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Published online 5 March 2001. doi:10.1083/jcb.152.5.1115
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© The Rockefeller University Press, 0021-9525/2001//1115 $5.00
The Journal of Cell Biology, Volume 152, Number 5, , 2001 1115-1122


Report

Equine Herpesvirus Protein E10 Induces Membrane Recruitment and Phosphorylation of Its Cellular Homologue, Bcl-10



Margot Thomea, Olivier Gaidea, Olivier Micheaua, Fabio Martinona, David Bonneta, Montserrat Gonzaleza, and Jürg Tschoppa

a Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, CH-1066 Epalinges, Switzerland
Institute of Biochemistry, University of Lausanne, Ch. des Boveresses 155, CH-1066 Epalinges, Switzerland.41-21-692-57-0541-21-692-57-37

margot.thomemiazza{at}ib.unil.ch

v-E10, a caspase recruitment domain (CARD)-containing gene product of equine herpesvirus 2, is the viral homologue of the bcl-10 protein whose gene was found to be translocated in mucosa-associated lymphoid tissue (MALT) lymphomas. v-E10 efficiently activates the c-jun NH2-terminal kinase (JNK), p38 stress kinase, and the nuclear factor (NF)-{kappa}B transcriptional pathway and interacts with its cellular homologue, bcl-10, via a CARD-mediated interaction. Here we demonstrate that v-E10 contains a COOH-terminal geranylgeranylation consensus site which is responsible for its plasma membrane localization. Expression of v-E10 induces hyperphosphorylation and redistribution of bcl-10 from the cytoplasm to the plasma membrane, a process which is dependent on the intactness of the v-E10 CARD motif. Both membrane localization and a functional CARD motif are important for v-E10–mediated NF-{kappa}B induction, but not for JNK activation, which instead requires a functional v-E10 binding site for tumor necrosis factor receptor–associated factor (TRAF)6. Moreover, v-E10–induced NF-{kappa}B activation is inhibited by a dominant negative version of the bcl-10 binding protein TRAF1, suggesting that v-E10–induced membrane recruitment of cellular bcl-10 induces constitutive TRAF-mediated NF-{kappa}B activation.

Key Words: herpesvirus • bcl-10 • CARD • NF-{kappa}B • TRAF



© 2001 The Rockefeller University Press

M. Thome and O. Gaide contributed equally to this work.

Abbreviations used in this paper: CARD, caspase recruitment domain; EBV, Epstein-Barr virus; EHV, equine herpesvirus; JNK, c-jun NH2-terminal kinase; LMP, latent membrane protein; MALT, mucosa-associated lymphoid tissue; NF, nuclear factor; TRAF, tumor necrosis factor receptor–associated factor; VSV, vesicular stomatitis virus.



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