Table 1 Summary of E3 ligases and deubiquitinases involved in the tumor microenvironment

E3 ligases

 NEDD4

Neuronal precursor cell expressed developmentally downregulated 4

PD-L1

[92]

 SPOP

Speckle-type BTB/POZ protein

PD-L1

[30]

 β-TrCP

β-transducin repeat-containing protein

PD-L1, VEGFR2

[94, 135]

 HRD1

HMG-coA reductase degradation protein 1

PD-L1

[95]

 Cbl-b

Casitas B lymphoma-b

[96]

 c-Cbl

c-Caritas B cell lymphoma

PD-1, PLC-γ1, MMP2

[96, 103, 139, 203]

 TRAF6

Tumor necrosis factor receptor-associated factor 6

PD-L1, HIF-1α, STAT6, Foxp3, STAT3

[97, 118, 149, 160, 188]

 FBXO38

F-box protein 38

PD-1

[104, 105]

 KLHL22

Kelch-like family member 22

PD-1

[106]

 VHL

Von Hippel-Lindau

HIF-1α

[110]

 Siah1/2

Seven in absentia homologue 1/2

PHDs

[111]

 FBW7

F-box and WD repeat domain-containing 7

HIF-1α, c-Myc

[112, 145]

 Mdm2

Mouse double minute 2

HIF-1α

[114, 115]

 HAF

Hypoxia-associated factor

HIF-1α

[116]

 Nrdp1

Neuregulin receptor degradation protein-1

USP8

[123]

 HectH9

USP7

[125]

 β-TrCP1

β-transducin repeat-containing protein 1

VEGFR2

[134]

 SIAH2

Seven in absentia homolog 2

NRF1

[146]

 Praja2

MFHAS1

[147]

 Trim24

Tripartite motif containing protein 24

CBP

[148]

 Stub1

STIP1 homology and U-box-containing protein 1

Foxp3

[157]

 RNF31

Ring finger protein 31

Foxp3

[158]

 Rnf20

Ring finger protein 20

Foxp3

[161]

 Hakai

E-cadherin

[177]

 RNF43

RING finger protein 43

E-cadherin

[179]

 NRBE3

Novel RB E3 ubiquitin ligase

RB

[180]

 UBR5

ubiquitin protein ligase E3 component n-recognin 5

Snail1, Twist, FBP1

[182, 204]

 TRIM21

Tripartite motif containing protein 21

FASN

[206]

Deubiquitinases

 USP8

Ubiquitin-specific protease 8

PD-L1, HIF-1α, VEGFR2

[97, 121, 136]

 USP9X

Ubiquitin-specific peptidase 9, X-linked

PD-L1

[98]

 CSN5

COP9 signalosome 5

PD-L1

[99]

 USP22

Ubiquitin-specific protease 22

PD-L1, Foxp3

[100, 161]

 USP7

Ubiquitin-specific protease 7

PD-L1, HIF-1α, Foxp3, Tip60

[101, 125, 162, 163]

 USP28

Ubiquitin-specific protease 28

HIF-1α

[113]

 USP25

Ubiquitin-specific protease 25

HIF-1α

[119]

 UCHL1

Ubiquitin C-terminal hydrolase L1

HIF-1α

[120]

 USP20

Ubiquitin-specific protease 20

HIF-1α

[122]

 MCPIP1

Monocyte chemoattractant protein-induced protein 1

HIF-1α

[126]

 USP19

Ubiquitin-specific protease 19

NLRP3

[127, 152]

 OTUD5

ovarian tumor deubiquitinase 5

YAP

[151]

 USP10

Ubiquitin-specific protease 10

NLRP7

[153]

 USP44

Ubiquitin-specific protease 44

Foxp3

[164]

 USP21

Ubiquitin-specific protease 21

Foxp3

[165]

 USP48

Ubiquitin-specific protease 48

TRAF2

[181]

 USP17

Ubiquitin-specific protease 17

HAS2

[199]

 USP4

Ubiquitin-specific protease 4

HAS2

[199]