Induction of Bcl-x L Expression by Human T-Cell Leukemia Virus Type 1 Tax through NF-κB in Apoptosis-Resistant T-Cell Transfectants with Tax

Abstract

ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1) Tax is thought to play a pivotal role in immortalization of T cells. We have recently shown that the expression of Tax protected the mouse T-cell line CTLL-2 against apoptosis induced 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 that constitutive expression of bcl-xl but not bcl-2 , bcl-xs , bak , bad , or bax was associated with apoptosis resistance after IL-2 deprivation in CTLL-2 cells that expressed Tax. Transient-transfection assays showed that bcl-x promoter was transactivated by wild-type Tax. Similar effects were observed in mutant Tax retaining transactivating ability through NF-κB. Deletion or substitution of a putative NF-κB binding site identified in the bcl-x promoter significantly decreased Tax-induced transactivation. This NF-κB-like element was able to form a complex with NF-κB family proteins in vitro. Furthermore, Tax-induced transactivation of the bcl-x promoter was also diminished by the mutant IκBα, which specifically inhibits NF-κB activity. Our findings suggest that constitutive expression of Bcl-x L induced by Tax through the NF-κB pathway contributes to the inhibition of apoptosis in CTLL-2 cells after IL-2 deprivation.