The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
CHOP Is Involved in Endoplasmic Reticulum Stress-induced Apoptosis by Enhancing DR5 Expression in Human Carcinoma Cells
Open accessAbstract
It has been shown that excess stress to the endoplasmic reticulum (ER) triggers apoptosis, but the mechanisms underlying these processes remain unclear. We and others have reported previously that DR5 expression is up-regulated in thapsigargin (THG)-treated human cancer cells. Here, we provide evidence that CHOP is involved in THG up-regulation of DR5, which is a critical step for ER stress-induced apoptosis in human cancer cells. In human colon cancer HCT116 cells, knockdown of DR5 by siRNA blocked THG-induced Bax conformational change along with caspase-3 activation and cell death. Moreover, inhibition of CHOP expression attenuated DR5 up-regulation and apoptosis induced by THG, whereas ectopic expression of DR5 restored the sensitivity of CHOP siRNA-transfected cells to THG-induced apoptosis. In addition to HCT116 cells, inhibition of CHOP or DR5 induction also attenuated THG-induced cell death in other cancer cell lines including LNCaP, A2780S, and DU145, indicating that CHOP and DR5 are critical for ER stress-mediated apoptosis in human carcinoma cells. Furthermore, we identified a potential CHOP-binding site in the 5'-flanking region of the DR5 gene. Mutation of this site abrogated the enhanced reporter activity in response to THG treatment. Together, our findings suggest that CHOP regulates ER stress-induced apoptosis, at least in part, through enhancing DR5 expression in some types of human cancer cells.
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Cites
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From endoplasmic-reticulum stress to the inflammatory response
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ER stress-induced cell death mechanisms
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The Role for Endoplasmic Reticulum Stress in Diabetes Mellitus
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Endoplasmic reticulum stress signalling-from basic mechanisms to clinical applications
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Metadata
- Authors
- Yamaguchi, H., & Wang, H.-G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-10
- Volume
- 279
- Issue
- 44
- Pages
- 45495-45502
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1965727325
- Cited by
- 831
- References
- 32
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Yamaguchi, H., & Wang, H.-G. (2004). CHOP Is Involved in Endoplasmic Reticulum Stress-induced Apoptosis by Enhancing DR5 Expression in Human Carcinoma Cells. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m406933200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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