Stimulation of IKK‐γ oligomerization by the human T‐cell leukemia virus oncoprotein Tax

Abstract

Human T-cell leukemia virus type 1 oncoprotein Tax activates NF-κB through direct binding to IKK-γ, the regulatory component of the IκB kinase complex. Mechanisms by which IKK-γ adapts the Tax signal to the IκB kinase are poorly understood. Here we demonstrate that IKK-γ forms homodimer and homotrimer both in vitro and in yeast or mammalian cells through a C-terminal domain comprising amino acids 251–419. In contrast, Tax protein targets a central region of IKK-γ, which consists of amino acids 201–250. Interestingly, Tax stimulates the oligomerization of IKK-γ, likely through direct binding. Taken together, our findings suggest a new model of Tax activation of NF-κB, in which Tax interacts with IKK-γ to stimulate its oligomerization.