Authors
Fortugno, PaolaBeltrami, Elena
Plescia, Janet
Fontana, Jason
Pradhan, Deepti
Marchisio, Pier Carlo
Sessa, William C.
Altieri, Dario C.
UMass Chan Affiliations
Department of Cancer Biology and Cancer CenterDocument Type
Journal ArticlePublication Date
2003-11-14Keywords
AnimalsApoptosis
Binding Sites
Cell Cycle
Cell Line
Cell Line, Tumor
Cell Survival
HSP90 Heat-Shock Proteins
Hela Cells
Humans
Macromolecular Substances
Mice
Microtubule-Associated Proteins
Mutagenesis, Site-Directed
Neoplasm Proteins
Protein Folding
Recombinant Proteins
Cancer Biology
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Pathways controlling cell proliferation and cell survival require flexible adaptation to environmental stresses. These mechanisms are frequently exploited in cancer, allowing tumor cells to thrive in unfavorable milieus. Here, we show that Hsp90, a molecular chaperone that is central to the cellular stress response, associates with survivin, an apoptosis inhibitor and essential regulator of mitosis. This interaction involves the ATPase domain of Hsp90 and the survivin baculovirus inhibitor of apoptosis repeat. Global suppression of the Hsp90 chaperone function or targeted Abmediated disruption of the survivin-Hsp90 complex results in proteasomal degradation of survivin, mitochondrial-dependent apoptosis, and cell cycle arrest with mitotic defects. These data link the cellular stress response to an antiapoptotic and mitotic checkpoint maintained by survivin. Targeting the survivin-Hsp90 complex may provide a rational approach for cancer therapy.Source
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13791-6. Epub 2003 Nov 12. Link to article on publisher's siteDOI
10.1073/pnas.2434345100Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38935PubMed ID
14614132Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1073/pnas.2434345100
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