Retroviral oncoprotein Tax induces processing of NF-kappa B2/p100 in T cells: evidence for the involvement of IKK alpha

I kappaB kinase (IKK) is a key mediator of NF-kappaB activation induced by various immunological signals. In T cells and most other cell types, the pr imary target of IKK is a labile inhibitor of NF-kappaB I kappaB alpha, whic h is responsible for the canonical NF-kappaB activation. Here, we show that in T cells infected with the human T-cell leukemia virus (HTLV), IKK alpha is targeted to a novel signaling pathway that mediates processing of the n f kappa b2 precursor protein p100, resulting in active production of the NF -kappaB subunit, p52. This pathogenic action is mediated by the HTLV-encode d oncoprotein Tax, which appears to act by physically recruiting IKK alpha to p100, triggering phosphorylation-dependent ubiquitylation and processing of p100. These findings suggest a novel mechanism by which Tax modulates t he NF-kappaB signaling pathway.