The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Hsp60 Regulation of Tumor Cell Apoptosis
Open accessAbstract
Molecular chaperones may promote cell survival, but how this process is regulated, especially in cancer, is not well understood. Using high throughput proteomics screening, we identified the cell cycle regulator and apoptosis inhibitor survivin as a novel protein associated with the molecular chaperone Hsp60. Acute ablation of Hsp60 by small interfering RNA destabilizes the mitochondrial pool of survivin, induces mitochondrial dysfunction, and activates caspase-dependent apoptosis. This response involves disruption of an Hsp60-p53 complex, which results in p53 stabilization, increased expression of pro-apoptotic Bax, and Bax-dependent apoptosis. In vivo, Hsp60 is abundantly expressed in primary human tumors, as compared with matched normal tissues, and small interfering RNA ablation of Hsp60 in normal cells is well tolerated and does not cause apoptosis. Therefore, Hsp60 orchestrates a broad cell survival program centered on stabilization of mitochondrial survivin and restraining of p53 function, and this process is selectively exploited in cancer. Hsp60 inhibitors may function as attractive anticancer agents by differentially inducing apoptosis in tumor cells.
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Cited by
The mitochondrial UPR – protecting organelle protein homeostasis
Haynes, C. M., & Ron, D. (2010) · Journal of Cell Science · doi:10.1242/jcs.075119 · Cited by 494
Survivin and IAP proteins in cell-death mechanisms
Altieri, D. C. (2010) · Biochemical Journal · doi:10.1042/bj20100814 · Cited by 376
Self-citationSignaling the mitochondrial unfolded protein response
Pellegrino, M. W., Nargund, A. M., & Haynes, C. M. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.02.019 · Cited by 359
Bonora, M., & Pinton, P. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00302 · Cited by 208
Upadhyay, A., Dixit, U., Manvar, D., Chaturvedi, N., & Pandey, V. N. (2013) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.017020 · Cited by 36
Metadata
- Authors
- Ghosh, J. C., Dohi, T., Kang, B. H., & Altieri, D. C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 283
- Issue
- 8
- Pages
- 5188-5194
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2029690888
- Cited by
- 310
- References
- 43
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Ghosh, J. C., Dohi, T., Kang, B. H., & Altieri, D. C. (2008). Hsp60 Regulation of Tumor Cell Apoptosis. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m705904200
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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.
