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Kang, Byoung Heon
Cancer Biology Lab
Research Interests
  • Mitochondrial chaperones, cancer biology, cell death, metabolism, cancer stem cells, cancer therapeutics development

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Hsp60 regulation of tumor cell apoptosis

Cited 80 times inthomson ciCited 79 times inthomson ci
Title
Hsp60 regulation of tumor cell apoptosis
Author
Ghosh, Jagadish C.Dohi, TakehikoKang, Byoung HeonAltieri, Dario C.
Issue Date
2008-02
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.283, no.8, pp.5188 - 5194
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.
URI
https://scholarworks.unist.ac.kr/handle/201301/7110
URL
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=41949125351
DOI
10.1074/jbc.M705904200
ISSN
0021-9258
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BIO_Journal Papers
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