UMMS Affiliation

Department of Cancer Biology and Cancer Center

Publication Date

11-14-2003

Document Type

Article

Subjects

Animals; Apoptosis; 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

Disciplines

Cancer Biology | Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13791-6. Epub 2003 Nov 12. Link to article on publisher's site

DOI of Published Version

10.1073/pnas.2434345100

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

14614132

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