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Transcription Factor CHOP

About: Transcription Factor CHOP is a research topic. Over the lifetime, 443 publications have been published within this topic receiving 46408 citations.


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Proceedings ArticleDOI
Kan He1, Xingnan Zheng1, Mei Li1, Lin Zhang1, Jian Yu1 
TL;DR: Activation of ER stress and the death receptor pathway as a novel anticancer mechanism of mTOR inhibitors is established, and apoptosis plays a key role in their anti-tumor activities in colon cancer cells and xenografts through the DR5, FADD and caspase-8 axis.
Abstract: The mammalian target of rapamycin (mTOR) is commonly activated in colon cancer. mTOR complex 1 (mTORC1) is a major downstream target of the PI3K/ATK pathway and activates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. Rapamycin analogs Everolimus and Temsirolimus are non-ATP-competitive mTORC1 inhibitors, and suppress proliferation and tumor angiogenesis and invasion. We now show that apoptosis plays a key role in their anti-tumor activities in colon cancer cells and xenografts through the DR5, FADD and caspase-8 axis, and is strongly enhanced by TRAIL and 5-fluorouracil. The induction of DR5 by rapalogs is mediated by the ER stress regulator and transcription factor CHOP, but not the tumor suppressor p53, upon rapid and sustained inhibition of 4E-BP1 phosphorylation, and attenuated by eIF4E expression. ATP-competitive mTOR/PI3K inhibitors also promote DR5 induction and FADD-dependent apoptosis in colon cancer cells. These results establish activation of ER stress and the death receptor pathway as a novel anticancer mechanism of mTOR inhibitors. Citation Format: Kan He, Xingnan Zheng, Mei Li, Lin Zhang, Jian Yu. mTOR inhibitors induce apoptosis in colon cancer cells via CHOP-dependent DR5 induction upon 4E-BP1 dephosphorylation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-040. doi:10.1158/1538-7445.AM2015-LB-040

6 citations

Journal ArticleDOI
TL;DR: The role of CHOP/GADD153 in unstable atherosclerotic plaque formation isolated from confounding factors such as diabetes mellitus, primary hyperlipidemia, autoimmune deficiencies/abnormalities, essential hypertension, chronic heart failure, chronic kidney disease, and smoking is clarified.
Abstract: Background and aims: The signaling protein C/EBP homologous protein (CHOP) and corresponding growth-arrest-and-DNA-damage-inducible gene 153 (GADD153) is associated with endoplasmic reticulum stress (ERS), which can lead to apoptosis Our study aims to elucidate the role of CHOP/GADD153 in unstable atherosclerotic (AS) plaque formation isolated from confounding factors such as diabetes mellitus, primary hyperlipidemia, autoimmune deficiencies/abnormalities, essential hypertension, chronic heart failure, chronic kidney disease, and smokingMaterial and methods: We collected carotid artery tissue samples from patients aged 50–80 years-old who received carotid endarterectomies (CEA) at our institution We obtained fresh AS plaque samples during CEA and preserved the specimens immediately in the operating room with liquid nitrogen Samples were categorized as stable or unstable AS plaques according to a six-stage histologic classification CHOP/GADD153 expression was then examined with immunohistochem

5 citations

Journal ArticleDOI
TL;DR: This study concludes that CHOP 5'UTR-c.279T>C and +nt30C>T genotypes and haplotypes are not associated with tumors/cancer and pre-obesity and more studies are warranted to establish the role of CHOP variants in tumor/cancer predisposition and in overweight condition.
Abstract: Background Type 2 diabetes (T2D) is associated with obesity and has been shown recently to be associated with tumors/cancer. HNF1-beta and JAZF1 genes are associated with T2D and prostate cancer. We have previously shown that CHOP 5'UTR-c.279T>C and +nt30C>T haplotype variants contribute to T2D. CHOP deficiency causes obesity in mice, thus CHOP gene variants may contribute to human obesity. Furthermore, CHOP mediates apoptosis and is implicated in cancer pathogenesis. Hence, we aimed at identifying any potential association of CHOP 5'UTR-c.279T>C and +nt30C>T genotypes and corresponding haplotypes with overweight condition/pre-obesity and tumors/cancer in an Italian dataset.

5 citations

Journal ArticleDOI
TL;DR: Results revealed that the HOA-related matrilin-3 mutation (T298M) leads to a high expression level of growth arrest DNA damage-inducible gene 153 (GADD153, also known as CHOP; an endoplasmic reticulum stress marker) and does not significantly affect protein secretion, as shown by immunofluorescence staining.
Abstract: Mutations in matrilin-3 are associated with common skeletal diseases, such as hand osteoarthritis (HOA), as well as rare chondrodysplasias, such as multiple epiphyseal dysplasia (MED) and spondyloepimetaphyseal dysplasia (SEMD). In the present study, we constructed the mutations R116W [at the von Willebrand factor, type A (vWFA) domain], T298M [at the first epidermal growth factor (EGF) domain] and C299S (at the first EGF domain), according to the mouse sequence, which are associated with human MED, HOA and SEMD, respectively, by overlap extension PCR and inserted them into an expression vector (pcDNA3.1/v5-His). We transfected these contructs into the COS-1 or MCT cells, and the results revealed that the HOA-related matrilin-3 mutation (T298M) leads to a high expression level of growth arrest DNA damage-inducible gene 153 (GADD153, also known as CHOP; an endoplasmic reticulum stress marker), as shown by western blot analysis and does not significantly affect protein secretion, as shown by immunofluorescence staining; however, osteochondroplasia, i.e., MED-related (R116W) and SEMD-related (C299S) mutations lead to both high levels of GADD153 expression and protein trafficking into the cytoplasm and form multiple vacuoles in cells, which in turn leads to insufficient protein secretion.

5 citations

Journal Article
Jianfeng Zhang1, Junfeng Wu1, Weichen Zeng1, Yongfei Zhao1, Hengbing Zu1 
TL;DR: Endoplasmic reticulum stress might be involved in the apoptosis process of PC12 cell induced by Aβ25-35 and Ex-4 might provide a potential strategy for the treatment and prevention of cell apoptosis-associated disorders.
Abstract: Neurodegenerative disorders are chronic and progressive disease. Exendin-4 (Ex-4) can function as a neuroprotective agent and has novel therapeutic ability for the treatment of neurodegenerative disorders. In this study, we aimed to explore the neuroprotective effect of Ex-4 on PC12 cell apoptosis induced by Aβ25-35 in molecular level. The apoptosis of PC12 cells was detected by MTT assay, TUNEL staining and flow cytometry. The expression of ERS (endoplasmic reticulum stress, ERS) related proteins such as CHOP, GRP78 and Caspase-12 were determined by Western blot and cell immunocytochemistry. Results showed the apoptotic rate of PC12 cells significantly increased after Aβ25-35 addition, which was remarkably reduced after Ex-4 treatment. The expression of CHOP, GRP78 and Caspase-12 were significantly upregulated, and then remarkably reduced after Ex-4 treatment, while in the presence of Exendin9-39, the effect of Ex-4 was reversed. In conclusion, endoplasmic reticulum stress might be involved in the apoptosis process of PC12 cell induced by Aβ25-35 and Ex-4 might provide a potential strategy for the treatment and prevention of cell apoptosis-associated disorders.

5 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20213
20203
20193
201811
201719
201648