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

• Published in: FEBS letters 2002-11, Vol.531 (3), p.494-498
• Main Authors: Huang, Guo-Jin, Zhang, Zhi-Qing, Jin, Dong-Yan
• Format: Article
• Language: English
• Subjects: AD, Gal4 activation domain; BD, Gal4 DNA-binding domain; Biopolymers - chemistry; Biopolymers - metabolism; Gene Products, tax - physiology; GST, glutathione S-transferase; HA, hemagglutinin; HeLa Cells; HTLV-1, human T-cell leukemia virus type 1; Human T-cell leukemia virus type 1 (HTLV-1); Humans; I-kappa B Kinase; IKK, IκB kinase; IKK-γ/NEMO; IκB kinase (IKK); IκB-α phosphorylation; MBP, maltose-binding protein; NF-κB; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - metabolism; Tax oncoprotein; Two-Hybrid System Techniques; UAS, upstream activating sequence; VP, activation domain of VP16 protein from herpes simplex virus type 1
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(02)03590-1

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.