Xiangning ZhangDuangmanee SanmunLi Fu HuBengt FadeelIngemar ErnbergKarolinska University HospitalKarolinska InstitutetMahidol University2018-08-242018-08-242007-08-17Biochemical and Biophysical Research Communications. Vol.360, No.1 (2007), 263-268109021040006291X2-s2.0-34250849054https://repository.li.mahidol.ac.th/handle/20.500.14594/24140Our previous studies have shown that Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) potentiates chemotherapeutic agent-induced apoptosis in human cell lines of epithelial origin: cervical carcinoma-derived HeLa cells and nasopharyngeal carcinoma-derived TW03 cells. LMP1 acted upstream of caspase-dependent mitochondrial perturbation, and the effect was mapped to the C-terminal signaling domain of LMP1, designated CTAR2. CTAR2 is known to engage the c-Jun N-terminal kinase (JNK) and NF-κB pathways, and we show here that SP600125, a selective JNK inhibitor, suppresses LMP1 potentiation of cisplatin-induced mitochondrial damage and caspase activation in HeLa cells. Moreover, the potentiation of cisplatin-triggered caspase activation was blocked by Bay11-7082, a potent inhibitor of NF-κB. Similar results were obtained when a dominant negative form of IκB, a specific repressor of NF-κB, was co-expressed with LMP1. The current data support the notion that LMP1 modifies stress-induced apoptosis in epithelial cells through molecular interactions downstream of its C-terminal signaling domain. © 2007 Elsevier Inc. All rights reserved.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1016/j.bbrc.2007.06.043