Abstract
C/EBP homologous protein (CHOP), known also as DNA damage-inducible transcript 3 and as growth arrest and DNA damage-inducible protein 153 (GADD153), is induced in response to certain stressors. CHOP is universally acknowledged as a main conduit to endoplasmic reticulum stress-induced apoptosis. Ongoing research established the existence of CHOP-mediated apoptosis signaling networks, for which novel downstream targets are still being determined. However, there are studies that contradict this notion and assert that apoptosis is not the only mechanism by which CHOP plays in the development of pathologies. In this review, insights into the roles of CHOP in pathophysiology are summarized at the molecular and cellular levels. We further focus on the newest advances that implicate CHOP in human diseases including cancer, diabetes, neurodegenerative disorders, and notably, fibrosis.
Highlights
C/EBP homologous protein (CHOP), known as growth arrest and DNA damage-inducible protein 153 (GADD153), belongs to the CCAAT/enhancer-binding protein (C/EBP) family
In light of the data, a distinct model of apoptosis proposed with an unfolded protein response (UPR) cycle places CHOP in an obligatory step upstream of Growth Arrest and DNA-Damage-Inducible Protein 34 (GADD34) that dephosphorylates p-eukaryotic translation initiator factor 2α (eIF2α) and resumes global protein synthesis, which is the decisive matter of cell fate [89]
Induction of CHOP is converged from the regulation of UPR, integrated stress response (ISR), and mitogen-activated protein kinases (MAPKs) signaling in response to various cellular stress conditions, including endoplasmic reticulum (ER) stress and Reactive Oxygen Species (ROS)
Summary
C/EBP homologous protein (CHOP), known as growth arrest and DNA damage-inducible protein 153 (GADD153), belongs to the CCAAT/enhancer-binding protein (C/EBP) family. Much of our understanding of CHOP originates from the roles it plays during endoplasmic reticulum (ER) stress [1] and amino acid limitation [2]. It was gradually discovered as a stress-responsive transcription factor during growth arrest, DNA damage, nutrient deprivation, hypoxia, genotoxic agents, etc. Cells activate a series of adaptive pathways, namely the UPR, to restore homeostasis. Another innate protective pathway to proteostatic regulation is the ISR [5]
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