NDR1/STK38 potentiates NF-κB activation by its kinase activity.

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-κB activation. By overexpression, NDR1 potentiates NF-κB activation induced by TNFα, whereas knockdown of NDR1 expression inhibits NF-κB activation induced by TNFα. Coimmunoprecipitation shows that NDR1 interacts with multiple signal components except p65 in NF-κB signaling pathway. Furthermore, both phosphorylation and kinase dead mutants of NDR1 lose their synergistic effects on TNFα-induced NF-κB activation. siRNA oligo against NDR1 and kinase dead mutant as well mainly block the NF-κB 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-κB activation by its kinase activity.