Characterization of a PERK Kinase Inhibitor with Anti-Myeloma Activity.
PERK
UPR
apoptosis
bortezomib
cell survival
multiple myeloma
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
05 Oct 2020
05 Oct 2020
Historique:
received:
01
09
2020
revised:
21
09
2020
accepted:
01
10
2020
entrez:
8
10
2020
pubmed:
9
10
2020
medline:
9
10
2020
Statut:
epublish
Résumé
Due to increased immunoglobulin production and uncontrolled proliferation, multiple myeloma (MM) plasma cells develop a phenotype of deregulated unfolded protein response (UPR). The eIF2-alpha kinase 3 [EIF2αK3, protein kinase R (PKR)-like ER kinase (PERK)], the third known sensor of endoplasmic reticulum (ER) stress, is a serine-threonine kinase and, like the other two UPR-related proteins, i.e., IRE1 and ATF6, it is bound to the ER membrane. MM, like other tumors showing uncontrolled protein secretion, is highly dependent to UPR for survival; thus, inhibition of PERK can be an effective strategy to suppress growth of malignant plasma cells. Here, we have used GSK2606414, an ATP-competitive potent PERK inhibitor, and found significant anti-proliferative and apoptotic effects in a panel of MM cell lines. These effects were accompanied by the downregulation of key components of the PERK pathway as well as of other UPR elements. Consistently,
Identifiants
pubmed: 33028016
pii: cancers12102864
doi: 10.3390/cancers12102864
pmc: PMC7601861
pii:
doi:
Types de publication
Journal Article
Langues
eng
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