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

Yeo, K.S. and Tan, M.C. and Wong, W.Y. and Loh, S.W. and Lam, Y.L. and Tan, C.L. and Lim, Y.Y. and Ea, C.K. (2016) JMJD8 is a positive regulator of TNF-induced NF-κB signaling. Scientific Reports, 6 (1). p. 34125. ISSN 2045-2322, DOI

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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.

Item Type: Article
Funders: University of Malaya High Impact Research Grant (UM.C/625/1/HIR/MOHE/CHAN/02) and Postgraduate Research Fund (PPP) (PG051-2014B)
Uncontrolled Keywords: JMJD8; Positive regulator; TNF-induced NF-κB; Signaling
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history
Divisions: Faculty of Science > Institute of Biological Sciences
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 31 May 2018 04:45
Last Modified: 31 May 2018 04:45

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