Abstract 1020: Latent membrane protein 1 N-C interaction of EBV facilitates (nuclear factor kappa-light-chain-enhancer of activated B cells transcriptional activity

Abstract

Abstract Background: Epstein-Barr virus latent membrane protein 1 (LMP1) is known to be involved in the carcinogenesis of numerous cancers, including nasopharyngeal carcinoma and lymphoma. The C-terminus of LMP1 can recruit a spectrum of host cell cytosolic signaling molecules to exert its effects on downstream pathways. However, the function of the cytosolic N-terminus of LMP1 is not clear. Methods: Partial deletion or point mutation of the N-terminus of LMP1 were made. Results: Sequence analysis showed that not only were the lengths of LMP1 N- and C-termini different, so too were their distributions of charged amino acid side chains, with negatively charged amino acids being abundant in the C-terminus and positively charged amino acids dominating in the N-terminus. We found that deletion or mutation of N-terminal positively charged amino acids weakened the effects of LMP1 on nuclear factor NF-κB transcriptional activity. Furthermore, co-expressing a short N-terminal peptide of LMP1 enhanced the effect of full-length LMP1 on NF-κB transcriptional activity. We further demonstrated that the LMP1 N- and C-termini interact, which facilitated downstream signal transduction. Mutation of N-termial positively charged side chain amino acid could weaken LMP1 effect on cell motility. Conclusion: LMP1 N- and C-termini could interact and facilitate NF-κB transcriptional activity and cell motility. Citation Format: Cheng-Lung Hsu, Hsin-Pai Li, Yung-Chia Kuo, Ngan-Ming Tsang, Yu-Sun Chang. Latent membrane protein 1 N-C interaction of EBV facilitates (nuclear factor kappa-light-chain-enhancer of activated B cells transcriptional activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1020. doi:10.1158/1538-7445.AM2015-1020