The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, The Cancer Research Center, Ben-Gurion University of the Negev, Israel.
Biochem Biophys Res Commun. 2011 Aug 26;412(2):313-7. doi: 10.1016/j.bbrc.2011.07.090. Epub 2011 Jul 28.
The nuclear factor κB (NF-κB) family of transcription factors participates in the regulation of genes involved in innate- and adaptive-immune responses, cell death and inflammation. The involvement of the Protein kinase C (PKC) family in the regulation of NF-κB in inflammation and immune-related signaling has been extensively studied. However, not much is known on the role of PKC in NF-κB regulation in response to DNA damage. Here we demonstrate for the first time that PKC-eta (PKCη) regulates NF-κB upstream signaling by activating the IκB kinase (IKK) and the degradation of IκB. Furthermore, PKCη enhances the nuclear translocation and transactivation of NF-κB under non-stressed conditions and in response to the anticancer drug camptothecin. We and others have previously shown that PKCη confers protection against DNA damage-induced apoptosis. Our present study suggests that PKCη is involved in NF-κB signaling leading to drug resistance.
核因子 κB（NF-κB）转录因子家族参与调节固有免疫和适应性免疫反应、细胞死亡和炎症相关的基因。蛋白激酶 C（PKC）家族在炎症和免疫相关信号转导中对 NF-κB 的调节作用已得到广泛研究。然而，关于 PKC 在 NF-κB 对 DNA 损伤反应中的调节作用知之甚少。在这里，我们首次证明 PKC-eta（PKCη）通过激活 IκB 激酶（IKK）和 IκB 的降解来调节 NF-κB 的上游信号。此外，PKCη 在非应激条件下以及在抗癌药物喜树碱的作用下增强 NF-κB 的核转位和转录激活。我们和其他人之前已经表明 PKCη 可以对抗 DNA 损伤诱导的细胞凋亡。本研究表明 PKCη 参与 NF-κB 信号转导，导致耐药性。
