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The c-Jun N-terminal kinase pathway is critical for cell transformation by the latent membrane protein 1 of Epstein-Barr virus.

Virology 371, 246-256 (2008)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) transforms cells activating signal transduction pathways such as NF-kappaB, PI3-kinase, or c-Jun N-terminal kinase (JNK). Here, we investigated the functional role of the LMP1-induced JNK pathway in cell transformation. Expression of a novel dominant-negative JNK1 allele caused a block of proliferation in LMP1-transformed Rat1 fibroblasts. The JNK-specific inhibitor SP600125 reproduced this effect in Rat1-LMP1 cells and efficiently interfered with proliferation of EBV-transformed lymphoblastoid cells (LCLs). Inhibition of the LMP1-induced JNK pathway in LCLs caused the downregulation of c-Jun and Cdc2, the essential G2/M cell cycle kinase, which was accompanied by a cell cycle arrest of LCLs at G2/M phase transition. Moreover, SP600125 retarded tumor growth of LCLs in a xenograft model in SCID mice. Our data support a critical role of the LMP1-induced JNK pathway for proliferation of LMP1-transformed cells and characterize JNK as a potential target for intervention against EBV-induced malignancies.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Epstein–Barr virus (EBV); Latent membrane protein 1 (LMP1); c-Jun N-terminal kinase (JNK); JNK inhibitor; Transformation; Cell cycle; Tumor
ISSN (print) / ISBN 0042-6822
e-ISSN 0042-6822
Zeitschrift Virology
Quellenangaben Band: 371, Heft: 2, Seiten: 246-256 Artikelnummer: , Supplement: ,
Verlag Elsevier
Begutachtungsstatus Peer reviewed