Reactome | NLRC5 functions as negative regulator of the NF-kappa B sign...

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created	[InstanceEdit:9750951] Shamovsky, Veronica, 2021-08-17
dbId	9750952
displayName	NLRC5 functions as negative regulator of the NF-kappa B sign...
literatureReference	[LiteratureReference:937326] NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways [LiteratureReference:9750928] Reversible ubiquitination shapes NLRC5 function and modulates NF-?B activation switch
modified	[InstanceEdit:9757934] Shamovsky, Veronica, 2021-11-05
schemaClass	Summation
text	NLRC5 functions as negative regulator of the NF-kappa B signaling pathway by targeting the I-kappa-B-kinase (IKK) complex (Cui J et al. 2010). The IKK complex consists of two catalytic subunits, IKBKA (KK? or CHUK) and IKBKB (IKK?), associated with a regulatory subunit IKBKG (NEMO). NLRC5 directly binds to CHUK and IKBKB inhibiting their phosphorylation and interaction with IKBKG (Cui J et al. 2010). The dynamics of NLRC5 interaction with IKBKB/CHUK is regulated by TRAF2 or TRAF6-dependent K63-linked polyubiquitination of NLRC5 at K1178 (Meng Q et al. 2015). The ubiquitinated NLRC5 (K63-polyUb-NLRC5) showed lower ability to interact with IKBKB/CHUK thereby resulting in a decreased inhibitory function of NLRC5. Ubiquitin-specific protease 14 (USP14) was found to remove the polyUb chains from NLRC5 and thereby enhanced the NLRC5-mediated inhibition of NF-kB signaling (Meng Q et al. 2015).

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