HTLV-1 Tax protein sensitizes cells to apoptotic cell death induced by DNA damaging agents.
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.
Kao
S Y
SY
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
Lemoine
F J
FJ
Mariott
S J
SJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication; D004347:Drug Interactions; D005347:Fibroblasts / Q000166:cytology; D005472:Fluorouracil / Q000494:pharmacology; D016356:Gene Products, tax / Q000494:pharmacology*; D015368:Human T-lymphotropic virus 1; D009153:Mutagens / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D051381:Rats; D014466:Ultraviolet Rays; D017735:Virus Latency
D016356:Gene Products, tax; D009153:Mutagens; D018809:Proliferating Cell Nuclear Antigen; D002945:Cisplatin; D005472:Fluorouracil