Inflammasome activation controlled by the interplay between post-translational modifications: emerging drug target opportunities

Table 1 E3 ligases involved in ubiquitination of NLRP3 inflammasome components

E3 ligase	Activator	Substrate	Ubiquitylation site^a	Molecular or cellular outcome	Linkage specificity	Refs.
FBXL2	LPS	NLRP3	K689	NLRP3 degradation	unknown	[7]
TRIM31	LPS/IL-1β	NLRP3	NACHT domain	NLRP3 degradation	K48-linked	[20]
MARCH7	Dopamine	NLRP3	LRR domain	NLRP3 degradation	K48-linked	[21]
CUL1	LPS	NLRP3	K689	NLRP3 ubiquitination/negative regulation	K63-linked	[23]
CBLB	LPS/ATP	NLRP3	K496	NLRP3 degradation	K48-linked	[19]
RNF125	LPS	NLRP3	LRR domain	NLRP3 degradation	K63-linked	[19]
ARIH2	LPS/ATP/Nigericin	NLRP3	NACHT domain	NLRP3 ubiquitination/negative regulation	K48/K63-linked	[22]
Pellino2	LPS	Unknown	Unknown	NLRP3 ubiquitination/positive regulation	K63-linked	[24]
TRAF6	Pam3csk4	Unknown	Unknown	NLRP3 oligomerization/positive regulation	unknown	[25]
HOIL-1L (LUBAC)	LPS	ASC	PYD domain	ASC linear ubiquitination/positive regulation	M1-linked	[34]
TRAF3	VSV^b	ASC	K174	ASC ubiquitination/positive regulation	K63-linked	[33]
cIAP1/cIAP2/TRAF2	LPS	CASP1	unknown	CASP1 ubiquitination/positive regulation	K63-linked	[46]

^aAmino acid residues shown above refer to human NLRP3, those in brackets refer to mouse NLRP3 residues
^bVSV, vesicular stomatitis virus

ISSN: 1478-811X