p53-independent induction of apoptosis by the HTLV-I tax protein following UV irradiation.
Human T cell leukemia virus type 1 (HTLV-1) encodes a transforming protein, Tax. Tax is a promiscuous viral transactivator involved in both cell growth and death control. We have previously shown that Tax sensitizes cells to apoptosis induced by DNA-damaging agents and this report further characterizes the Tax-mediated apoptosis pathway. We found that Tax-mediated apoptosis in response to UV irradiation was inhibited by Bcl-2 and Bcl-X(L) overexpression and by treatment with the caspase inhibitor z-VAd-FMK. Since Tax has been shown to functionally inactivate the apoptosis regulator p53, the effect of Tax on apoptosis in the absence of p53 was examined. In these studies, Tax sensitized p53-negative cells to apoptose, suggesting that Tax can mediate a p53-independent form of apoptosis. In addition, cells expressing both Tax and p53 displayed higher levels of apoptosis than cells expressing either protein alone, suggesting that the apoptosis-inducing activities of Tax and p53 are not completely overlapping. These observations demonstrate that Tax can utilize a p53-independent mechanism to induce apoptotic cell death following UV irradiation.
Kao
S Y
SY
Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Lemoine
F J
FJ
Marriott
S J
SJ
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D061945:Caspase Inhibitors; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D014466:Ultraviolet Rays; D051020:bcl-X Protein
D000590:Amino Acid Chloromethyl Ketones; C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; C494813:Bcl2l1 protein, rat; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D016356:Gene Products, tax; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone