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.
Department of Immunology, School of Basic Medical Sciences, Key Laboratory of Medical Immunology-Ministry of Health, Peking University Health Science Center, Beijing, China.
Dan-Dan
DD
Shi
Hu
H
Shi
Dan
D
Lu
Rui
R
Li
Yu
Y
Zhang
Jun
J
Zhang
D015153:Blotting, Western; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016328:NF-kappa B; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; C491614:STK38 protein, human