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 cytomegalovirus, Human alphaherpesvirus 2
Compartment
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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

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

Nat. Immunol. 2012
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