PMID:21561061

Citation	Varshney, B and Lal, SK (2011) SARS-CoV accessory protein 3b induces AP-1 transcriptional activity through activation of JNK and ERK pathways. Biochemistry 50:5419-25
Abstract	The outbreak of severe acute respiratory syndrome (SARS) in 2003 in China, characterized by atypical pneumonia, was associated with the emergence of a novel coronavirus named severe acute respiratory syndrome coronavirus (SARS-CoV). Eight accessory proteins of SARS coronavirus were the suspected players in the pathogenesis of the virus. Among them, protein 3b localizes to the nucleus and behaves as an interferon antagonist by inhibiting IRF3 activation. However, the effect of 3b on the activity of other common host transcription factors remains unexplored. In this work, we studied the effect of 3b on the transcriptional activity of AP-1. Our findings elucidate augmentation of AP-1-dependent gene expression in 3b-transfected Huh7 cells. Reporter gene and mobility shift assays depict an increase in the AP-1 transcriptional and DNA binding activity in the presence of 3b. This increase in activity correlates with the activation of ERK and JNK pathways. Furthermore, 3b expression potentiates AP-1-driven promoter activity of proinflammatory cytokine MCP-1, suggesting a plausible role for 3b as a virulence factor that might function by upregulating AP-1-dependent cytokine levels in SARS-CoV infection.
Links	PubMed Online version:10.1021/bi200303r
Keywords	Animals; Base Sequence; Cell Line; Cercopithecus aethiops; Chemokine CCL2/genetics; DNA Probes/genetics; Humans; Interferon Regulatory Factor-3/metabolism; JNK Mitogen-Activated Protein Kinases/metabolism; MAP Kinase Signaling System; Promoter Regions, Genetic; Proto-Oncogene Proteins c-fos/metabolism; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; SARS Virus/genetics; SARS Virus/metabolism; SARS Virus/pathogenicity; Signal Transduction; Transcription Factor AP-1/metabolism; Transcriptional Activation; Transfection; Vero Cells; Viral Regulatory and Accessory Proteins/genetics; Viral Regulatory and Accessory Proteins/metabolism; Virulence
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
CVHSA:NS3B		GO:0001817 : regulation of cytokine production	ECO:0000270:		P		Protein 3b has been shown to trigger the ERK and JNK pathways which lead to an increase of AP-1 activity. AP-1 regulates transcription of cytokine MCP-1. Protein 3b is suggested to serve as a virulence factor for SARS-CoV. Figure 3, Figure 4, Figure 6.	complete CACAO 2304
CVHSA:NS3B	involved_in	GO:0001817: regulation of cytokine production	ECO:0000270: expression pattern evidence used in manual assertion		P		Seeded From UniProt	complete

References

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