Type

Journal Article

Authors

Caroline A Jefferies
Christine A. Byron
Sally Ann Cryan
Rowan Higgs
Lara E. Kallai
Joan Ní Gabhann
Eoghan M. Mc.Carthy
Siobhán Smith
Elisa Lazzari
Claire Wynne
and 1 others

Subjects

Microbiology

Topics
production medical sciences toll like receptor type i immunology nf kb immune response detection

TRIM68 Negatively Regulates IFN-b Production by Degrading TRK Fused Gene, a Novel Driver of IFN-b Downstream of Anti-Viral Detection Systems (2014)

Abstract In recent years members of the tripartite motif-containing (TRIM) family of E3 ubiquitin ligases have been shown to both positively and negatively regulate viral defence and as such are emerging as compelling targets for modulating the anti-viral immune response. In this study we identify TRIM68, a close homologue of TRIM21, as a novel regulator of Toll-like receptor (TLR)- and RIG-I-like receptor (RLR)-driven type I IFN production. Proteomic analysis of TRIM68-containing complexes identified TRK-fused gene (TFG) as a potential TRIM68 target. Overexpression of TRIM68 and TFG confirmed their ability to associate, with TLR3 stimulation appearing to enhance the interaction. TFG is a known activator of NF-kB via its ability to interact with inhibitor of NF-kB kinase subunit gamma (IKK-c) and TRAF family member-associated NF-kB activator (TANK). Our data identifies a novel role for TFG as a positive regulator of type I IFN production and suggests that TRIM68 targets TFG for lysosomal degradation, thus turning off TFG-mediated IFN-b production. Knockdown of TRIM68 in primary human monocytes resulted in enhanced levels of type I IFN and TFG following poly(I:C) treatment. Thus TRIM68 targets TFG, a novel regulator of IFN production, and in doing so turns off and limits type I IFN production in response to anti-viral detection systems.
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Full list of authors on original publication

Caroline A Jefferies, Christine A. Byron, Sally Ann Cryan, Rowan Higgs, Lara E. Kallai, Joan Ní Gabhann, Eoghan M. Mc.Carthy, Siobhán Smith, Elisa Lazzari, Claire Wynne and 1 others

Experts in our system

1
Caroline A Jefferies
Royal College of Surgeons in Ireland
Total Publications: 50
 
2
Sally-Ann Cryan
Royal College of Surgeons in Ireland
Total Publications: 70
 
3
Joan Ní Gabhann
Royal College of Surgeons in Ireland
Total Publications: 23
 
4
Siobhán Smith
Royal College of Surgeons in Ireland
Total Publications: 19