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 SZ, Zhang HH, Liang JB, Song Y, Jin BX, Xing NN, Fan GC, Du RL, and Zhang XD
- Subjects
- Cell Nucleus drug effects, Cell Nucleus metabolism, Gene Expression Regulation, HCT116 Cells, HEK293 Cells, Humans, I-kappa B Kinase genetics, Intracellular Signaling Peptides and Proteins antagonists & inhibitors, Intracellular Signaling Peptides and Proteins genetics, MAP Kinase Kinase Kinases genetics, NF-kappa B genetics, Phosphorylation drug effects, Protein Binding, Protein Serine-Threonine Kinases antagonists & inhibitors, Protein Serine-Threonine Kinases genetics, Proteolysis, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Signal Transduction, Tumor Necrosis Factor-alpha pharmacology, I-kappa B Kinase metabolism, Intracellular Signaling Peptides and Proteins metabolism, MAP Kinase Kinase Kinases metabolism, NF-kappa B metabolism, Protein Serine-Threonine Kinases metabolism
- 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 © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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