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Nemo-like kinase (NLK) negatively regulates NF-kappa B activity through disrupting the interaction of TAK1 with IKKβ.
- Source :
-
BBA - Molecular Cell Research . Jul2014, Vol. 1843 Issue 7, p1365-1372. 8p. - Publication Year :
- 2014
-
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]
Details
- Language :
- English
- ISSN :
- 01674889
- Volume :
- 1843
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- BBA - Molecular Cell Research
- Publication Type :
- Academic Journal
- Accession number :
- 95926192
- Full Text :
- https://doi.org/10.1016/j.bbamcr.2014.03.028