Downregulation of diacylglycerol kinase ζ enhances activation of cytokine-induced NF-κB signaling pathway

The transcription factor NF-kappa B family serves as a key component of many pathophysiological events such as innate and adaptive immune response, inflammation, apoptosis, and oncogenesis. Various cell signals trigger activation of the regulatory mechanisms of NF-kappa B, resulting in its nuclear translocation and transcriptional initiation. The diacylglycerol kinase (DGK) family, a lipid second messenger-metabolizing enzyme in phosphoinositide signaling, is shown to regulate widely various cellular processes. Results of recent studies suggest that one family member, DGK zeta, is closely involved in immune and inflammatory responses. Nevertheless, little is known about the regulatory mechanism of DGK zeta on NF-kappa B pathway in cytokine-induced inflammatory signaling. This study shows that siRNA-mediated DGK zeta knockdown in HeLa cells facilitates degradation of I kappa B, followed by nuclear translocation of NF-kappa B p65 subunit. In addition, DGK zeta-deficient MEFs show upregulation of p65 subunit phosphoiylation at Serine 468 and 536 and its interaction with CBP transcriptional coactivator upon TNF-alpha stimulation. These modifications of p65 subunit might engender enhanced NF-kappa B transcriptional reporter assay of DGK zeta knockdown cells. These findings provide further insight into the regulatory mechanisms of cytokine-induced NF-kappa B activation. (C) 2014 Elsevier B.V. All rights reserved.