Type

Journal Article

Authors

Caroline A Jefferies
Betsy J Barnes
Siobhán Smith
Joan Ní Gabhann
Justyna Korczeniewska
Elisa Lazzari

Subjects

Biochemistry

Topics
protein binding immunoprecipitation microscopy confocal protein stability genetics interferon regulatory factors hela cells ribonucleoproteins cell line real time polymerase chain reaction protein isoforms humans metabolism irf5 protein human tlr7 protein human ss a antigen blotting western toll like receptor 7

TRIpartite motif 21 (TRIM21) differentially regulates the stability of interferon regulatory factor 5 (IRF5) isoforms. (2014)

Abstract IRF5 is a member of the Interferon Regulatory Factor (IRF) family of transcription factors activated downstream of the Toll-Like receptors (TLRs). Polymorphisms in IRF5 have been shown to be associated with the autoimmune disease Systemic Lupus Erythematosus (SLE) and other autoimmune conditions, suggesting a central role for IRF5 in the regulation of the immune response. Four different IRF5 isoforms originate due to alternative splicing and to the presence or absence of a 30 nucleotide insertion in IRF5 exon 6. Since the polymorphic region disturbs a PEST domain, a region associated with protein degradation, we hypothesized that the isoforms bearing the insertion might have increased stability, thus explaining the association of individual IRF5 isoforms with SLE. As the E3 ubiquitin ligase TRIpartite Motif 21 (TRIM21) has been shown to regulate the stability and hence activity of members of the IRF family, we investigated whether IRF5 is subjected to regulation by TRIM21 and whether dysregulation of this mechanism could explain the association of IRF5 with SLE. Our results show that IRF5 is degraded following TLR7 activation and that TRIM21 is involved in this process. Comparison of the individual IRF5 variants demonstrates that isoforms generated by alternative splicing are resistant to TRIM21-mediated degradation following TLR7 stimulation, thus providing a functional link between isoforms expression and stability/activity which contributes to explain the association of IRF5 with SLE.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Caroline A Jefferies, Betsy J Barnes, Siobhán Smith, Joan Ní Gabhann, Justyna Korczeniewska, Elisa Lazzari

Experts in our system

1
Caroline A Jefferies
Royal College of Surgeons in Ireland
Total Publications: 50
 
2
Siobhán Smith
Royal College of Surgeons in Ireland
Total Publications: 19
 
3
Joan Ní Gabhann
Royal College of Surgeons in Ireland
Total Publications: 23