eprintid: 19806
rev_number: 23
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dir: disk0/00/01/98/06
datestamp: 2013-10-09 16:04:24
lastmod: 2019-02-02 16:58:26
status_changed: 2013-10-09 16:04:24
type: article
metadata_visibility: show
item_issues_count: 0
eprint_status: archive
creators_name: Rodina, A
creators_name: Vilenchik, M
creators_name: Moulick, K
creators_name: Aguirre, J
creators_name: Kim, J
creators_name: Chiang, A
creators_name: Litz, J
creators_name: Clement, CC
creators_name: Kang, Y
creators_name: She, Y
creators_name: Wu, N
creators_name: Felts, S
creators_name: Wipf, P
creators_name: Massague, J
creators_name: Jiang, X
creators_name: Brodsky, JL
creators_name: Krystal, GW
creators_name: Chiosis, G
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creators_email: jbrodsky@pitt.edu
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title: Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer
ispublished: pub
divisions: sch_as_chemistry
full_text_status: public
abstract: The heat shock protein 90 (Hsp90) has a critical role in malignant transformation. Whereas its ability to maintain the functional conformations of mutant and aberrant oncoproteins is established, a transformation-specific regulation of the antiapoptotic phenotype by Hsp90 is poorly understood. By using selective compounds, we have discovered that small-cell lung carcinoma is a distinctive cellular system in which apoptosis is mainly regulated by Hsp90. Unlike the well-characterized antiapoptotic chaperone Hsp70, Hsp90 is not a general inhibitor of apoptosis, but it assumes this role in systems such as small-cell lung carcinoma, in which apoptosis is uniquely dependent on and effected through the intrinsic pathway, without involvement of caspase elements upstream of mitochondria or alternate pathways that are not apoptosome- channeled. These results provide important evidence for a transformation- specific interplay between chaperones in regulating apoptosis in malignant cells. © 2007 Nature Publishing Group.
date: 2007-01-01
date_type: published
publication: Nature Chemical Biology
volume: 3
number: 8
pagerange: 498 - 507
refereed: TRUE
issn: 1552-4450
id_number: 10.1038/nchembio.2007.10
pmid: 17603540
mesh_headings: Antineoplastic Agents--pharmacology
mesh_headings: Apoptosis
mesh_headings: Carcinoma, Small Cell--drug therapy
mesh_headings: Carcinoma, Small Cell--metabolism
mesh_headings: Carcinoma, Small Cell--pathology
mesh_headings: Cell Line, Tumor
mesh_headings: Cell Transformation, Neoplastic
mesh_headings: Dose-Response Relationship, Drug
mesh_headings: Drug Design
mesh_headings: Drug Screening Assays, Antitumor
mesh_headings: Gene Expression Regulation, Neoplastic
mesh_headings: HSP90 Heat-Shock Proteins--metabolism
mesh_headings: Humans
mesh_headings: Lung Neoplasms--drug therapy
mesh_headings: Lung Neoplasms--metabolism
mesh_headings: Lung Neoplasms--pathology
mesh_headings: Models, Chemical
mesh_headings: Phosphatidylinositol 3-Kinases--metabolism
mesh_headings: Time Factors
chemical_names: Antineoplastic Agents
chemical_names: HSP90 Heat-Shock Proteins
chemical_names: Phosphatidylinositol 3-Kinases
citation:   Rodina, A and Vilenchik, M and Moulick, K and Aguirre, J and Kim, J and Chiang, A and Litz, J and Clement, CC and Kang, Y and She, Y and Wu, N and Felts, S and Wipf, P and Massague, J and Jiang, X and Brodsky, JL and Krystal, GW and Chiosis, G  (2007) Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer.  Nature Chemical Biology, 3 (8).  498 - 507.  ISSN 1552-4450     
document_url: http://d-scholarship-dev.library.pitt.edu/19806/1/licence.txt