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SENP2 negatively regulates cellular antiviral response by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation.
- Source :
-
Journal of molecular cell biology [J Mol Cell Biol] 2011 Oct; Vol. 3 (5), pp. 283-92. - Publication Year :
- 2011
-
Abstract
- Transcription factor IRF3-mediated type I interferon induction is essential for antiviral innate immunity. We identified the deSUMOylating enzyme Sentrin/SUMO-specific protease  (SENP) 2 as a negative regulator of virus-triggered IFN-β induction. Overexpression of SENP2 caused IRF3 deSUMOylation, K48-linked ubiquitination, and degradation, whereas depletion of SENP2 had opposite effects. Both the SUMOylation and K48-linked ubiquitination of IRF3 occurred at lysines 70 and 87, and these processes are competitive. The level of virus-triggered IFN-β was markedly up-regulated and viral replication was reduced in SENP2-deficient cells comparing with wild-type controls. Our findings suggest that SENP2 regulates antiviral innate immunity by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation, and provide an example of cross-talk between the ubiquitin and SUMO pathways in innate immunity.
- Subjects :
- Animals
Cysteine Endopeptidases genetics
Endopeptidases genetics
Endopeptidases metabolism
HEK293 Cells
Humans
Interferon Regulatory Factor-3 genetics
Interferon-beta metabolism
Mice
Mice, Knockout
Multienzyme Complexes genetics
RNA Interference
Signal Transduction immunology
Sumoylation
Ubiquitination
Virus Replication
Cysteine Endopeptidases metabolism
Immunity, Innate immunology
Interferon Regulatory Factor-3 metabolism
Multienzyme Complexes metabolism
Sendai virus immunology
Small Ubiquitin-Related Modifier Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1759-4685
- Volume :
- 3
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of molecular cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 22028379
- Full Text :
- https://doi.org/10.1093/jmcb/mjr020