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Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral response.

Authors :
Rajsbaum R
Versteeg GA
Schmid S
Maestre AM
Belicha-Villanueva A
Martínez-Romero C
Patel JR
Morrison J
Pisanelli G
Miorin L
Laurent-Rolle M
Moulton HM
Stein DA
Fernandez-Sesma A
tenOever BR
García-Sastre A
Source :
Immunity [Immunity] 2014 Jun 19; Vol. 40 (6), pp. 880-95. Date of Electronic Publication: 2014 May 29.
Publication Year :
2014

Abstract

Type I interferons (IFN-I) are essential antiviral cytokines produced upon microbial infection. IFN-I elicits this activity through the upregulation of hundreds of IFN-I-stimulated genes (ISGs). The full breadth of ISG induction demands activation of a number of cellular factors including the IκB kinase epsilon (IKKε). However, the mechanism of IKKε activation upon IFN receptor signaling has remained elusive. Here we show that TRIM6, a member of the E3-ubiquitin ligase tripartite motif (TRIM) family of proteins, interacted with IKKε and promoted induction of IKKε-dependent ISGs. TRIM6 and the E2-ubiquitin conjugase UbE2K cooperated in the synthesis of unanchored K48-linked polyubiquitin chains, which activated IKKε for subsequent STAT1 phosphorylation. Our work attributes a previously unrecognized activating role of K48-linked unanchored polyubiquitin chains in kinase activation and identifies the UbE2K-TRIM6-ubiquitin axis as critical for IFN signaling and antiviral response.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1097-4180
Volume :
40
Issue :
6
Database :
MEDLINE
Journal :
Immunity
Publication Type :
Academic Journal
Accession number :
24882218
Full Text :
https://doi.org/10.1016/j.immuni.2014.04.018