TABLE 1.
Ferroptosis regulation by E3s and deubiquitylating enzymes (DUBs).
| Targets | Levels | E3s | DUBs | Biological functions | References |
| SLC7A11 | Post-translation | TRIM26 | Degrading SLC7A11; promoting ferroptosis | Zhu et al., 2021 | |
| OTUB1 | Stabilizing SLC7A11; suppressing ferroptosis | Liu T. et al., 2019; Chen S. et al., 2021 | |||
| Transcription | USP22 | Increasing SLC7A11 expression; suppressing ferroptosis | Ma et al., 2020 | ||
| Epigenetic | BAP1 | Suppressing SLC7A11 expression; promoting ferroptosis | Zhang et al., 2018 | ||
| PRC1 | Suppressing SLC7A11 expression; promoting ferroptosis | Zhang et al., 2019a | |||
| USP7 | Suppressing SLC7A11 expression; promoting ferroptosis | Wang Y. et al., 2019 | |||
| GPX4 | Post-translation | Unknown | Degrading GPX4; promoting ferroptosis | Yang L. et al., 2020; Ding et al., 2021 | |
| Transcription | FBXL2 | Suppressing GPX4 expression; promoting ferroptosis | Chen et al., 2020 | ||
| VDAC2/3 | Post-translation | NEDD4 | Degrading VDAC2/3; suppressing ferroptosis | Yang Y. et al., 2020 | |
| NRF2 | Post-translation | USP11 | Stabilizing NRF2; suppressing ferroptosis | Meng et al., 2021 | |
| KEAP1 | Degrading NRF2; promoting ferroptosis | Kansanen et al., 2013 | |||
| NCOA4 | Post-translation | HERC2 | Degrading NCOA4; suppressing ferroptosis | Mancias et al., 2015 | |
| Beclin1 | Post-translation | USP14 | Deubiquitylating Beclin1; suppressing ferroptosis | Tsai et al., 2020 | |
| ATG16L1 | Transcription | FBXW7 | Promoting ATG16L1 expression; promoting ferroptosis | Zhang et al., 2020 | |
| TFRC | Transcription | USP7 | Promoting TFRC expression; Promoting ferroptosis | Tang L.J. et al., 2021 | |
| FPN1 | Post-translation | RNF217 | Degrading FPN1;promoting ferroptosis | De Domenico et al., 2007; Jiang et al., 2021 | |
| IRP2 | Post-translation | FBXL5 | Degrading IRP2; suppressing ferroptosis | Dixon et al., 2012 | |
| OTUD1 | Stabilizing IRP2; promoting ferroptosis | Song et al., 2021b | |||
| LTF | Post-translation | NEDD4L | Degrading LTF; suppressing ferroptosis | Wang et al., 2020b | |
| LSH | Post-translation | CRL4- DCAF8 | Degrading LSH; promoting ferroptosis | Huang et al., 2020 | |
| HO-1 | Post-translation | SIAH2 | Degrading HO-1; suppressing ferroptosis | Chillappagari et al., 2020 | |
| Transcription | SIAH2 | Suppressing HO-1 expression; suppressing ferroptosis | Chillappagari et al., 2020 |
E3 ubiquitin ligases and DUBs are pivotally involved in ferroptosis through targeting multiple substrates, including solute carrier family 7 member 11 (SLC7A11), voltage-dependent anion channels (VDAC2/3), nuclear factor, erythroid 2-like 2 (NRF2), and iron regulatory protein 2 (IRP2).