Nuclear factor-κB (NF-κB) is tightly modulated by IκB kinases and IκBα in the cytoplasm. On stimulation, NF-κB translocates into the nucleus to initiate transcription; however, regulation of its transcriptional activity remains obscure. Here, we show that protein kinase C (PKC) δ controls the main subunit of NF-κB, RelA/p65. On exposure to tumor necrosis factor-α (TNF-α), the expression of RelA/p65 target genes such as IκBα, RelB, and p100/p52 is upregulated in a PKCδ-dependent manner. The results also showthat PKCδ is targeted to the nucleus and forms a complex with RelA/p65 following TNF-α exposure. Importantly, kinase activity of PKCδ is required for RelA/p65 transactivation. In concert with these results, PKCδ activates RelA/p65 for its occupancy to target-gene promoters, including IκBα and p100/p52. Moreover, functional analyses showthat inhibition of PKCδ is associated with substantial attenuation of NF-κB activity in response to TNF-α. These findings provide evidence that PKCδ orchestrates RelA/p65 transactivation, a requisite for NF-κB signaling pathway in the nucleus. ©2009 American Association for Cancer Research.
Lu, Z. G., Liu, H., Yamaguchi, T., Miki, Y., & Yoshida, K. (2009). Protein kinase Cδ activates RelA/p65 and nuclear factor-κB signaling in response to tumor necrosis factor-α. Cancer Research, 69(14), 5927–5935. https://doi.org/10.1158/0008-5472.CAN-08-4786