Roles of CHOP/GADD153 in endoplasmic reticulum stress

Abstract

Endoplasmic reticulum (ER) is the site of synthesis and folding of secretory proteins. Perturbations of ER homeostasis affect protein folding and cause ER stress. ER can sense the stress and respond to it through translational attenuation, upregulation of the genes for ER chaperones and related proteins, and degradation of unfolded proteins by a quality-control system. However, when the ER function is severely impaired, the organelle elicits apoptotic signals. ER stress has been implicated in a variety of common diseases such as diabetes, ischemia and neurodegenerative disorders. One of the components of the ER stress-mediated apoptosis pathway is C/EBP homologous protein (CHOP), also known as growth arrestand DNA damage-inducible gene 153 (GADD153). Here, we summarize the current understanding of the roles of CHOP/ GADD153 in ER stress-mediated apoptosis and in diseases including diabetes, brain ischemia and neurodegenerative disease.

Rottlerin induces pro-apoptotic endoplasmic reticulum stress through the protein kinase C-δ-independent pathway in human colon cancer cells

“…3b). Other hallmarks of the ER stress responses include the activation of ATF6 and the subsequent induction of GRP78 and CHOP [2,10,23]. To analyze whether rottlerin induces ER stress in HT29 cells, we first examined the effect of rottlerin on the expression of CHOP and GRP78 by Western blotting.…”

“…The endoplasmic reticulum (ER) is the first organelle in the secretory pathway, and serves as a site of secretory protein synthesis and modification prior to transportation to Golgi bodies for export [1,2]. Proteins are correctly folded in the ER under normal conditions, but protein folding in the ER is impaired under various physiological and pathological conditions.…”

“…Proteins are correctly folded in the ER under normal conditions, but protein folding in the ER is impaired under various physiological and pathological conditions. These abnormalities in the ER are collectively called ER stress [1,2]. Cells display various adaptive responses to relieve ER stress.…”

A highly conserved proapoptotic gene, IKIP, located next to the APAF1 gene locus, is regulated by p53

“…5,6 Besides mitochondria, the endoplasmic reticulum (ER) has recently gained much attention for its role in apoptosis. 7,8 First, the ER can generate death signals of its own as the last consequence of the unfolded protein response. This can occur through activation of caspase-12, a caspase that is remarkably specific for ER stress-mediated apoptosis; 9 however, a caspase-12 independent pathway is also activated.…”

Disease-associated polymorphisms in ERAP1 do not alter endoplasmic reticulum stress in patients with ankylosing spondylitis

“…The ER-resident chaperone GRP78 (GRP78/BiP) is sequestered which then allows the activation of three main effector molecules: activating transcription factor 6, serine/ threonine-protein kinase/endoribonuclease IRE1 and PRKR-like ER kinase (PERK). 19 One arm of this pathway involves the activation of CHOP by PRKR-like ER kinase, ultimately resulting in the upregulation of pro-inflammatory cytokines such as IL23. 9 To assess whether AS-associated ERAP1 variants alter levels of ER stress, we compared the relative expression of ER-stress genes GRP78 and CHOP in peripheral blood mononuclear cells (PBMCs) from patients carrying either the risk or protective allele of rs30187.…”