NF-kappa B p65 transactivation domain is involved in the NF-kappa B-inducing kinase pathway.
NF-kappa B p65 transactivation domain is involved in the NF-kappa B-inducing kinase pathway.
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DOI：
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发表时间：
2003
影响因子：
3.1
通讯作者：
Xu Jiang;N. Takahashi;K. Ando;T. Otsuka;T. Tetsuka;T. Okamoto
中科院分区：
文献类型：
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作者：
Xu Jiang;N. Takahashi;K. Ando;T. Otsuka;T. Tetsuka;T. Okamoto
NF-κ B 诱导激酶 (NIK) 参与导致 NF-κ B 激活的信号转导途径。在本报告中，我们证明 NIK 介导的 NF-κ B 激活涉及 NF-κ B p65 亚基的反式激活 (TA) 结构域和 IKK α 的核转位。通过使用荧光素酶测定，我们发现 IKK α 和 IKK β 都可以与 NIK 协同激活 NF-κ B。有趣的是，虽然 IKK beta 刺激 NIK 介导的 I kappa B 降解，但 IKK α 刺激 NF-kappa B 的作用，但不增强 I kappa B 降解。通过使用异源反式激活系统，Gal4 DNA 结合结构域与 p65 TA 结构域的各个部分融合，我们发现 p65 的反式激活结构域 1 (TA1) 作为 NIK-IKK α 级联的直接靶标，并且 p65 TA1 内 536 处的丝氨酸残基对于此作用是必不可少的。此外，我们发现NIK的这种作用取决于Ras相关蛋白（Ran）的能量依赖性作用，因为Ran的显性失活突变体（RanQ69L）通过阻止IKK α的核输入来抑制p65的转录活性。
NF-kappa B-inducing kinase (NIK) is involved in the signal transduction pathway leading to the NF-kappa B activation. In this report, we demonstrate that the NIK-mediated NF-kappa B activation involves the transactivation (TA) domain of p65 subunit of NF-kappa B and the nuclear translocation of IKK alpha. By using luciferase assay, we found that both IKK alpha and IKK beta could activate NF-kappa B in synergy with NIK. Interestingly, although IKK beta stimulated the NIK-mediated I kappa B degradation, IKK alpha stimulated the action of NF-kappa B without enhancing the I kappa B degradation. By using heterologous transactivation system with Gal4 DNA-binding domain in fusion with various portions of p65 TA domain, we found that the transactivation domain 1 (TA1) of p65 serves as the direct target for the NIK-IKK alpha cascade and that the serine residue at 536 within p65 TA1 is indispensable for this action. Furthermore, we found that this action of NIK depends on the energy-dependent action of Ras-related protein (Ran) since the dominant negative mutant of Ran (RanQ69L) inhibited the transcriptional activity of p65 by preventing the nuclear import of IKK alpha.