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HSP90 protects apoptotic cleavage of vimentin in geldanamycin-induced apoptosis

Title
HSP90 protects apoptotic cleavage of vimentin in geldanamycin-induced apoptosis
Authors
Zhang M.-H.Lee J.-S.Kim H.-J.Jin D.-I.Kim J.-I.Lee K.-J.Seo J.-S.
Ewha Authors
이공주김희정
SCOPUS Author ID
이공주scopus; 김희정scopusscopusscopus
Issue Date
2006
Journal Title
Molecular and Cellular Biochemistry
ISSN
0300-8177JCR Link
Citation
Molecular and Cellular Biochemistry vol. 281, no. 1-2, pp. 111 - 121
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Heat shock protein (HSP) 90 is of interest as an anticancer drug target because of its importance in maintaining the conformation, stability and function of the client proteins involved in signal transduction pathways leading to proliferation, cell cycle progression, and apoptosis. Geldanamycin, a specific antagonist of HSP90, binds directly to HSP90 and promotes proteolytic degradation of client proteins of HSP90. The aim of the present study was to identify novel client proteins of HSP90 and to elucidate HSP90 function through inhibition of HSP90 binding to its client proteins, by using of geldanamycin. We investigated changes in protein profile when apoptosis was induced by exposure to geldanamycin. Differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), in human neuroblastoma SK-N-SH cells. The vimentin level was found to decrease dramatically by the treatment of geldanamycin. We observed subcellular co-localization of vimentin and HSP90. Physical association of vimentin with HSP90 was detected by an immunoprecipitation assay. The caspase inhibitors, Z-VAD-FMK and Ac-DEVD-CHO, completely abolished geldanamycin-induced cleavage of vimentin. Changes of HSP90 level by antisense treatment or transfection of HSP90-overexpressing vector affected geldanamycin-induced cleavage of vimentin. These results suggest that HSP90 protects vimentin by physical interaction in the geldanamycin-induced apoptotic pathway. © Springer Science + Business Media, Inc. 2006.
DOI
10.1007/s11010-006-0638-x
Appears in Collections:
약학대학 > 약학과 > Journal papers
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