Persistent activation of NF-kappa B/Rel by human T-cell leukemia virus type 1 tax involves degradation of I kappa B beta.
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.
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Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey Medical Center, 17033, USA.
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D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D016356:Gene Products, tax / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D016356:Gene Products, tax; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D011994:Recombinant Proteins; D014157:Transcription Factors