The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Bortezomib Inhibits PKR-Like Endoplasmic Reticulum (ER) Kinase and Induces Apoptosis via ER Stress in Human Pancreatic Cancer Cells
Abstract
Bortezomib (Velcade, formerly known as PS-341) is a boronic acid dipeptide derivative that is a selective and potent inhibitor of the proteasome. We hypothesized that proteasome inhibition would lead to an accumulation of misfolded proteins in the cell resulting in endoplasmic reticulum (ER) stress. The ability of bortezomib to induce ER stress and the unfolded protein response was investigated in a human pancreatic cancer cell line, L3.6pl. Bortezomib increased expression of ER stress markers, CHOP and BiP, but inhibited PKR-like ER kinase and subsequent phosphorylation of eukaryotic initiation factor 2α (eif2α), both of which are key events in translational suppression. These effects resulted in an accumulation of ubiquitylated proteins leading to protein aggregation and proteotoxicity. Peptide inhibitor or small interfering RNA targeting ER-resident caspase-4 blocked DNA fragmentation, establishing a central role for caspase-4 in bortezomib-induced cell death. The translation inhibitor cycloheximide abrogated bortezomib-induced protein aggregation, caspase-4 processing, and all other characteristics of apoptosis. Because malignant cells have higher protein synthesis rates than normal cells, they may be more prone to protein aggregation and proteotoxicity and possess increased sensitivity to bortezomib-induced apoptosis. Taken together, the results show that bortezomib induces a unique type of ER stress compared with other ER stress agents characterized by an absence of eif2α phosphorylation, ubiquitylated protein accumulation, and proteotoxicity. (Cancer Res 2005; 65(24): 11510-9)
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Nicoletti, I., Migliorati, G., Pagliacci, M. C., Grignani, F., & Riccardi, C. (1991) · Journal of Immunological Methods · doi:10.1016/0022-1759(91)90198-o · Cited by 4,579
The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction
Glickman, M. H., & Ciechanover, A. (2002) · Physiological Reviews · doi:10.1152/physrev.00027.2001 · Cited by 4,237
A Phase 2 Study of Bortezomib in Relapsed, Refractory Myeloma
Richardson, P. G., Barlogie, B., Berenson, J., Singhal, S., Jagannath, S., Irwin, D., Rajkumar, S. V., Srkalovic, G., Alsina, M., Alexanian, R., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa030288 · Cited by 2,632
Kaufman, R. J. (1999) · Genes & Development · doi:10.1101/gad.13.10.1211 · Cited by 2,248
Quality control in the endoplasmic reticulum
Ellgaard, L., & Helenius, A. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1052 · Cited by 2,126
Harding, H. P., Zhang, Y., Bertolotti, A., Zeng, H., & Ron, D. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80330-5 · Cited by 2,021
Travers, K. J., Patil, C. K., Wodicka, L., Lockhart, D. J., Weissman, J. S., & Walter, P. (2000) · Cell · doi:10.1016/s0092-8674(00)80835-1 · Cited by 1,992
Aggresomes, inclusion bodies and protein aggregation
Kopito, R. R. (2000) · Trends in Cell Biology · doi:10.1016/s0962-8924(00)01852-3 · Cited by 1,921
Hideshima, T., Richardson, P. G. G., Chauhan, D., Palombella, V. J., Elliott, P. J., Adams, J., & Anderson, K. C. (2001) · PubMed · Cited by 1,508
Proteasome inhibitors: a novel class of potent and effective antitumor agents.
Adams, J., Palombella, V. J., Sausville, E. A., Johnson, J. I., Destree, A. T., Lazarus, D. D., Maas, J., Pien, C. S., Prakash, S., & Elliott, P. J. (1999) · PubMed · Cited by 1,477
Cited by
The impact of the unfolded protein response on human disease
Wang, S., & Kaufman, R. J. (2012) · Journal of Cell Biology · doi:10.1083/jcb.201110131 · Cited by 984
Ding, W.-X., Ni, H.-M., Gao, W., Yoshimori, T., Stolz, D. B., Ron, D., & Yin, X.-M. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.070188 · Cited by 708
Neubert, K., Meister, S., Moser, K., Weisel, F., Maseda, D., Amann, K., Wiethe, C., Winkler, T. H., Kalden, J. R., Manz, R. A., et al. (2008) · Nature Medicine · doi:10.1038/nm1763 · Cited by 584
Proteasome Inhibitors in Cancer Therapy: Lessons from the First Decade
Orlowski, R. Z., & Kuhn, D. J. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-2218 · Cited by 578
Histone deacetylase inhibitors: Mechanisms of cell death and promise in combination cancer therapy
Carew, J. S., Giles, F. J., & Nawrocki, S. T. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.03.037 · Cited by 421
Self-citation
Metadata
- Authors
- Nawrocki, S. T., Carew, J. S., Dunner, K., Boise, L. H., Chiao, P. J., Huang, P., Abbruzzese, J. L., & McConkey, D. J.
- Venue
- Cancer Research
- Published
- 2005-12-15
- Volume
- 65
- Issue
- 24
- Pages
- 11510-11519
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2113915760
- Cited by
- 324
- References
- 52
- FWCI
- 7.05
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Bortezomib Inhibits PKR-Like Endoplasmic Reticulum (ER) Kinase and Induces Apoptosis via ER Stress in Human Pancreatic Cancer Cells. https://app.cochat.ai/papers/10.1158/0008-5472.can-05-2394
- The paper
- Nawrocki, S. T., Carew, J. S., Dunner, K., Boise, L. H., Chiao, P. J., Huang, P., Abbruzzese, J. L., & McConkey, D. J. (2005). Bortezomib Inhibits PKR-Like Endoplasmic Reticulum (ER) Kinase and Induces Apoptosis via ER Stress in Human Pancreatic Cancer Cells. Cancer Research. https://doi.org/10.1158/0008-5472.can-05-2394
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
