Table 1.
NEDD8 Pathway Substrates
| Substrates | E3 ligase | Function of neddylation | References |
|---|---|---|---|
| Cullins | RBX1/2 and/or DCN1 | Increases CRL activity | 43, 57, 66, 67, 90, 109 |
| p53 | MDM2 and SCFFBXO11 | Inhibits p53 transcriptional activity | 3, 150 |
| p73 | MDM2 | Inhibits p73 transcriptional activity | 142 |
| MDM2 | MDM2 | Increases Mdm2 stability | 150 |
| Ribosomal proteins (L11, S14) | MDM2 | Increases ribosomal protein stability | 133, 151, 159 |
| HuR | MDM2 | Controls the nuclear localization of HuR and protects it from degradation | 30 |
| EGFR | c-CBL | Enhances the efficiency of EGFR ubiquitination and facilitates its degradation | 108 |
| TGF-βRII | c-CBL | Stabilizes TGF-βRII by antagonizing ubiquitination and degradation | 170 |
| HIF1α/HIF2α | Increases protein stability | 118 | |
| BCA3 | Recruits histone deacetylase SIRT1 that represses NFκB-dependent transcription | 35 | |
| AICD | Inhibits AICD-mediated transcriptional activation via the inhibition of its interaction with the transcription coactivators Fe65 and Tip60 | 72 | |
| E2F-1 | Reduces E2F-1 stability, transcriptional activity, and cell growth | 80 | |
| IKKγ | TRIM40 | Inhibits NF-κB activity | 100 |
| SHC | Facilitates the formation of a ZAP70-Shc-Grb2 signaling complex and affects downstream Erk activation | 51 | |
| Caspases/IAPs/RIP1 | IAPs | Suppresses caspase activity | 9, 97 |
| RCAN1 | Increases RCAN1 stability by inhibiting proteasomal degradation of RCAN1 and increases RCAN1 binding to calcineurin | 101 | |
| pVHL | Prevents pVHL interaction with Cul2-containing complexes, promotes pVHL association with fibronectin, and the assembly of extracellular matrix | 130 | |
| Parkin/PINK1 | Increases parkin E3 ligase activity and stabilizes PINK1 55 kDa fragment | 13, 140 | |
| Histone H4 | RNF111 | Activates DNA damage-induced ubiquitination | 84 |
AICD, APP intracellular domain; BCA3, breast cancer-associated protein 3; c-CBL, casitas B-lineage lymphoma; CRL, cullin-RING ligase; DCN1, defective in cullin neddylation 1; E2F-1, E2F transcription factor 1; EGFR, epidermal growth factor receptor; HIF1, hypoxia-inducible factor-1; HIF2, hypoxia-inducible factor-2; HuR, Hu antigen R; IAPs, inhibitors of apoptosis; MDM2, murine double minute-2; PINK1, PTEN induced putative kinase 1; pVHL, von Hippel-Lindau protein; RCAN1, regulator of calcineurin 1; RING, really interesting new gene; RNF111, ring finger protein 111; TGFβ-RII, transforming growth factor β type II receptor.