Htlv-1 tax protein sensitizes cells to apoptotic cell death induced by dna damaging agents

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. Access through your institution Buy or subscribe This is a preview of

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Article Open access 23 August 2023 DYSREGULATION OF THE LOW-LEVEL REPLICATION STRESS RESPONSE IN TRANSFORMED CELL LINES Article Open access 06 June 2025 REFERENCES * Barry MA, Behnke CA and

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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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *

Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, 77030, Texas, TX, USA Shyan-Yuan Kao & Susan J Marriott * Program in Cell and Molecular Biology,

Baylor College of Medicine, Houston, 77030, Texas TX, USA Francene J Lemoine Authors * Shyan-Yuan Kao View author publications You can also search for this author inPubMed Google Scholar *

Francene J Lemoine View author publications You can also search for this author inPubMed Google Scholar * Susan J Marriott View author publications You can also search for this author

inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 10 January 2000 * Revised: 29

February 2000 * Accepted: 07 March 2000 * Published: 15 May 2000 * Issue Date: 27 April 2000 * DOI: https://doi.org/10.1038/sj.onc.1203559 SHARE THIS ARTICLE Anyone you share the following

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SharedIt content-sharing initiative KEYWORDS * HTLV-1 * Tax * apoptosis * nucleotide excision repair * DNA damage