Persistent activation of NF-κB/Rel by human T-cell leukemia virus type 1 tax involves degradation of IκBβ

Activation of the eukaryotic NF-κB/Rel transcription factors by various cytokines and mitogens is a transient event, reflecting the fact that these inducers trigger the degradation and resynthesis of the dynamic NF-κB/Rel inhibitor IκBα. However, the tax gene product of the human T-cell leukemia virus type 1 (HTLV-1) is known to induce the persistent nuclear expression of various NF-κB/Rel factors, especially the c-Rel proto-oncoprotein, although the underlying mechanism remains unclear. In the present study, we demonstrate that Tax induces the degradation of IκBβ, another NF-κB/Rel cytoplasmic inhibitor that differs from IκBα in signal responses. Unlike that observed with IκBα, the degradation of IκBβ is not associated with its rapid resynthesis, apparently because of the failure of Tax to stimulate IκBβ gene transcription. Thus, expression of Tax in Jurkat T cells leads to the gradual depletion of IκBβ, which is correlated with the induction of c- Rel-containing κB binding complexes. Remarkably, in the three HTLV-1- infected T-cell lines investigated, little or no detectable amount of IκBβ was found. We further demonstrate that Tax is able to override the cytoplasmic retention of c-Rel by IκBβ in transiently transfected cells. Together, these studies suggest that Tax-mediated inactivation of IκBβ may play a role in the persistent nuclear expression of c-Rel induced by HTLV-1 infection.