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

38,160,161,162,163

Lys63-linked/ Lys48-linked

polyubiquitination (IpaH7.8)

GSDMD

LysK55, Lys62, Lys203 (human)

Promote degradation of GSDMD

38,161,162,163

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