Hsp60 regulation of tumor cell apoptosis

Jagadish C. Ghosh, Takehiko Dohi, Heon Kang Byoung, Dario C. Altieri

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5188-5194
Number of pages7
JournalJournal of Biological Chemistry
Volume283
Issue number8
DOIs
StatePublished - Feb 22 2008

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Tumors
Cells
Apoptosis
Molecular Chaperones
Neoplasms
Ablation
Small Interfering RNA
Cell Survival
Stabilization
Caspases
Antineoplastic Agents
Proteomics
Cell Cycle
Screening
Throughput
Tissue
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ghosh, Jagadish C. ; Dohi, Takehiko ; Byoung, Heon Kang ; Altieri, Dario C. / Hsp60 regulation of tumor cell apoptosis. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 8. pp. 5188-5194.
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Ghosh, JC, Dohi, T, Byoung, HK & Altieri, DC 2008, 'Hsp60 regulation of tumor cell apoptosis', Journal of Biological Chemistry, vol. 283, no. 8, pp. 5188-5194. https://doi.org/10.1074/jbc.M705904200

Hsp60 regulation of tumor cell apoptosis. / Ghosh, Jagadish C.; Dohi, Takehiko; Byoung, Heon Kang; Altieri, Dario C.

In: Journal of Biological Chemistry, Vol. 283, No. 8, 22.02.2008, p. 5188-5194.

Research output: Contribution to journalArticle

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