Activation of anti-apoptotic gene transcription by NF-kappa B (nuclear factor-kappa B) has been reported to be linked with a resistance of cancer cells against chemotherapy. NEMO (NF-kappa B essential modulator) interacts with a number of proteins and modulates the activity of NF-kappa B pathway. In this study, we revealed that RPAP3 (RNA polymerase II-associated protein 3) possesses an activity to bind with NEMO and to inhibit the ubiquitination of NEMO and that RPAP3 enhances doxorubicin-induced cell death in breast cancer cell line T-47D through the marked impairment of NF-kappa B pathway. These results indicate that RPAP3 may be a novel modulator of NF-kappa B pathway in apoptosis induced by anti-cancer chemotherapeutic agents. (C) 2010 Elsevier Inc. All rights reserved.