Table 1.

E3 ubiquitin ligases in Glioblastoma (GBM).

Name	Function	Target/Substrate	Reference
RING E3 Ligases
A20	Inhibition of TRAIL-induced apoptosis via RIP1 K63-polyubiquitination	RIP1	(168)
APC/C	Cell cycle regulation Regulation of GSCs via CDC20-APC/SOX2 signaling axis	CDC20, KIF11, SOX2	(169–171)
BIRC3	Hypoxic adaptation in mesenchymal GBM	?	(172)
BRE1	Polyubiquitination of tumor suppressor p42 Ebp1	Ebp1	(173)
c-Cbl	Regulation of αPix-mediated cell migration and invasion Negative regulation of PI3K-AKT pathway via neddylation of c-Src	αPix, c-Src	(174, 175)
CHIP	Regulation of PI3K/AKT signaling via the CHIP/miR-92b/PTEN regulatory network CSN6-CHIP-EGFR signaling axis	EGFR, PTEN	(176, 177)
CUL4B	Knockdown induced G1 arrest and decreased expression of cyclin D1	?	(178)
HOIL-1L	Hypoxic adaptation via HIF1-dependent PKCζ degradation	PKCζ	(179)
IAP1	Regulation of c-Myc and NFκB signaling	ASK1, IAP2, MAD1/4, TRAF2	(180)
IAP2	Negatively regulates XIAP stabilization of mature Smac and Bcl10 Regulation of NFκB signaling	XIAP	(181)
LZTR1/CUL3	Regulation of the RAS/MAPK signaling cascade	RAS	(182)
MDM2/HDM2	Overexpression provides escape from p53-regulated growth control Associated with multi-drug resistant phenotype Regulation of HIF1α in a PTEN-PI3K-AKT-dependent manner	HIF1α, p53	(183–185)
MEX3A	Regulates tumor suppressor RIG-I	RIG-I	(186)
NRDP1	Negative regulator of non-canonical Wnt signaling	Disheveled, Vangl1/2	(187)
nXIAP	Regulation of NFκB activation and apoptosis Inhibits IAP2 autoubiquitination	Caspase 3/7/9, IAP2, TAK1/TAB1	(181, 188)
PRAJA1	Overexpressed in gliomas with inverse relationship to cell cycle regulator and apoptotic genes Mediates degradation of CIC, possibly contributing to hyperactive RTK/Ras/ERK signaling	Capicua (CIC)	(189, 190)
PRAJA2	Degradation of NDR/LATS kinase component Mob, attenuating the Hippo cascade and sustaining tumor growth	Mob	(191)
RAD18	Knockdown reduced cell viability and invasive capacity	?	(192)
RBX1/ROC1 (SCF)	Silencing induces G2-M arrest, apoptosis and senescence	?	(193)
RNF123	miR-155-5p-RNF123-NF-κB1-p50-SerpinE1 signaling axis	NFκB?	(194)
RNF135	Knockdown induced G0/G1 arrest and attenuation of p-ERK activation	RIG1	(195)
RNF138	Downregulation attenuated tumour growth and reversed EMT, possibly via Erk signaling pathway Degradation of rpS3 provides mechanism for radioresistance	rpS3	(196, 197)
RNF144	Epigenetic regulation Downregulation under hypoxic stress in mesenchymal GSCs increases cell survival	BMI1	(198)
RNF168	Reduced expression of RNF168 in MTAB-deficient GBM cells leads to H2AX destabilisation	H2AX	(199)
SCFβ-TrCP	Regulation of GBM stem cell maintenance/differentiation Nuclear mislocalization induces PI3K/Akt and Wnt/β-catenin pathway dysregulation	β-catenin, PHLPP1, REST	(200–202)
SCFFbw7	Tumor suppressor commonly mutated in GBM Enhances BNIP3-mediated hypoxic cell death via Mcl-1 degradation Silencing reduced G2/M arrest and apoptosis	Aurora-A/B, c-Jun, c-Myc, Cyclin E, Mcl-1, Notch1/4, SOX9	(203–206)
SCFFBXL14	Antagonizes USP13-mediated c-Myc stabilization, negatively regulating GSC self-renewal	c-Myc	(207)
SCFFBXO16	Low expression in GBM results in active Wnt signalling	β-catenin	(208)
SCFSKP2	Regulation of p27 stability via PTEN/PI3-kinase pathway Senescence and cell cycle regulation Knockdown resulted in chemosensitization and reduced sphere formation ability	p21Cip1/Waf1/Sdi1, p27KIP1	(209–212)
SHPRH	Tumor suppressive phenotype	PCNA	(213)
SIAH1	Proapoptotic role in GBM p53WT cells	HIPK2, p27	(214, 215)
TRAF2	Silencing induces G2-M arrest and radiosensitization NO induced CREB phosphorylation via IRE1-α/TRAF2/JNK axis Regulation of NFκB signaling	IRE1-α, SGEF/Rac1	(216–218)
TRIM3	Regulation of stem cell dynamics and asymmetric cell division Regulation of c-Myc and Musashi–Notch signaling	?	(219)
TRIM8	Regulation of stemness via STAT3 signaling	PIAS3	(220, 221)
TRIM9s	Enhances p38 signaling via K63-uniquitination of MKK6	MKK6	(222)
TRIM11	Overexpression promoted a stem-like phenotype Exerts oncogenic effect through EGFR pathway	?	(223)
TRIM14	Promotes EMT by regulating ZEB2 stability	ZEB2	(224)
TRIM33	Degradation of nuclear β-catenin	β-catenin	(225)
TRIM45	Stabilizes p53 via K63-polyubiquitination	p53	(226)
VHL	Regulation of JAK/STAT and hypoxic signaling and Wnt/β-catenin pathway Regulation of angiogenesis via VEGF	β-catenin, HIF-1α	(227–229)
RING-Between-RING E3 Ligases
PARKIN	PARK2 mutations lead to cyclin E dysregulation and mitotic instability Degradation of APE1 under cellular stress Negative regulation of EMT via ZEB1	APE1, Cyclin E	(85, 230, 231)
HECT E3 Ligases
HECTD1	Negative regulation of Wnt pathway	Adenomatous polyposis coli?	(232)
HERC3	Promotes autophagy-induced EMT via SMAD7/TGF-β signaling	SMAD7	(233)
HUWE1 (Mule)	Regulation of N-Myc transcriptional activity	N-Myc	(234, 235)
ITCH/AIP4	Regulation of FLIPs stability via PTEN-Akt-AIP4 pathway	FLIPs	(236)
NEDD4	FoxM1B-induced degradation/downregulation of PTEN	PTEN	(237)
SMURF1	Knockdown reduced cell invasion Correlates with poor prognosis	?	(238)
SMURF2	Dysregulation of TGF-β signaling	TβR-I	(239)
UBE3B	Knockdown sensitized cells to chemotherapeutic and resulted in mitochondrial fragmentation Regulation of mitochondrial oxidative stress response	Calmodulin	(240, 241)
UBE3C	Knockdown decreased cell migration and invasion Ubiquitination of tumor suppressor ANXA7	Annexin A7	(242)
SUMOylase
NUSAP1	Stabilizes DNA damage sensor ATR Increased chemotherapeutic resistance	ATR	(243)
PIAS1	Mediates STI1 nuclear retention during DNA-damage response Regulates stability of RNA helicase, DDX39B	DDX39B, STI1	(244, 245)

Name function, target/substrates and references are depicted for E3 ubiquitin ligases implicated by the literature to play a role in GBM.