Table 3.
The roles of E3 ubiquitin ligases and deubiquitinases in ciliogenesis, ciliopathy, and cancer.
| E3 Ligase or DUB | The Role in Ciliogenesis (Substrate) | The Role in Ciliopathy and/or Cancer | References |
|---|---|---|---|
| CRL3-KCTD17 | inhibited by KD of KCTD17 (TCHP) | KO of KCTD17 causes situs inversus in zebrafish | [33], this paper (Figure 1) |
| USP8 | stimulated by KD of USP8 (TCHP) | KO of USP8 causes cystic kidney in zebrafish | [34] |
| USP8 is highly expressed and oncogenic in melanoma | [124] | ||
| Inhibition of USP8 suppresses the proliferation of glioblastoma stem cells | [125] | ||
| MARCHF7 | inhibited by OE of MARCHF7 (IQCB1) | MARCHF7 promotes proliferation and invasion of cervical cancer cells | [126,127] |
| TRIM32 | inhibited by OE of TRIM32 (IQCB1) | TRIM32 is a causative gene of BBS (BBS11) | [126,127] |
| TRIM32 is oncogenic in head and neck squamous cell carcinoma and skin cancer | [128,129] | ||
| USP9X | inhibited by KD of USP9X (IQCB1) | LOF mutations in USP9X cause phenotypes related to ciliopathy | [126,130] |
| USP9X is a major tumor suppressor gene in pancreatic ductal adenocarcinoma | [131] | ||
| CYLD | inhibited by KD/KO of CYLD (CEP70, MIB1) | KO/KD of CYLD causes ciliopathy-related phenotype in mouse and zebrafish | [132,133,134] |
| LOF mutation in CYLD cause skin cancer (familial cylindromatosis) | [135] | ||
| MIB1 | inhibited by OE of MIB1 (PCM1, KIAA0586) | MIB1 is oncogenic in upper urinary-tract urothelial carcinomas | [133,136,137] |
| CRL2-VHL | stimulated by OE of VHL (HIF1A) | KO of VHL causes cystic kidney | [138,139] |
| VHL is tumor-suppressive in renal cancers | [140] |
DUBs—deubiquitinases; KD—knockdown; KO—knockout; OE—overexpression; LOF—loss-of-function.