Resource Logo

Human T-cell leukemia virus type I Tax-protein-mediated activation of NF-kappa B from p100 (NF-kappa B2)-inhibited cytoplasmic reservoirs.


Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12634-8. Unique Identifier

The human T-cell leukemia virus type I Tax protein transforms T cells through induced expression of many cellular genes, including those encoding the growth-related proteins interleukin 2 and the alpha chain of its receptor. Induction of these genes is mediated, at least in part, through Tax-dependent posttranslational activation of NF-kappa B, typically heterodimers of p50 (NF-kappa B1) and p65 (RelA). The preexisting NF-kappa B proteins are retained in the cytoplasm of cells by association with inhibitory ankyrin-motif-containing I kappa B proteins, primarily I kappa B-alpha but also including the precursor proteins p105 (NF-kappa B1) and p100 (NF-kappa B2). Here we demonstrate the existence of a previously undescribed multimeric cytoplasmic complex in which NF-kappa B dimers are associated with the p100 inhibitor in a manner dependent on the precursor protein's ankyrin domain. We also demonstrate an antagonistic effect of the Tax protein on the cytoplasmic sequestration function of p100; this in turn leads to nuclear translocation of NF-kappa B dimers liberated from multimeric complexes. Tax may exert these effects through the physical association with p100. Tax also relieves the p100-mediated inhibition of DNA binding by p50-p65 heterodimers in vitro. The results demonstrate a mechanism by which Tax may activate NF-kappa B in T cells.

Cell Compartmentation Cell Nucleus/METABOLISM Cytoplasm/METABOLISM *Gene Expression Regulation, Viral Gene Products, tax/*PHYSIOLOGY Human HTLV-I/*GENETICS In Vitro Macromolecular Systems Molecular Weight NF-kappa B/CHEMISTRY/*METABOLISM Protein Binding Tumor Cells, Cultured JOURNAL ARTICLE


Information in this article was accurate in April 30, 1995. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.