Identification of TRIM23 as a cofactor involved in the regulation of NF-kappaB by human cytomegalovirus.
Human cytomegalovirus (HCMV) regulates NF-kappaB during infection by a variety of mechanisms. For example, the HCMV gene product, UL144, is known to activate NF-kappaB in a tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)-dependent manner, causing the upregulation of the chemokine CCL22 (MDC). Viral UL144 is expressed from the UL/b' region of the HCMV genome at early times postinfection and is a TNFR1-like homologue. Despite this homology to the TNFR1 receptor superfamily, UL144 does not bind to members of the TNF ligand superfamily. We show here that the upregulation of NF-kappaB by UL144 is dependent upon cellular tripartite motif 23 (TRIM23) protein. We propose a mechanism by which UL144 activates NF-kappaB through a direct interaction with the cellular protein TRIM23 in a complex containing TRAF6. In contrast, TRIM23 is not involved in conventional double-stranded RNA signaling via NF-kappaB. Therefore, we present a novel role for TRIM23 that is specific to UL144-mediated activation of NF-kappaB during the course of virus infection.
Poole
Emma
E
Department of Medicine, University of Cambridge, Box 157, Level 5, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom.
Groves
Ian
I
MacDonald
Andrew
A
Pang
Yin
Y
Alcami
Antonio
A
Sinclair
John
J
D002460:Cell Line; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology* / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis*; D011485:Protein Binding; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*
D008562:Membrane Glycoproteins; D016328:NF-kappa B; D048029:TNF Receptor-Associated Factor 6; C080681:TRIM23 protein, human; C119624:UL144 ORF protein, Human herpesvirus 5; D014764:Viral Proteins; D019204:GTP-Binding Proteins