Table 2 PTMs modulating the activities of the GSDM family
From: The gasdermin family: emerging therapeutic targets in diseases
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 | |
Lys63-linked/ Lys48-linked polyubiquitination (IpaH7.8) | GSDMD | LysK55, Lys62, Lys203 (human) | Promote degradation of GSDMD | |
Lys27-linked Polyubiquitination (SYVN1) | GSDMD | Lys203, Lys204/Lys204, Lys205 (human/mouse) | Promote pyroptosis | |
Lys48-linked Polyubiquitination (CDC20) | GSDME | Not mentioned | Promote degradation of GSMDE | |
Deubiquitination (USP24) | GSDMB | Not mentioned | Increase the stability of GSDMB | |
Deubiquitination (USP48 and OTUD4) | GSDME | Not mentioned | Increase the stability of GSDME | |
Phosphorylation (AMPK) | GSDME | Thr6 (human) | Prevent pore formation | |
Phosphorylation (PLK1) | GSDMA | Thr8 (human) | Prevent pore formation | |
Phosphorylation | GSDMD | Thr213 (human) | Prevent pore formation | |
Disulfiram | GSDMD | Cys191/Cys192 (human/mouse) | Prevent pore formation | |
Disulfiram | GSDME | Not mentioned | Prevent pore formation | |
Necrosulfamide | GSDMD | Cys191/Cys192 (human/mouse) | Prevent pore formation | |
Succination (fumarate) | GSDMD | Cys191/Cys192 (human/mouse) | Prevent cleavage and pore formation | |
Succination (fumarate) | GSDME | Cys45 (mouse) | Prevent pore formation | |
Itaconation | GSDMD | Cys77 (mouse) | Prevent caspase-1-dependent cleavage | |
Oxidation | GSDMD | Cys38, Cys56, Cys268, Cys467 (human) | Promote cleavage by caspase-1 | |
Palmitoylation (ZDHHC5/9) | GSDMD | Cys191/Cys192 (human/mouse) | Promote pore formation and pyroptosis | |
Palmitoylation (ZDHHC-2/7/11/15) | GSDME | Cys407/Cys408 (human/mouse) | Promote pore formation and pyroptosis | |
Palmitoylation | bacterial and fungal GSDMs | Cys3/Cys3/Cys4/Cys7 (Runella/ Bradyrhizobium/ Vitiosangium/Lysobacter) | Promote structural stability and pore-forming activity |