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dc.contributor.authorGhosh, Jagadish C.
dc.contributor.authorDohi, Takehiko
dc.contributor.authorKang, Byoung
dc.contributor.authorAltieri, Dario C.
dc.date2022-08-11T08:09:37.000
dc.date.accessioned2022-08-23T16:37:52Z
dc.date.available2022-08-23T16:37:52Z
dc.date.issued2007-12-19
dc.date.submitted2009-10-22
dc.identifier.citationJ Biol Chem. 2008 Feb 22;283(8):5188-94. Epub 2007 Dec 17. <a href="http://dx.doi.org/10.1074/jbc.M705904200">Link to article on publisher's site</a>
dc.identifier.issn0021-9258 (Print)
dc.identifier.doi10.1074/jbc.M705904200
dc.identifier.pmid18086682
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39121
dc.description.abstractMolecular 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=18086682&dopt=Abstract">Link to Article in PubMed</a>
dc.subject*Apoptosis
dc.subjectCaspases
dc.subject*Cell Cycle
dc.subjectCell Line, Tumor
dc.subjectCell Survival
dc.subjectChaperonin 60
dc.subjectFemale
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectHumans
dc.subjectMicrotubule-Associated Proteins
dc.subjectMitochondria
dc.subjectNeoplasm Proteins
dc.subjectNeoplasms
dc.subjectProteomics
dc.subjectRNA, Small Interfering
dc.subjectTumor Suppressor Protein p53
dc.subjectbcl-2-Associated X Protein
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleHsp60 regulation of tumor cell apoptosis
dc.typeArticle
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume283
dc.source.issue8
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2935&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1936
dc.identifier.contextkey1042865
refterms.dateFOA2022-08-23T16:37:52Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/1936
dc.contributor.departmentDepartment of Cancer Biology and the Cancer Center
dc.source.pages5188-94


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