NDR1/STK38 potentiates NF-?B activation by its kinase activity
NDR1/STK38 potentiates NF-?B activation by its kinase activity
复制标题
DOI：
10.1002/cbf.2846
复制
发表时间：
2012-12-01
影响因子：
3.6
通讯作者：
Zhang, Jun
中科院分区：
文献类型：
--
作者：
Shi, Dan-Dan;Shi, Hu;Zhang, Jun
人 NDR1/STK38 属于 Ser/Thr 激酶的核 Dbf2 相关 (NDR) 家族。它与中心体复制、细胞周期控制和细胞凋亡有关。然而，NDR1信号通路的机制在很大程度上仍不清楚。在这里，我们报告了 NDR1 在 NF-kappa B 激活中的新作用。通过过表达，NDR1 增强 TNF α 诱导的 NF-κ B 激活，而 NDR1 表达的敲低则抑制 TNF α 诱导的 NF-κ B 激活。免疫共沉淀显示，NDR1 与 NF-kappa B 信号通路中除 p65 之外的多个信号成分相互作用。此外，NDR1 的磷酸化和激酶死亡突变体都失去了对 TNF α 诱导的 NF-κ B 激活的协同作用。针对 NDR1 和激酶死亡突变体的 siRNA 寡核苷酸也主要阻断由 TRAF2 而不是 RIP1 诱导的 NF-κ B 激活。此外，NDR1 的激酶死亡突变体无法与 TRAF2 相互作用。综上所述，我们的研究结果表明 NDR1 的功能未知，可能通过其激酶活性调节 NF-κ B 激活。版权所有 (c) 2012 John Wiley & Sons, Ltd.
Human NDR1/STK38 belongs to the nuclear-Dbf2-related (NDR) family of Ser/Thr kinases. It has been implicated to function in centrosome duplication, control of cell cycle and apoptosis. However, the mechanism of NDR1 signaling pathway remains largely elusive. Here, we report a novel role of NDR1 in NF-kappa B activation. By overexpression, NDR1 potentiates NF-kappa B activation induced by TNF alpha whereas knockdown of NDR1 expression inhibits NF-kappa B activation induced by TNF alpha. Coimmunoprecipitation shows that NDR1 interacts with multiple signal components except p65 in NF-kappa B signaling pathway. Furthermore, both phosphorylation and kinase dead mutants of NDR1 lose their synergistic effects on TNF alpha-induced NF-kappa B activation. siRNA oligo against NDR1 and kinase dead mutant as well mainly block the NF-kappa B activation induced by TRAF2 but not RIP1. Furthermore, kinase dead mutant of NDR1 fails to interact with TRAF2. Taken together, our findings suggest an unknown function of NDR1, which may regulate NF-kappa B activation by its kinase activity. Copyright (c) 2012 John Wiley & Sons, Ltd.