The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3.
The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3.
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DOI：
10.4049/jimmunol.181.3.1780
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发表时间：
2008-08-01
期刊：
影响因子：
--
通讯作者：
Jefferies CA
中科院分区：
文献类型：
--
作者：
Higgs R;Ní Gabhann J;Ben Larbi N;Breen EP;Fitzgerald KA;Jefferies CA
Induction of type I interferons is a fundamental cellular response to both viral and bacterial infection. The role of the transcription factor IRF3 is well established in driving this process. However, equally as important are cellular mechanisms for turning off type I interferon production in order to limit this response. In this respect, IRF3 has previously been shown to be targeted for ubiquitin-mediated degradation post-viral detection in order to turn off the IFN-β response. Here we provide evidence that the E3 ligase Ro52 (TRIM21) targets IRF3 for degradation post-pathogen recognition receptor activation. We demonstrate that Ro52 interacts with IRF3 via its C-terminal SPRY domain, resulting in the polyubiquitination and proteasomal degradation of the transcription factor. Ro52-mediated IRF3 degradation significantly inhibits IFN-β promoter activity, an effect that is reversed in the presence of the proteasomal inhibitor MG132. Specific targeting of Ro52 using shRNA rescues IRF3 degradation following polyI:C-stimulation of HEK293T cells, with a subsequent increase in IFN-β production. Additionally, shRNA targeting of murine Ro52 enhances the production of the IRF3-dependent chemokine RANTES following Sendai virus infection of murine fibroblasts. Collectively, this demonstrates a novel role for Ro52 in turning off and thus limiting IRF3-dependent type I interferon production by targeting the transcription factor for polyubiquitination and subsequent proteasomal degradation.
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影响因子：
15.9
作者：
CHAN, EKL;HAMEL, JC;TAN, EM
通讯作者：
TAN, EM
DOI：
10.1073/pnas.2237236100
发表时间：
2004-01-06
影响因子：
11.1
作者：
McWhirter, SM;Fitzgerald, KA;Maniatis, T
通讯作者：
Maniatis, T
影响因子：
5.3
作者：
Huye, Leslie E.;Ning, Shunbin;Pagano, Joseph S.
通讯作者：
Pagano, Joseph S.
影响因子：
5.3
作者：
Lin, RT;Heylbroeck, C;Hiscott, J
通讯作者：
Hiscott, J
影响因子：
4.4
作者：
Kong, Hee Jeong;Anderson, D. Eric;Ozato, Keiko
通讯作者：
Ozato, Keiko