Nemo-like kinase (NLK) negatively regulates NF-kappa B activity through disrupting the interaction of TAK1 with IKK?.

ABSTRACT: Stringent negative regulation of the transcription factor NF-?B is essential for maintaining cellular stress responses and homeostasis. However, the tight regulation mechanisms of IKK? are still not clear. Here, we reported that nemo-like kinase (NLK) is a suppressor of tumor necrosis factor (TNF?)-induced NF-?B signaling by inhibiting the phosphorylation of IKK?. Overexpression of NLK largely blocked TNF?-induced NF-?B activation, p65 nuclear localization and I?B? degradation; whereas genetic inactivation of NLK showed opposing results. Mechanistically, we identified that NLK interacted with I?B kinase (IKK)-associated complex, which in turn inhibited the assembly of the TAK1/IKK? and thereby, diminished the I?B kinase phosphorylation. Our results indicate that NLK functions as a pivotal negative regulator in TNF?-induced activation of NF-?B via disrupting the interaction of TAK1 with IKK?.

SUBMITTER: Li SZ 

PROVIDER: S-EPMC4655877 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature