Yin M J, Christerson L B, Yamamoto Y, Kwak Y T, Xu S, Mercurio F, Barbosa M, Cobb M H, Gaynor R B
Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas 75235-8594, USA.
Cell. 1998 May 29;93(5):875-84. doi: 10.1016/s0092-8674(00)81447-6.
NF-kappaB, a key regulator of the cellular inflammatory and immune response, is activated by the HTLV-I transforming and transactivating protein Tax. We show that Tax binds to the amino terminus of the protein kinase MEKK1, a component of an IkappaB kinase complex, and stimulates MEKK1 kinase activity. Tax expression increases the activity of IkappaB kinase beta (IKKbeta) to enhance phosphorylation of serine residues in IkappaB alpha that lead to its degradation. Dominant negative mutants of both IKKbeta and MEKK1 prevent Tax activation of the NF-kappaB pathway. Furthermore, recombinant MEKK1 stimulates IKKbeta phosphorylation of IkappaB alpha. Thus, Tax-mediated increases in NF-kappaB nuclear translocation result from direct interactions of Tax and MEKK1 leading to enhanced IKKbeta phosphorylation of IkappaB alpha.
核因子κB是细胞炎症和免疫反应的关键调节因子，可被人嗜T淋巴细胞病毒I型（HTLV-I）的转化和反式激活蛋白Tax激活。我们发现，Tax与IκB激酶复合体的组成成分蛋白激酶MEKK1的氨基末端结合，并刺激MEKK1激酶活性。Tax的表达增加了IκB激酶β（IKKβ）的活性，从而增强IκBα中丝氨酸残基的磷酸化，导致其降解。IKKβ和MEKK1的显性负性突变体可阻止Tax对NF-κB信号通路的激活。此外，重组MEKK1可刺激IKKβ对IκBα的磷酸化。因此，Tax介导的NF-κB核转位增加是由于Tax与MEKK1的直接相互作用导致IκBα的IKKβ磷酸化增强所致。
