Good L, Sun S C
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey Medical Center, 17033, USA.
J Virol. 1996 May;70(5):2730-5. doi: 10.1128/JVI.70.5.2730-2735.1996.
Activation of the eukaryotic NF-kappaB/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-kappaB/Rel inhibitor IkappaBalpha. 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-kappaB/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 IkappaBbeta, another NF-kappaB/Rel cytoplasmic inhibitor that differs from IkappaBalpha in signal responses. Unlike that observed with IkappaBalpha, the degradation Of IkappaBbeta is not associated with its rapid resynthesis, apparently because of the failure of Tax to stimulate IkappaBbeta gene transcription. Thus, expression of Tax in Jurkat T cells leads to the gradual depletion of IkappaBbeta, which is correlated with the induction of c-Rel-containing kappaB binding complexes. Remarkably, in the three HTLV-1-infected T-cell lines investigated, little or no detectable amount of IkappaBbeta was found. We further demonstrate that Tax is able to override the cytoplasmic retention of c-Rel by 1kappaBbeta in transiently transfected cells. Together, these studies suggest that Tax-mediated inactivation Of IkappaBbeta may play a role in the persistent nuclear expression of c-Rel induced by HTLV-I infection.
多种细胞因子和有丝分裂原对真核生物NF-κB/Rel转录因子的激活是一个短暂的事件，这反映出这些诱导剂会触发动态的NF-κB/Rel抑制剂IκBα的降解和再合成。然而，已知人类1型T细胞白血病病毒（HTLV-1）的tax基因产物可诱导多种NF-κB/Rel因子在细胞核中持续表达，尤其是c-Rel原癌蛋白，但其潜在机制仍不清楚。在本研究中，我们证明Tax可诱导IκBβ降解，IκBβ是另一种NF-κB/Rel细胞质抑制剂，在信号反应方面与IκBα不同。与IκBα的情况不同，IκBβ的降解与其快速再合成无关，这显然是因为Tax未能刺激IκBβ基因转录。因此，Tax在Jurkat T细胞中的表达会导致IκBβ逐渐耗竭，这与含c-Rel的κB结合复合物的诱导相关。值得注意的是，在所研究的三株HTLV-1感染的T细胞系中，几乎检测不到IκBβ。我们进一步证明，Tax能够在瞬时转染的细胞中克服IκBβ对c-Rel的细胞质滞留作用。总之，这些研究表明，Tax介导的IκBβ失活可能在HTLV-1感染诱导的c-Rel细胞核持续表达中起作用。
