Keratin 8 is a scaffolding and regulatory protein of ERAD complexes.
Cytoskeleton
Epithelium
Intermediary filaments
Protein complexes fractionation
Protein–protein interaction
Synthetic lethality
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
received:
07
02
2022
accepted:
12
08
2022
revised:
08
08
2022
entrez:
31
8
2022
pubmed:
1
9
2022
medline:
9
9
2022
Statut:
ppublish
Résumé
Early recognition and enhanced degradation of misfolded proteins by the endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD) cause defective protein secretion and membrane targeting, as exemplified for Z-alpha-1-antitrypsin (Z-A1AT), responsible for alpha-1-antitrypsin deficiency (A1ATD) and F508del-CFTR (cystic fibrosis transmembrane conductance regulator) responsible for cystic fibrosis (CF). Prompted by our previous observation that decreasing Keratin 8 (K8) expression increased trafficking of F508del-CFTR to the plasma membrane, we investigated whether K8 impacts trafficking of soluble misfolded Z-A1AT protein. The subsequent goal of this study was to elucidate the mechanism underlying the K8-dependent regulation of protein trafficking, focusing on the ERAD pathway. The results show that diminishing K8 concentration in HeLa cells enhances secretion of both Z-A1AT and wild-type (WT) A1AT with a 13-fold and fourfold increase, respectively. K8 down-regulation triggers ER failure and cellular apoptosis when ER stress is jointly elicited by conditional expression of the µ
Identifiants
pubmed: 36045259
doi: 10.1007/s00018-022-04528-3
pii: 10.1007/s00018-022-04528-3
doi:
Substances chimiques
Keratin-8
0
Transcription Factors
0
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
503Subventions
Organisme : Agence Nationale de la Recherche
ID : ANR-13-BSV1-0019-01
Organisme : Agence Nationale de la Recherche
ID : ANR-18-CE14-0004
Organisme : Chancellerie des Universités de Paris
ID : 15LEG005_9UMS1151
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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