Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery

Table 1 Linearly ubiquitinated proteins and their functional roles

Gene	Ubiquitination site	Linear ubiquitination function	Ref
AGO2	K820	Interfering miRNA-targeted mRNA recruiting to AGO2	[69]
ALK1	K210, K229, K440, K491	Inhibiting ALK1 enzyme activity and Smad1/5 activation	[70]
BCL10	K17, K31, K63	Recruiting NEMO to activate IKK and NF-κB	[71]
CASP8	Not determined (n.d)	Probably required for TRAIL-induced NF-κB activation	[41]
cFLIP	K351, K353	Protecting cells from TNFα-induced apoptosis	[72]
IRAK1/2/4	n.d	Recruiting NEMO to activate IKK and NF-κB	[73, 74]
LKB1	n.d	Activating AMPK pathway to inhibit NLRP3 inflammasome response	[75]
MyD88	n.d	Recruiting NEMO to activate IKK and NF-κB	[73, 74]
NEMO	K285, K309	Required for TNFα- and IL1β-induced NF-κB activation	[11, 76]
PINK1	n.d	Stabilizing PINK1 protein and counteracting OTULIN activity	[68]
PTEN	K144, K197	Inhibiting PTEN phosphatase activity	[77]
RIPK1	n.d	Required for TNFα-induced NF-κB activation	[11, 41]
RIPK2	n.d	Augmenting NOD2-dependent proinflammatory signaling	[30]
STAT1	K511, K652	Inhibiting STAT1 binding to the type I IFN receptor IFNAR2	[78]
STAT3	K153, K161, K163, K199	Recruiting the phosphatase TC-PTP to STAT3 to reduce STAT3 activity	[79]
TNFR1	n.d	Probably required for NF-κB activation	[30]

ISSN: 1478-811X