NLRP4 and DTX4 associate with p-S172-TBK1 within dsDNA:ZBP1:TBK1

Stable Identifier
R-HSA-8948703
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human alphaherpesvirus 2, Human cytomegalovirus
Compartment
ReviewStatus
5/5
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NLRP4 (or NACHT, LRR and PYD domains-containing protein 4) and E3 ubiquitin-protein ligase DTX4 were reported to regulate the activation of type I interferon induced by double-stranded RNA or DNA (Cui J et al. 2012). Co-transfection with various combinations of full-length and truncated NLRP4 and DTX4 proteins in human embryonic kidney HEK293T cells, followed by IFN-signaling reporter assays and immunoassays showed that Nod domain of NLRP4 regulated TBK1 activity by recruiting DTX4 through the RING domain to the kinase domain of TBK1. The E3-ligase activity of DTX4 promoted K48-linked ubiquitination of TBK1 targeting it to the proteosomal degradation.The NLRP4 and DTX4 knockdown by siRNA in peripheral blood mononuclear cells (PBMCs) and THP-1 cells resulted in higher type I interferon production following stimulation with vesicular stomatitis virus (VSV), Sendai virus, and transfected Poly(dA:dT), which may engage various cytosolic receptors to activate IFN regulatory factor 3 (IRF3) downstream of TBK1 (Cui J et al. 2012).
Literature References
PubMed ID Title Journal Year
22388039 NLRP4 negatively regulates type I interferon signaling by targeting the kinase TBK1 for degradation via the ubiquitin ligase DTX4

Wang, HY, Cui, J, Songyang, Z, Li, Y, Wang, RF, Liu, D, Zhu, L

Nat. Immunol. 2012
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