Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Characterization of intercellular adhesion molecule-1 regulation by Epstein-Barr virus-encoded latent membrane protein-1 identifies pathways that cooperate with nuclear factor κB to activate transcription

Mehl, Anja M., Floettmann, J. Eike, Jones, Matthew, Brennan, Paul and Rowe, Martin 2001. Characterization of intercellular adhesion molecule-1 regulation by Epstein-Barr virus-encoded latent membrane protein-1 identifies pathways that cooperate with nuclear factor κB to activate transcription. Journal of Biological Chemistry 276 (2) , pp. 984-992. 10.1074/jbc.M003758200

Full text not available from this repository.

Abstract

The latent membrane protein-1 (LMP1) of Epstein-Barr virus induces gene transcription, phenotypic changes, and oncogenic transformation. One cellular gene induced by LMP1 is that for intercellular adhesion molecule-1 (ICAM-1), which participates in a wide range of inflammatory and immune responses. ICAM-1 may enhance the immune recognition of cells transformed by Epstein-Barr virus, and thus combat development of malignancy. Despite growing understanding of the various signaling functions of LMP1, the molecular mechanisms by which LMP1 induces ICAM-1 are not understood. Here, we demonstrate that transcriptional activation by LMP1 is absolutely dependent upon a variant NF-κB motif within the tumor necrosis factor α (TNFα) response element of the ICAM-1 promoter. Although the TNFα response element is sufficient for TNFα induction of the ICAM-1 promoter, LMP1 also required the cooperation of additional upstream sequences for optimal induction. Inhibitor studies of known LMP1-induced signaling pathways ruled out the involvement of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase, and the Janus-activating tyrosine kinase 3 (JAK3), and confirmed NF-κB as a critical factor for induction of ICAM-1. However, although constitutive activation of NF-κB efficiently induced promoter activity, it was not sufficient to induce either ICAM-1 mRNA or ICAM-1 protein. Using signaling defective LMP1 mutants and deacetylation inhibitors, we showed that the C-terminal activator region 1 of LMP1 delivers a new cooperating signal to induce ICAM-1 mRNA.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
ISSN: 00219258
Last Modified: 04 Jun 2017 06:12
URI: http://orca-mwe.cf.ac.uk/id/eprint/57199

Citation Data

Cited 32 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item