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 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.
journal_name
J Med Viroljournal_title
Journal of medical virologyauthors
Ding L,Li L,Yang J,Zhou S,Li W,Tang M,Shi Y,Yi W,Cao Ydoi
10.1002/jmv.20896subject
Has Abstractpub_date
2007-08-01 00:00:00pages
1153-63issue
8eissn
0146-6615issn
1096-9071journal_volume
79pub_type
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