Latent membrane protein 1 encoded by Epstein-Barr virus induces telomerase activity via p16INK4A/Rb/E2F1 and JNK signaling pathways.
Elevated telomerase activity is observed in about 90% of human cancers. This activity correlates strictly with human telomerase reverse transcriptase (hTERT). Previously, it was shown that the Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) induced telomerase activity in nasopharyngeal carcinoma cells. In this study, it was indicated that LMP1 inhibited p16(INK4A) expression, promoted phosphorylation of p105 Rb and upregulated E2F1 expression as well as transactivation, and overexpression of E2F1 alone was sufficient to upregulate telomerase activity. The JNK kinase cascade could also promote telomerase activity modulated by LMP1, that inhibition of JNK by JIP and TAM 67 dominant negative mutant abrogated telomerase activity. The data show that p16(INK4A)/Rb/E2F1 and JNK signaling pathways are involved in the regulation of telomerase activity via LMP1. The present study provides new perspectives on carcinogenesis of nasopharyngeal carcinoma that may be exploited for novel therapeutic strategies.
Ding
Lin
L
Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Li
Lili
L
Yang
Jing
J
Zhou
Shanghui
S
Li
Wei
W
Tang
Min
M
Shi
Ying
Y
Yi
Wei
W
Cao
Ya
Y
D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015398:Signal Transduction; D019098:Telomerase / Q000378:metabolism*; D015533:Transcriptional Activation; D014763:Viral Matrix Proteins / Q000378:metabolism*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016160:Retinoblastoma Protein; D014763:Viral Matrix Proteins; D048670:MAP Kinase Kinase 4; D019098:Telomerase