Two discrete events, human T-cell leukemia virus type I Tax oncoprotein expression and a separate stress stimulus, are required for induction of apoptosis in T-cells.
BACKGROUND
It is poorly understood why many transforming proteins reportedly enhance both cell growth (transformation) and cell death (apoptosis). At first glance, the ability to transform and the ability to engender apoptosis seem to be contradictory. Interestingly, both abilities have been widely reported in the literature for the HTLV-I Tax protein.


RESULTS
To reconcile these apparently divergent findings, we sought to understand how Tax might cause apoptosis in a Jurkat T-cell line, JPX-9. Tax expression can be induced equally by either cadmium (Cd) or zinc (Zn) in JPX-9 cells. Surprisingly, when induced by Zn, but not when induced by Cd, Tax-expression produced significant apoptosis. Under our experimental conditions, Zn but not Cd, induced SAPK (stress activated protein kinase)/JNK (Jun kinase) activation in cells. We further showed that transient over-expression of Tax-alone or Jun-alone did not induce cell death. On the other hand, co-expression of Tax plus Jun did effectively result in apoptosis.


CONCLUSIONS
We propose that Tax-expression alone in a T-cell background insufficiently accounts for apoptosis. On the other hand, Tax plus activation of a stress kinase can induce cell death. Thus, HTLV-I infection/transformation of cells requires two discrete events (i.e. oncoprotein expression and stress) to produce apoptosis.
Kasai
Takefumi
T
Laboratory of Molecular Microbiology, NIAID, National Institutes of Health, Bethesda, Maryland 20892-0460, USA. tkasai@m.kufm.kagoshima-u.ac.jp
Jeang
Kuan-Teh
KT
D017209:Apoptosis / Q000502:physiology*; D002104:Cadmium / Q000494:pharmacology; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death; D002455:Cell Division; D016356:Gene Products, tax / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D013314:Stress, Mechanical; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology / Q000821:virology*; D015032:Zinc / Q000494:pharmacology
D016356:Gene Products, tax; D002104:Cadmium; D020169:Caspases; D015032:Zinc