Type

Other / n/a

Authors

Caroline A Jefferies
Christine A Biron
Sally-Ann Cryan
Rowan Higgs
Lara E Kallal
Joan Ní Gabhann
Eoghan M McCarthy
Siobhán Smith
Elisa Lazzari
Claire Wynne

Subjects

Biochemistry

Topics
controlled study transcription regulation proteomics tfg gene embryo gene identification life sciences gene targeting ubiquitination gene tgf gene monocyte promoter region gene overexpression human cell gene function lysosomal degradation cytokine production protein domain degradation down regulation protein function gene interaction protein protein interaction tlr3 gene human virus detection genetic association

TRIM68 negatively regulates IFN-β production by degrading TRK fused gene, a novel driver of IFN-β 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-κB via its ability to interact with inhibitor of NF-κB kinase subunit gamma (IKK-γ) and TRAF family member-associated NF-κB 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-β 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.
Collections Ireland -> Royal College of Surgeons in Ireland -> Department of Molecular and Cellular Therapeutics
Ireland -> Royal College of Surgeons in Ireland -> Molecular and Cellular Therapeutics Articles

Full list of authors on original publication

Caroline A Jefferies, Christine A Biron, Sally-Ann Cryan, Rowan Higgs, Lara E Kallal, Joan Ní Gabhann, Eoghan M McCarthy, Siobhán Smith, Elisa Lazzari, Claire Wynne

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
Eoghan McCarthy
Royal College of Surgeons in Ireland
Total Publications: 19
 
5
Siobhán Smith
Royal College of Surgeons in Ireland
Total Publications: 19