T. Tsukahara et al., Induction of Bcl-x(L) expression by human T-cell leukemia virus type 1 taxthrough NF-kappa B in apoptosis-resistant T-cell transfectants with tax, J VIROLOGY, 73(10), 1999, pp. 7981-7987
Human T-cell leukemia virus type 1 (HTLV-1) Tax is thought to play a pivota
l role in immortalization of T cells. We have recently shown that the expre
ssion of Tax protected the mouse T-cell line CTLL-2 against apoptosis induc
ed by interleukin-2 (IL-2) deprivation and converted its growth from being
IL-2 dependent to being IL-2 independent. In this study, we demonstrate tha
t constitutive expression of bcl-xl but not bcl-2, bcl-xs, bak, bad, or bar
was associated with apoptosis resistance after IL-2 deprivation in CTLL-2
cells that expressed Tax. Transient-transfection assays showed that bcl-x p
romoter was transactivated by wild-type Tax. Similar effects were observed
in mutant Tax retaining transactivating ability through NF-kappa B. Deletio
n or substitution of a putative NF-kappa B binding site identified in the b
cl-x promoter significantly decreased Tax-induced transactivation. This NF-
kappa B-like element was able to form a complex with NF-kappa B family prot
eins in vitro. Furthermore, Tax-induced transactivation of the bcl-x promot
er was also diminished by the mutant I kappa B alpha, which specifically in
hibits NF-kappa B activity. Our findings suggest that constitutive expressi
on of Bcl-x(L) induced by Tax through the NF-kappa B pathway contributes to
the inhibition of apoptosis in CTLL-2 cells after IL-2 deprivation.