Inhibition of apoptosis by human T-lymphotropic virus type-1 tax protein.
Deregulation of the apoptotic process can lead to pathophysiological changes that result in either degenerative diseases or cancer. Although the transactivator Tax has been established as an essential effector of human T-lymphotropic virus type-1 (HTLV-1)-mediated diseases, which include both a neurodegenerative pathology and leukemia/lymphoma, its exact role(s) in the pathogenesis remains to be clarified. Because the apoptotic potential of Tax is still being debated, we addressed this question by testing the susceptibility of Tax(-) and Tax(+) cells to apoptosis under conditions of growth factor withdrawal and Bax overexpression. Results showed that Tax(+) cells are protected from apoptosis triggered by depletion of growth factors. This protective effect seems to be the result of a block in the apoptotic program regulated by mitochondria. Furthermore, in an attempt to elucidate which transcriptional pathway activated by Tax is important in the observed Tax-induced resistance, we found that CREB/ATF activity plays a relevant role in protecting cells from apoptosis induced by Bax overexpression. All together, these data might suggest that the ability of Tax to inhibit certain apoptotic stimuli could be important in its role as a viral transforming protein.
Saggioro
Daniela
D
Department of Oncology and Surgical Sciences, Oncology Section, University of Padova, 35128 Padova, Italy. d.saggioro@unipd.it
Acquasaliente
Lidia
L
Daprai
Laura
L
Chieco-Bianchi
Luigi
L
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D045304:Cytochromes c; D016356:Gene Products, tax / Q000502:physiology*; D005822:Genetic Vectors; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D014162:Transfection
D016356:Gene Products, tax; D045304:Cytochromes c