Latent membrane protein 1 encoded by Epstein-Barr virus induces telomerase activity via p16INK4A/Rb/E2F1 and JNK signaling pathways

Lin Ding, Lili Li, Jing Yang, Shanghui Zhou, Wei Li, Min Tang, Ying Shi, Wei Yi, Ya Cao

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

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 mutantabrogatedtelomerase activity. The data show that p16INK4A/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.

Original languageEnglish (US)
Pages (from-to)1153-1163
Number of pages11
JournalJournal of Medical Virology
Volume79
Issue number8
DOIs
StatePublished - Aug 1 2007

Keywords

  • hTERT
  • JNK
  • Latent membrane protein 1
  • p16/Rb/E2F1
  • Telomerase

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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