The nuclear factor kappa B (NF-kappa B) 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-kappa B in inflammation and immune-related signaling has been extensively studied. However, not much is known on the role of PKC in NF-kappa B regulation in response to DNA damage. Here we demonstrate for the first time that PKC-eta (PKC eta) regulates NF-kappa B upstream signaling by activating the I kappa B kinase (IKK) and the degradation of I kappa B. Furthermore, PKC eta enhances the nuclear translocation and transactivation of NF-kappa B under non-stressed conditions and in response to the anticancer drug camptothecin. We and others have previously shown that PKC eta confers protection against DNA damage-induced apoptosis. Our present study suggests that PKC eta is involved in NF-kappa B signaling leading to drug resistance. (C) 2011 Elsevier Inc. All rights reserved.