PMID:22028379

Citation	Ran, Y, Liu, TT, Zhou, Q, Li, S, Mao, AP, Li, Y, Liu, LJ, Cheng, JK and Shu, HB (2011) SENP2 negatively regulates cellular antiviral response by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation. J Mol Cell Biol 3:283-92
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.
Links	PubMed Online version:10.1093/jmcb/mjr020
Keywords	Animals; Cysteine Endopeptidases/genetics; Cysteine Endopeptidases/metabolism; Endopeptidases/genetics; Endopeptidases/metabolism; HEK293 Cells; Humans; Immunity, Innate/immunology; Interferon Regulatory Factor-3/genetics; Interferon Regulatory Factor-3/metabolism; Interferon-beta/metabolism; Mice; Mice, Knockout; Multienzyme Complexes/genetics; Multienzyme Complexes/metabolism; RNA Interference; Sendai virus/immunology; Signal Transduction/immunology; Small Ubiquitin-Related Modifier Proteins/metabolism; Sumoylation; Ubiquitination; Virus Replication
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:SENP2	involved_in	GO:0031397: negative regulation of protein ubiquitination	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SENP2	involved_in	GO:0031398: positive regulation of protein ubiquitination	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SENP2	involved_in	GO:0031648: protein destabilization	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SENP2	involved_in	GO:0016926: protein desumoylation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SENP2		GO:0016926: protein desumoylation	ECO:0000315:		P		Fig. 5A-C	complete CACAO 2615
HUMAN:SENP2		GO:0031648: protein destabilization	ECO:0000315:		P		Fig. 6B	complete CACAO 2616
HUMAN:SENP2		GO:0031398: positive regulation of protein ubiquitination	ECO:0000315:		P		Fig. 7(A-F) K48-Linked Ubiquitination	complete CACAO 2617
HUMAN:SENP2		GO:0031397: negative regulation of protein ubiquitination	ECO:0000314:		P		Supplementary Fig. S2A K63-Linked Ubiquitination	complete CACAO 2618
HUMAN:SENP2		GO:0050687: negative regulation of defense response to virus	ECO:0000315:		P		Fig. 1, Fig. 2, and Fig. 3	complete CACAO 2619

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