NF-kappaB-inducing kinase and IkappaB kinase participate in human T-cell leukemia virus I Tax-mediated NF-kappaB activation.
NF-kappaB-inducing kinase and IkappaB kinase participate in human T-cell leukemia virus I Tax-mediated NF-kappaB activation.
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发表时间：
1998
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通讯作者：
M. Uhlik;L. Good;G. Xiao;E. Harhaj;E. Zandi;M. Karin;S. Sun
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作者：
M. Uhlik;L. Good;G. Xiao;E. Harhaj;E. Zandi;M. Karin;S. Sun
人T细胞白血病病毒I的tax基因产物可诱导多种细胞基因的异常表达，从而有助于宿主细胞的转化。许多 Tax 靶基因的诱导是通过转录因子 NF-kappaB 介导的。在这里，我们发现 Tax 触发细胞蛋白激酶、IkappaB 激酶 α (IKKalpha) 和 IKKbeta 的激活，这些激酶使 NF-kappaB 抑制蛋白 IkappaB α 磷酸化，导致其降解和 NF-kappaB 激活。组成型 IKK 激活发生在 Tax 转染的 T 细胞和人 T 细胞白血病病毒 I 感染的 T 细胞中。我们进一步证明 Tax 介导的 NF-kappaB 信号传导也需要 NF-kappaB 诱导激酶 (NIK)。一致地，IKK 或 NIK 的非活性形式会减弱 Tax 介导的 NF-κB 激活。因此，Tax 通过靶向细胞信号分子（包括 IKK 和 NIK）来激活 NF-kappaB。
The tax gene product of human T-cell leukemia virus I induces aberrant expression of various cellular genes, which contributes to transformation of host cells. Induction of many Tax target genes is mediated through transcription factor NF-kappaB. Here we show that Tax triggers activation of cellular protein kinases, IkappaB kinase alpha (IKKalpha) and IKKbeta, which phosphorylate the NF-kappaB inhibitory protein IkappaB alpha, resulting in its degradation and NF-kappaB activation. Constitutive IKK activation occurs in both Tax-transfected and human T-cell leukemia virus I-infected T cells. We further demonstrate that Tax-mediated NF-kappaB signaling also requires the NF-kappaB-inducing kinase (NIK). Consistently, inactive forms of either IKKs or NIK attenuate Tax-mediated NF-kappaB activation. Therefore, Tax activates NF-kappaB by targeting cellular signaling molecules, including both IKKs and NIK.