Tumor progression and the different faces of the PERK kinase.

Abstract

The serine/threonine endoplasmic reticulum (ER) kinase, protein kinase R (PKR)-like ER kinase (PERK), is a pro-adaptive protein kinase whose activity is regulated indirectly by protein misfolding within the ER. As the oxidative folding environment in the ER is sensitive to a variety of cellular stresses, many of which occur during neoplastic transformation and in the tumor microenvironment, there has been considerable interest in defining whether PERK positively contributes to tumor progression and whether it represents a significant therapeutic target. Herein, we review the current knowledge of PERK-dependent signaling pathways, the contribution of downstream substrates including recently characterized new PERK substrates transcription factors Forkhead box O protein and diacyglycerol a lipid signaling second messenger, and efforts to develop small molecule PERK inhibitors.

• Authors: D Pytel, I Majsterek, J A Diehl
• Journal: Oncogene (Oncogene) Vol. 35 Issue 10 Pg. 1207-15 (Mar 10 2016) ISSN: 1476-5594 [Electronic] England
• PMID: 26028033 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• MicroRNAs
• PERK kinase
• eIF-2 Kinase

Topics

• Animals
• Disease Progression
• Humans
• MicroRNAs (genetics)
• Neoplasms (enzymology, genetics, pathology)
• Neurodegenerative Diseases (enzymology)
• Signal Transduction
• eIF-2 Kinase (antagonists & inhibitors, metabolism)