The tax gene product of the human T-cell leukemia virus type I(HTLV-I) induces the nuclear expression and biological function of the NF-κB/Rel family of host transcription factors although the underlying mechanism remains unclear. In the present study, we demonstrate that Tax-mediated activation of NF-κB/Rel can be inhibited by a proteasome inhibitor, suggesting the involvement of proteolytic reactions in this Tax-specific activation pathway. Transient transfection and reporter gene assays have revealed that Tax overrides the inhibitory function of IκBα in both F9 embryonal cells and Jurkat T cells. Moreover, Tax-mediated inactivation of IκBα requires a 16 amino acid sequence element located at the N-terminal region (amino acid 21-36) of IκBα, which is also required for tumor necrosis factor alpha-induced degradation of this inhibitory protein. We further demonstrate that the proteasome inhibitor also blocks the degradation of IκBα observed in HTLV-I-infected T cells. Interestingly, inhibition of IκBα degradation in these cells led to the accumulation of a phosphorylated form of IκBα. Together, these studies suggest that Tax activation of NF-κB/Rel may involve induction of phosphorylation and subsequent proteasome-mediated degradation of the inhibitor IκBα.
|Original language||English (US)|
|Number of pages||6|
|State||Published - Jan 1 1995|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cancer Research