Domain-specific interaction with the IκB kinase (IKK) regulatory subunit IKKγ is an essential step in tax-mediated activation of IKK
Domain-specific interaction with the IκB kinase (IKK) regulatory subunit IKKγ is an essential step in tax-mediated activation of IKK
复制标题
DOI：
10.1074/jbc.m002970200
复制
发表时间：
2000-11-03
影响因子：
4.8
通讯作者：
Sun, SC
中科院分区：
文献类型：
--
作者：
Xiao, GT;Harhaj, EW;Sun, SC
人类T细胞白血病病毒1型Tax癌蛋白通过持续刺激关键信号转导子I kappaB激酶（IKK）来解除NF-κ B信号通路的调节。Tax与IKK调节亚基IKK γ在物理上相关，尽管其潜在的生化机制和功能意义尚不清楚。我们发现，Tax-IKK γ相互作用需要两个位于IKK γ内的同源亮氨酸拉链域。这些亮氨酸拉链结构域对于Tax结合所必需的保守上游区域的存在是独特的。定点突变分析显示Tax的亮氨酸重复区对IKK γ结合很重要。有趣的是，所有IKK γ结合缺陷的Tax突变体都未能参与IKK复合物或刺激IKK活性，并且这些功能缺陷可以通过将Tax突变体融合到IKK γ来挽救。这些结果提供了Tax如何特异性靶向并功能性激活细胞激酶IKK的机制见解。
The human T-cell leukemia virus type 1 Tax oncoprotein deregulates the NF-kappaB signaling pathway by persistently stimulating a key signal transducer, the I kappaB kinase (IKK). Tax physically associates with the IKK regulatory subunit, IKK gamma, although the underlying biochemical mechanism and functional significance remain unclear. We show that the Tax-IKK gamma interaction requires two homologous leucine zipper domains located within IKK gamma. These leucine zipper domains are unique for the presence of a conserved upstream region that is essential for Tax binding. Site-directed mutagenesis analysis revealed that a leucine-repeat region of Tax is important for IKK gamma binding. Interestingly, all the Tax mutants defective in IKK gamma binding failed to engage the IKK complex or stimulate IKK activity, and these functional defects can be rescued by fusing the Tax mutants to IKK gamma These results provide mechanistic insights into how Tax specifically targets and functionally activates the cellular kinase IKK.