Regulation of survivin function by Hsp90

Paola Fortugno, Elena Beltrami, Janet Plescia, Jason Fontana, Deepti Pradhan, Pier Carlo Marchisio, William C. Sessa, Dario C. Altieri

Research output: Contribution to journalArticle

270 Citations (Scopus)

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 Ab-mediated 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.

Original languageEnglish
Pages (from-to)13791-13796
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue numberSUPPL. 2
DOIs
Publication statusPublished - Nov 25 2003

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Apoptosis
M Phase Cell Cycle Checkpoints
Neoplasms
Molecular Chaperones
Baculoviridae
Cell Cycle Checkpoints
Mitosis
Adenosine Triphosphatases
Cell Survival
Cell Proliferation
Therapeutics

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Fortugno, P., Beltrami, E., Plescia, J., Fontana, J., Pradhan, D., Marchisio, P. C., ... Altieri, D. C. (2003). Regulation of survivin function by Hsp90. Proceedings of the National Academy of Sciences of the United States of America, 100(SUPPL. 2), 13791-13796. https://doi.org/10.1073/pnas.2434345100

Regulation of survivin function by Hsp90. / Fortugno, Paola; Beltrami, Elena; Plescia, Janet; Fontana, Jason; Pradhan, Deepti; Marchisio, Pier Carlo; Sessa, William C.; Altieri, Dario C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. SUPPL. 2, 25.11.2003, p. 13791-13796.

Research output: Contribution to journalArticle

Fortugno, P, Beltrami, E, Plescia, J, Fontana, J, Pradhan, D, Marchisio, PC, Sessa, WC & Altieri, DC 2003, 'Regulation of survivin function by Hsp90', Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. SUPPL. 2, pp. 13791-13796. https://doi.org/10.1073/pnas.2434345100
Fortugno P, Beltrami E, Plescia J, Fontana J, Pradhan D, Marchisio PC et al. Regulation of survivin function by Hsp90. Proceedings of the National Academy of Sciences of the United States of America. 2003 Nov 25;100(SUPPL. 2):13791-13796. https://doi.org/10.1073/pnas.2434345100
Fortugno, Paola ; Beltrami, Elena ; Plescia, Janet ; Fontana, Jason ; Pradhan, Deepti ; Marchisio, Pier Carlo ; Sessa, William C. ; Altieri, Dario C. / Regulation of survivin function by Hsp90. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. SUPPL. 2. pp. 13791-13796.
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