Destabilization of EpCAM dimer is associated with increased susceptibility towards cleavage by TACE.
Dimerization
EpCAM
Proteolytic cleavage
TACE
Journal
PeerJ
ISSN: 2167-8359
Titre abrégé: PeerJ
Pays: United States
ID NLM: 101603425
Informations de publication
Date de publication:
2021
2021
Historique:
received:
11
03
2021
accepted:
27
04
2021
entrez:
31
5
2021
pubmed:
1
6
2021
medline:
1
6
2021
Statut:
epublish
Résumé
The cell-surface protein EpCAM is a carcinoma marker utilized in diagnostics and prognostics, and a promising therapeutic target. It is involved in nuclear signaling via regulated intramembrane proteolysis (RIP). Many aspects of this process are not fully understood, including the events at the molecular level leading to the exposure of cleavage sites, buried at the dimerization interface. To investigate the effect of dimer stability on cleavage susceptibility we prepared two mutants of human EpCAM ectodomain: a monomeric form, and a disulfide-stabilized dimeric form. We show that the disulfide-stabilized dimer is resistant to tumor necrosis factor-α-converting enzyme (TACE) cleavage, while the monomeric form is more susceptible than the predominantly dimeric wild type. This provides experimental evidence that the oligomeric state of EpCAM is a determinant in RIP and demonstrates the usefulness of the oligomeric state-specific mutants in investigations of EpCAM biological function.
Identifiants
pubmed: 34055495
doi: 10.7717/peerj.11484
pii: 11484
pmc: PMC8142927
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e11484Informations de copyright
© 2021 Žagar et al.
Déclaration de conflit d'intérêts
The authors declare that they have no competing interests.
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