JMJD8 is a positive regulator of TNF-induced NF-κB signaling

Kok Siong Yeo, Ming Cheang Tan, Wan Ying Wong, Sheng Wei Loh, Yi Lyn Lam, Chin Leng Tan, Yat Yuen Lim, Chee Kwee Ea

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7 Scopus citations

Abstract

TNF-induced signaling mediates pleiotropic biological consequences including inflammation, immunity, cell proliferation and apoptosis. Misregulation of TNF signaling has been attributed as a major cause of chronic inflammatory diseases and cancer. Jumonji domain-containing protein 8 (JMJD8) belongs to the JmjC family. However, only part of the family members has been described as hydroxylase enzymes that function as histone demethylases. Here, we report that JMJD8 positively regulates TNF-induced NF-κB signaling. Silencing the expression of JMJD8 using RNA interference (RNAi) greatly suppresses TNF-induced expression of several NF-κB-dependent genes. Furthermore, knockdown of JMJD8 expression reduces RIP ubiquitination, IKK kinase activity, delays IκBα degradation and subsequently blocks nuclear translocation of p65. In addition, JMJD8 deficiency enhances TNF-induced apoptosis. Taken together, these findings indicate that JMJD8 functions as a positive regulator of TNF-induced NF-κB signaling.

Original languageEnglish (US)
Article number34125
JournalScientific Reports
Volume6
DOIs
StatePublished - Sep 27 2016

ASJC Scopus subject areas

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    Yeo, K. S., Tan, M. C., Wong, W. Y., Loh, S. W., Lam, Y. L., Tan, C. L., Lim, Y. Y., & Ea, C. K. (2016). JMJD8 is a positive regulator of TNF-induced NF-κB signaling. Scientific Reports, 6, [34125]. https://doi.org/10.1038/srep34125