Abstract
The unfolded protein response (UPR) is an evolutionarily conserved stress response to intra- and extracellular conditions that disrupt endoplasmic reticulum (ER) protein-folding capacity. The UPR is engaged by a variety of disease conditions, including most cancers as well as both metabolic and neurodegenerative disorders. Three transmembrane transducers—PERK, IRE1, and ATF6—are responsible for activating downstream signaling pathways that mediate the UPR and subsequent stress response pathways. PERK, an ER resident transmembrane protein kinase, initiates both pro-apoptotic and pro-survival signaling pathways. In the context of neoplasia, PERK and its downstream targets alter gene expression that can be both pro- and anti-tumorigenic. In this review, we discuss recent advances in understanding how canonical and non-canonical PERK-mediated signaling pathways influence cell fate, tumor progression, and tumor suppression and avenues for therapeutic intervention.
Highlights
The endoplasmic reticulum (ER) is the site of post-translational modification, folding, maturation, and secretion for transmembrane and secreted proteins
As a result of the accumulation of misfolded proteins, an evolutionarily conserved stress response known as the unfolded protein response (UPR) is activated
C/EBP homologous protein (CHOP) induces expression of lnc-mGC, a long non-coding RNA (lncRNA) that binds a megacluster of 40 miRNAs and promotes cell death through changes in multiple miRNA-mediated translation regulation pathways[60]
Summary
F1000 Faculty Reviews are written by members of the prestigious F1000 Faculty. They are commissioned and are peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. The reviewers who approved the final version are listed with their names and affiliations. Any comments on the article can be found at the end of the article
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