compared with parental and control cells. Tax-expressing cells were also more sensitive to apoptosis induced by DNA damaging agents than control cells. Even though Tax-expressing cells displayed reduced DNA repair, they showed increased DNA replication following UV damage. These results suggest that Tax suppresses the cell's ability to repair DNA damage and stimulates DNA replication even in the presence of damage. The inability to repair DNA damage is likely to stimulate apoptotic cell death in the majority of Tax-expressing cells while the ability to promote DNA replication may also allow the survival of a small population of cells. We propose that together these effects contribute to the monoclonal nature and low efficiency of HTLV-1 transformation.

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Acknowledgements

We thank Drs Robert Weiss and Ronald Javier for providing CREF, CREF-Tax and CREF-neo cells. We gratefully acknowledge Dr Betty Slagle and Yahua Chen for critical evaluation of the manuscript. We also thank Caroline Petrin for secretarial support, Michael Pastorello for technical assistance, and Luna Chang for statistical assistance. These studies were supported by Public Health Service grant CA-77371 to SJ Marriott from the National Cancer Institute. FJ Lemoine was supported, in part, by NIH training grant CA09197.

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  1. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, 77030, Texas, TX, USA

    Shyan-Yuan Kao & Susan J Marriott

  2. Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, 77030, Texas TX, USA

    Francene J Lemoine

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Kao, SY., Lemoine, F. & Marriott, S. HTLV-1 Tax protein sensitizes cells to apoptotic cell death induced by DNA damaging agents. Oncogene 19, 2240–2248 (2000). https://doi.org/10.1038/sj.onc.1203559

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