We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Epstein-Barr virus latent membrane protein-1 triggers AP-1 activity via the c-Jun N-terminal kinase cascade.
- Authors
Kieser, Arnd; Kilger, Ellen; Gires, Olivier; Ueffing, Marius; Kolch, Walter; Hammerschmidt, Wolfgang
- Abstract
The Epstein—Barr virus latent membrane protein-1 (LMP-1) is an integral membrane protein which transforms fibroblasts and is essential for EBV-mediated B-cell immortalization. LMP-1 has been shown to trigger cellular NF-κB activity which, however, cannot fully explain the oncogenic potential of LMP-1. Here we show that LMP-1 induces the activity of the AP-1 transcription factor, a dimer of Jun/Jun or Jun/Fos proteins. LMP-1 effects on AP-1 are mediated through activation of the c-Jun N-terminal kinase (JNK) cascade, but not the extracellular signal-regulated kinase (Erk) pathway. Consequently, LMP-1 triggers the activity of the c-Jun N-terminal transactivation domain which is known to be activated upon JNK-mediated phosphorylation. Deletion analysis indicates that the 55 C-terminal amino acids of the LMP-1 molecule, but not its TRAF interaction domain, are essential for AP-1 activation. JNK-mediated transcriptional activation of AP-1 is the direct output of LMP-1-triggered signaling, as shown by an inducible LMP-1 mutant. Using a tetracycline-regulated LMP-1 allele, we demonstrate that JNK is also an effector of non-cytotoxic LMP-1 signaling in B cells, the physiological target cells of EBV. In summary, our data reveal a novel effector of LMP-1, the SEK/JNK/c-Jun/AP-1 pathway, which contributes to our understanding of the immortalizing and transforming potential of LMP-1.
- Subjects
EPSTEIN-Barr virus; MEMBRANE proteins; CELLULAR signal transduction; TRANSCRIPTION factors; AMINO acids; B cells
- Publication
EMBO Journal, 1997, Vol 16, Issue 21, p6478
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/16.21.6478