Table 2.
List of non-proteolytic ubiquitylation events described in different disease-mediating processes.
| E2/E3/DUB | Substrate | Ub Linkage | Phenotype | Reference |
|---|---|---|---|---|
| Cancer | ||||
|
SMURF1 (E3) ZRANB1 (DUB) |
UVRAG | K29, K33 | Promotes autophagosome maturation and inhibits HCC tumor growth | 115 |
| ITCHβ-Arrestin2 (E3) | SuFu | K63 | Increases SuFu binding to Gli transcription factors and controls medulloblastoma tumorigenesis downstream of Hedgehog signaling | 116 |
| ITCH (E3) | BRAF | K27 | Promotes melanoma proliferation and invasion downstream of ERK signaling | 117 |
| CUL4AMBRA1 | SMAD4 | K63 | Promotes EMT, migration, invasion and metastasis of breast cancer cells downstream of TGF-β signaling | 119 |
| RNF181 (E3) | YAP | K48 | Promotes Triple Negative Breast Cancer cell proliferation, migration and invasion downstream of Hippo signaling | 120 |
| UBE2S (E2) | β-Catenin | K11 |
a) Promotes differentiation of embryonic stem cells into mesoendoderm lineages b) Promotes colorectal cancer cell proliferation and metastasis |
121 |
| TRAF4 (E3) | TRKA | K27, K29 | Promotes prostate cancer cell migration, invasion and metastasis | 122 |
| CBLC (E3) | EGFR | K6, K11 | Inhibits EGFR lysosomal degradation and promotes lung cancer cell viability | 39, 123 |
| Metabolism-related diseases | ||||
| SMURF1 (E3) | PPARγ | K63 | Suppresses PPARγ transcriptional activity and inhibits lipid accumulation in the liver, protecting from NAFLD | 125 |
| UBE2N/UBC13 (E2) | Akt | K63 | Regulates insulin sensitivity in a GPS2-dependent manner to control lipid accumulation and obesity | 133 |
| HECTH9/HUWE1 (E3) | HK2 | K63 | Promotes glucose metabolism, cancer stem cell (CSC) expansion and CSC-associated chemoresistance | 138 |
| Parkin (E3) OTUB2 (DUB) | PKM2 | ? | Regulates PKM2 enzymatic activity and glycolysis | 139, 140 |
| Innate Immunity-related diseases | ||||
| OTUD1 (DUB) | IRF3 | K6, K63 | Attenuates inflammatory response after HSV-1 and VSV infection | 142, 143 |
| HECTD3 (E3) | MALT1, STAT3 | K27, K29 | Promotes differentiation of Th17 cells downstream of NF-kB activation | 147 |
| SCFSkp1-Cullin1-Fbxo21 (E3) | ASK1 | K29 | Promotes type I interferon production upon VSV and HSV-1infection | 149 |
| CUL4DCAF12L1/ DCAF11 (E3) | PB2 | K29 | Promotes Influenza A Virus (IAV) infection | 150 |
| TRIM21 (E3) | MAVS | K27 | Activates innate immune response and inhibits RNA viral infection | 151 |