Table 2.
PTMs modulating the activities of the GSDM family
| PTM | GSDM family | Modified residue | Effect | Ref. |
|---|---|---|---|---|
| Lys48-linked polyubiquitination (IpaH7.8) | GSDMB | At least Lys177, Lys190, Lys192 (human) | Promote degradation of GSDMB and directly inhibit pore formation | 38,160–163 |
|
Lys63-linked/ Lys48-linked polyubiquitination (IpaH7.8) |
GSDMD | LysK55, Lys62, Lys203 (human) | Promote degradation of GSDMD | 38,161–163 |
|
Lys27-linked Polyubiquitination (SYVN1) |
GSDMD | Lys203, Lys204/Lys204, Lys205 (human/mouse) | Promote pyroptosis | 303 |
|
Lys48-linked Polyubiquitination (CDC20) |
GSDME | Not mentioned | Promote degradation of GSMDE | 305 |
| Deubiquitination (USP24) | GSDMB | Not mentioned | Increase the stability of GSDMB | 304 |
| Deubiquitination (USP48 and OTUD4) | GSDME | Not mentioned | Increase the stability of GSDME | 306,307 |
| Phosphorylation (AMPK) | GSDME | Thr6 (human) | Prevent pore formation | 59,311 |
| Phosphorylation (PLK1) | GSDMA | Thr8 (human) | Prevent pore formation | 59,312 |
| Phosphorylation | GSDMD | Thr213 (human) | Prevent pore formation | 32 |
| Disulfiram | GSDMD | Cys191/Cys192 (human/mouse) | Prevent pore formation | 45 |
| Disulfiram | GSDME | Not mentioned | Prevent pore formation | 530 |
| Necrosulfamide | GSDMD | Cys191/Cys192 (human/mouse) | Prevent pore formation | 44 |
| Succination (fumarate) | GSDMD | Cys191/Cys192 (human/mouse) | Prevent cleavage and pore formation | 46 |
| Succination (fumarate) | GSDME | Cys45 (mouse) | Prevent pore formation | 46 |
| Itaconation | GSDMD | Cys77 (mouse) | Prevent caspase-1-dependent cleavage | 320 |
| Oxidation | GSDMD | Cys38, Cys56, Cys268, Cys467 (human) |
Promote cleavage by caspase-1 |
323 |
| Palmitoylation (ZDHHC5/9) | GSDMD | Cys191/Cys192 (human/mouse) | Promote pore formation and pyroptosis | 324,325 |
| Palmitoylation (ZDHHC-2/7/11/15) | GSDME | Cys407/Cys408 (human/mouse) | Promote pore formation and pyroptosis | 326 |
| Palmitoylation | bacterial and fungal GSDMs |
Cys3/Cys3/Cys4/Cys7 (Runella/ Bradyrhizobium/ Vitiosangium/Lysobacter) |
Promote structural stability and pore-forming activity | 228 |