The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
ER Stress Triggers Apoptosis by Activating BH3-Only Protein Bim
Open accessAbstract
Endoplasmic reticulum (ER) stress caused by misfolded proteins or cytotoxic drugs can kill cells and although activation of this pathway has been implicated in the etiology of certain degenerative disorders its mechanism remains unresolved. Bim, a proapoptotic BH3-only member of the Bcl-2 family is required for initiation of apoptosis induced by cytokine deprivation or certain stress stimuli. Its proapoptotic activity can be regulated by several transcriptional or posttranslational mechanisms, such as ERK-mediated phosphorylation, promoting its ubiquitination and proteasomal degradation. We found that Bim is essential for ER stress-induced apoptosis in a diverse range of cell types both in culture and within the whole animal. ER stress activates Bim through two novel pathways, involving protein phosphatase 2A-mediated dephosphorylation, which prevents its ubiquitination and proteasomal degradation and CHOP-C/EBPalpha-mediated direct transcriptional induction. These results define the molecular mechanisms of ER stress-induced apoptosis and identify targets for therapeutic intervention in ER stress-related diseases.
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Cites
p53- and Drug-Induced Apoptotic Responses Mediated by BH3-Only Proteins Puma and Noxa
Villunger, A., Michalak, E. M., Coultas, L., Müllauer, F., Böck, G., Ausserlechner, M. J., Adams, J. M., & Strasser, A. (2003) · Science · doi:10.1126/science.1090072 · Cited by 1,327
Self-citationOrchestrating the unfolded protein response in health and disease
Kaufman, R. J. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0216886 · Cited by 1,015
BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes
Bouillet, P., Purton, J. F., Godfrey, D. I., Zhang, L.-C., Coultas, L., Puthalakath, H., Pellegrini, M., Cory, S., Adams, J. M., & Strasser, A. (2002) · Nature · doi:10.1038/415922a · Cited by 782
Self-citationPuthalakath, H., Villunger, A., O'Reilly, L. A., Beaumont, J. G., Coultas, L., Cheney, R. E., Huang, D. C. S., & Strasser, A. (2001) · Science · doi:10.1126/science.1062257 · Cited by 656
Self-citationThe PP2A-Associated Protein α4 Is an Essential Inhibitor of Apoptosis
Kong, M., Fox, C. J., Mu, J., Solt, L., Xu, A., Cinalli, R. M., Birnbaum, M. J., Lindsten, T., & Thompson, C. B. (2004) · Science · doi:10.1126/science.1100537 · Cited by 149
Cited by
The integrated stress response
Pakos‐Zebrucka, K., Koryga, I., Mnich, K., Ljujic, M., Samali, A., & Gorman, A. M. (2016) · The EMBO Reports · doi:10.15252/embr.201642195 · Cited by 2,659
Mechanisms, regulation and functions of the unfolded protein response
Hetz, C., Zhang, K., & Kaufman, R. J. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0250-z · Cited by 2,666
From endoplasmic-reticulum stress to the inflammatory response
Zhang, K., & Kaufman, R. J. (2008) · Nature · doi:10.1038/nature07203 · Cited by 2,010
ER stress-induced cell death mechanisms
Sano, R., & Reed, J. C. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.06.028 · Cited by 1,988
ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death
Han, J., Back, S. H., Hur, J., Lin, Y.-H., Gildersleeve, R., Shan, J., Yuan, C. L., Krokowski, D., Wang, S., Hatzoglou, M., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2738 · Cited by 1,691
Metadata
- Authors
- Puthalakath, H., O'Reilly, L. A., Gunn, P., Lee, L., Kelly, P. N., Huntington, N. D., Hughes, P. D., Michalak, E. M., McKimm-Breschkin, J., Motoyama, N., Gotoh, T., Akira, S., Bouillet, P., & Strasser, A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 129
- Issue
- 7
- Pages
- 1337-1349
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2012166934
- Cited by
- 1,425
- References
- 5
- FWCI
- 27.14
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Puthalakath, H., O'Reilly, L. A., Gunn, P., Lee, L., Kelly, P. N., Huntington, N. D., Hughes, P. D., Michalak, E. M., McKimm-Breschkin, J., Motoyama, N., Gotoh, T., Akira, S., Bouillet, P., & Strasser, A. (2007). ER Stress Triggers Apoptosis by Activating BH3-Only Protein Bim. Cell. https://doi.org/10.1016/j.cell.2007.04.027
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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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