title: Epstein-Barr virus oncoprotein LMP1 mediates survivin upregulation by             p53 contributing to G1/S cell cycle progression in nasopharyngeal carcinoma.
abstract: Latent membrane protein 1 (LMP1) is an important oncogenic protein encoded             by Epstein-Barr virus (EBV) and plays an important role in the development of             nasopharyngeal carcinoma (NPC). Our previous study has shown that p53 protein             was accumulated and phosphorylated in NPC, implying its transcription factor activity             in NPC tumorigenesis. However, the biological function and potential downstream             target of p53 mediated by LMP1 in NPC remain unknown. In this study, we found             that LMP1 simultaneously induced upregulation of both p53 and survivin at the             protein level, as well as their phosphorylation. Knockdown of p53 by siRNA revealed             that LMP1 increased survivin expression by p53 directly. Furthermore, we found             that LMP1 upregulated survivin by p53 at the transcriptional level by increasing             p53-mediated survivin promoter activity and DNA binding activity. Moreover, LMP1             induced the co-localization of p53 and survivin in the nucleus, conferring to             their related functions in NPC tumorigenesis. We further found that p53 promoted             G1/S cell cycle progression, but did not induce apoptosis in LMP1-positive NPC             cells. Collectively, these findings suggest that p53 acting as a transcription             factor promotes the transcriptional activity of survivin, and further increases             its protein expression and phosphorylation in the regulation of LMP1, thus, leading             to G1/S cell cycle progression with no effect on apoptosis in NPC tumorigenesis.
authors.affiliation: Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Guo
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.forename: Lifang
authors.initials: L
authors.lastname: Yang
authors.forename: Lanbo
authors.initials: L
authors.lastname: Xiao
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
authors.forename: Ya
authors.initials: Y
authors.lastname: Cao
mesh_terms: D017209:Apoptosis; D002277:Carcinoma; D002455:Cell Division; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000821:virology; D010766:Phosphorylation; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C107489:BIRC5 protein, human; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D014763:Viral Matrix Proteins