1. Nemo-like kinase (NLK) negatively regulates NF-kappa B activity through disrupting the interaction of TAK1 with IKKβ.
- Author
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Li, Shang-Ze, Zhang, Hui-Hui, Liang, Jun-Bo, Song, Yang, Jin, Bing-Xue, Xing, Na-Na, Fan, Guo-Chang, Du, Run-Lei, and Zhang, Xiao-Dong
- Subjects
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PROTEIN kinase regulation , *NF-kappa B , *TUMOR necrosis factors , *PHOSPHORYLATION , *TRANSCRIPTION factors , *GENE expression - Abstract
Abstract: Stringent negative regulation of the transcription factor NF-κB is essential for maintaining cellular stress responses and homeostasis. However, the tight regulation mechanisms of IKKβ are still not clear. Here, we reported that nemo-like kinase (NLK) is a suppressor of tumor necrosis factor (TNFα)-induced NF-κB signaling by inhibiting the phosphorylation of IKKβ. Overexpression of NLK largely blocked TNFα-induced NF-κB activation, p65 nuclear localization and IκBα degradation; whereas genetic inactivation of NLK showed opposing results. Mechanistically, we identified that NLK interacted with IκB kinase (IKK)-associated complex, which in turn inhibited the assembly of the TAK1/IKKβ and thereby, diminished the IκB kinase phosphorylation. Our results indicate that NLK functions as a pivotal negative regulator in TNFα-induced activation of NF-κB via disrupting the interaction of TAK1 with IKKβ. [Copyright &y& Elsevier]
- Published
- 2014
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