Back to Search
Start Over
Unanchored K48-Linked Polyubiquitin Synthesized by the E3-Ubiquitin Ligase TRIM6 Stimulates the Interferon-IKKε Kinase-Mediated Antiviral Response.
- Source :
-
Immunity (10747613) . Jun2014, Vol. 40 Issue 6, p880-895. 16p. - Publication Year :
- 2014
-
Abstract
- Summary: 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10747613
- Volume :
- 40
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Immunity (10747613)
- Publication Type :
- Academic Journal
- Accession number :
- 96662004
- Full Text :
- https://doi.org/10.1016/j.immuni.2014.04.018