Table 1.
Neddylation targets
| Neddylated protein | E1/E2/E3 | NEDD8 Protease | Modified Sites | Consequence of Neddylation | Ref |
|---|---|---|---|---|---|
| Regulation of UPS | |||||
| Cullins | NAE/Ubc12/DCN1 | CSN | C-terminal lysine | Induces the assembly of CRLs | [65,74] |
| Parkin | NAE/-/- | - | K76 | Increases ubiquitin ligase activity | [33,34] |
| Mdm2 | -/Ubc12/Mdm2 | NEDP1 | - | Increases the stability | [27,50] |
| Smurf1 | -/Ubc12/Smurf1 | - | Multiple lysines | Increases ubiquitin ligase activity | [76] |
| XIAP | -/Ubc12/IAP | NEDP1 | - | ? | [30,126] |
| Ubiquitin | UBE1/-/- | CSN? | K29 | Terminate ubiquitin chain extension? | [20,79] |
| Regulation of transcription factors | |||||
| E2F1 | NAE/-/- | NEDP1 | Multiple lysines | Decreases the stability and transcriptional activity | [83,84] |
| HuR | -/-/Mdm2 | NEDP1 | K283, 313, 326 | Enables nuclear localization and stabilization, increases transcriptional activity | [26] |
| HIF1α | NAE/-/- | - | - | Increases protein stability and activity | [69] |
| AICD/APP | - | - | Multiple lysines | Inhibits the transcriptional activity | [127] |
| RCAN1 | - | - | K96, 104, 107 | Increases protein stability | [78] |
| BCA3 | - | NEDP1 | Multiple lysines | Increases its binding to p65; recruits SIRT1 | [49] |
| BRAP2 | - | - | K432 | Promotes NF-κB nuclear translocation and transcription activity | [128] |
| P73 | SMC/-/Mdm2 | NEDP1 | K321,327, 331 | Promotes cytoplasmic localization; inhibits transcription activity | [28] |
| Regulation of p53 signaling | |||||
| P53 | NAE/-/Mdm2 (FBOX11) | NEDP1 | K370, 372, 373 | Inhibit the transcriptional activity | [27,50,90] |
| L11 | - | NEDP1 | - | Increases stability; enhances P53 activity | [67] |
| S14 | -/-/HDM2 | NEDP1 | - | Increases stability; enhances P53 activity | [92] |
| Regulation of receptor-mediated signaling | |||||
| EGFR | NAE/Ubc12/c-Cbl | - | Multiple lysines | Reduces its stability | [72] |
| TGFβRII | NAE/Ubc12/c-Cbl | - | K556, 567 | Stabilizes TGFβRII, promotes TGFβ signaling | [66] |
| Regulation of cell death effectors | |||||
| Caspase7? | NAE/Ubc12/IAP1 | NEDP1 | K142 and others | Inhibits caspase activity | [30,126] |
| RIPK1 | -/-/cIAP1 | - | - | - | [30] |
| Caspase1? | NAE/-/- | - | - | Activates catalytic activity | [129] |
| Others | |||||
| pVHL | - | - | K159 | Inhibits its binding to cul2; Promotes fibronectin matrix assembly | [70,71] |
| PINK1 | NAE/-/- | - | - | Stabilizes its 55kD cleaved form | [33] |
| SHC | NAE/Ubc12/- | - | K3 | Forms ZAP70-SHC-Grb2 complex; activates Erk | [11] |
| Histone H4 | -/Ubc12/RNF111 | - | N-terminal lysines | Alters the chromatin orientation for DNA repair | [130] |