Table 3:

Examples of mutual regulation in the human DUB-E3 interaction network

DUB	E3	Regulatory function of complex	References
DUB-E3 interactions that promote the activity of the E3 ubiquitin ligase
CSN5	MDM2	CSN5 deubiquitylates MDM2, thereby regulating p53 stability	[87]
OTUB1	TRAF6	OTUB1 and OTUB2 interact with TRAF3 and TRAF6 to attenuate innate immune signaling	[57]
USP2	MDM2	USP2a regulates p53 by deubiquitylating and stabilizing MDM2	[59]
USP4	HUWE1	USP4 deubiquitylates HUWE1 resulting in decreased p53 levels	[88]
USP4	TRAF2	USP4 deubiquitylates TRAF2 to attenuate innate immune signaling	[55]
USP4	TRAF6	USP4 deubiquitylatesTRAF6 to attenuate innate immune signaling	[55] [56]
USP7	MARCH7	USP7 deubquitylates and stabilizes MARCH7 in the nucleus	[89]
USP7	MDM2	USP7 deubiquitylates MDM2 to promote its stability and destabilize p53	[90, 91]
USP7	RAD18	USP7 deubiquitylates RAD18 to regulate the DNA damage response	[92]
USP7	RNF168	USP7 deubiquitylates RNF168 to regulate the DNA damage response	[93]
USP7	RNF169	USP7 deubiquitylates RNF169 to promote double-strand break repair	[94]
USP7	TRIM27	USP7 deubiquitylates TRIM27 regulating WASH complex activation	[25]
USP7	UHRF1	USP7 interaction with UHRF1 promotes its association with chromatin	[95]
USP9X	ITCH	USP9X interacts with ITCH and antagonizes autoubiquitylation, promoting its stability	[96–98]
USP9X	MARCH7	USP9X deubquitylates and stabilizes MARCH7 in the cytosol	[89]
USP9X	SMURF1	USP9X interacts with SMURF and antagonizes autoubiquitylation, promoting its stability	[99]
USP10	TRAF6	USP10 interacts in a complex with TANK and MCPIP1 in order to deubiquitylate TRAF6 and attenuate NFκB activation	[100]
USP11	XIAP	USP11 deubiquitylates XIAP, promoting tumor initiation	[101]
USP12	MDM2	USP12 negatively regulates p53 stability by deubiquitylating MDM2	[61]
USP15	SMURF2	USP15 deubiquitylates SMURF2 to regulate TGFβ receptor signaling	[28, 102]
USP19	XIAP	USP19 regulates the stability of XIAP, enhancing TNFα-induced caspase activation and apoptosis	[103]
USP20	TRAF6	USP20 negatively regulates NFκB activation by deubiquitylating TRAF6	[58]
USP26	MDM2	USP26 deubiquitylates MDM2 resulting in decreased stability of p53	[60]
DUB-E3 interactions that destabilize the DUB by promoting proteasomal degradation
AMSH	SMURF2	RNF11 recruits AMSH to Smurf2 for ubiquitination, leading to its degradation by the 26S proteasome	[104]
UCHL1	PARK2	UCHL1 is ubiquitylated and degraded in a PARK2-dependent manner	[105]
USP5	SMURF1	USP5 is ubiquitylated and degraded in a USP5-dependent manner	[65]
USP20	VHL	USP20 is ubiquitylated and degraded in a pVHL-dependent manner	[106]
USP19	SIAH1/2	SIAH1 and SIAH2 promote USP19 ubiquitylation and proteasomal degradation	[107]
USP33	β-TrCP	USP33 is ubiquitylated and degraded in a β-TrCP-dependent manner	[108]
USP33	VHL	USP33 is ubiquitylated and degraded in a pVHL-dependent manner	[106]
USP37	βTrCP	SCFβTrCP ubiquitylates USP37 to promote its degradation and facilitate mitotic entry	[64]