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GSDME (1-270) binds PIPs
Stable Identifier
R-HSA-9647660
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol
,
plasma membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
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Programmed Cell Death (Homo sapiens)
Regulated Necrosis (Homo sapiens)
Pyroptosis (Homo sapiens)
GSDME (1-270) binds PIPs (Homo sapiens)
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Gasdermin E (GSDME/DFNA5) cleavage at D270 by caspase‑3 (CASP3) or by granzyme B (GZMB ) liberates the N‑terminal fragment of GSDME (GSDME(1-270)), which moves to the plasma membrane where it strongly binds to inner leaflet lipids such as phosphatidylinositol (4,5)‑bisphosphate (Rogers C et al. 2017; Wang Y et al. 2017). Residues 1–56 of GSDME include 19 hydrophobic ones thought to be involved in membrane targeting and penetration (Rogers C et al. 2017). Upon cleavage by CASP3, the liberated N‑terminal fragment of GSDME forms pores in the plasma membrane to either drive cells directly into pyroptosis or induce secondary necrosis after apoptosis in cells with low expression level of GSDME (that is insufficient to override the CASP3-mediated apoptotic program) (Rogers C et al. 2017; Wang Y et al. 2017).
Literature References
PubMed ID
Title
Journal
Year
28045099
Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic/pyroptotic cell death
Cingolani, G
,
Rogers, C
,
Mayes, L
,
Alnemri, D
,
Alnemri, ES
,
Fernandes-Alnemri, T
Nat Commun
2017
Participants
Input
GSDME(1-270) [cytosol]
(Homo sapiens)
PI4P,PI(4,5)P2,PIP3 [plasma membrane]
Output
GSDME (1-270):PIPs [plasma membrane]
(Homo sapiens)
Participates
as an event of
Pyroptosis (Homo sapiens)
Orthologous Events
GSDME (1-270) binds PIPs (Bos taurus)
GSDME (1-270) binds PIPs (Canis familiaris)
GSDME (1-270) binds PIPs (Danio rerio)
GSDME (1-270) binds PIPs (Gallus gallus)
GSDME (1-270) binds PIPs (Mus musculus)
GSDME (1-270) binds PIPs (Rattus norvegicus)
GSDME (1-270) binds PIPs (Sus scrofa)
GSDME (1-270) binds PIPs (Xenopus tropicalis)
Authored
Shamovsky, V (2020-11-09)
Reviewed
D'Eustachio, P (2021-02-17)
Kanneganti, TD (2021-02-17)
Shao, F (2021-04-22)
Created
Shamovsky, V (2019-06-03)
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