Research Progress of Endoplasmic Reticulum Stress PERK-eIF2α-AFT4-CHOP Signaling Pathway in Hematological Malignancies
10.3971/j.issn.1000-8578.2024.23.0609
- VernacularTitle:内质网应激PERK-eIF2α-AFT4-CHOP信号通路在血液肿瘤中的研究进展
- Author:
Mengke HE
1
;
Zizhen XU
;
Junmin LI
Author Information
1. Department of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Publication Type:Research Article
- Keywords:
Endoplasmic reticulum stress;
Unfolded protein response;
PERK;
eIF2α;
ATF4;
CHOP;
Hematological malignancies
- From:
Cancer Research on Prevention and Treatment
2024;51(2):140-146
- CountryChina
- Language:Chinese
-
Abstract:
The biosynthesis and maturation of proteins are primarily regulated by the endoplasmic reticulum in its physiological state. Thus, the disruption of physiological homeostasis initiates the buildup of unfolded and misfolded proteins in the endoplasmic reticulum, resulting in endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). One of the important pathways by which UPR maintains intracellular homeostasis under ERS is activating protein kinase R-like endoplasmic reticulum kinase (PERK). The activation of the PERK pathway stimulates eukaryotic translation initiation factor 2 subunit-α (eIF2α) phosphorylation and the selective translation of active transcription factor 4 (ATF4), and PERK induces cell apoptosis by directly binding to the promoter of pro-apoptotic transcription factor C/EBP homologous protein (CHOP). This signaling pathway is also one of the important mechanisms by which UPR participates in the regulation of hematological malignancies and immune cells in a tumor microenvironment. This article provides an overview of advancements in research into the PERK-eIF2α-ATF4-CHOP signaling pathway in hematological malignancies and the potential therapeutic benefits of targeting this signaling pathway.
