| First Author | Rajsbaum R | Year | 2014 |
| Journal | Immunity | Volume | 40 |
| Issue | 6 | Pages | 880-95 |
| PubMed ID | 24882218 | Mgi Jnum | J:222665 |
| Mgi Id | MGI:5645191 | Doi | 10.1016/j.immuni.2014.04.018 |
| Citation | Rajsbaum R, et al. (2014) Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKepsilon kinase-mediated antiviral response. Immunity 40(6):880-95 |
| abstractText | 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 IkappaB kinase epsilon (IKKepsilon). However, the mechanism of IKKepsilon 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 IKKepsilon and promoted induction of IKKepsilon-dependent ISGs. TRIM6 and the E2-ubiquitin conjugase UbE2K cooperated in the synthesis of unanchored K48-linked polyubiquitin chains, which activated IKKepsilon 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. |
