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Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer

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

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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.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Rodina, A
Vilenchik, M
Moulick, K
Aguirre, J
Kim, J
Chiang, A
Litz, J
Clement, CC
Kang, Y
She, Y
Wu, N
Felts, S
Wipf, Ppwipf@pitt.eduPWIPF
Massague, J
Jiang, X
Brodsky, JLjbrodsky@pitt.eduJBRODSKY0000-0002-6984-8486
Krystal, GW
Chiosis, G
Date: 1 January 2007
Date Type: Publication
Journal or Publication Title: Nature Chemical Biology
Volume: 3
Number: 8
Page Range: 498 - 507
DOI or Unique Handle: 10.1038/nchembio.2007.10
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 1552-4450
MeSH Headings: Antineoplastic Agents--pharmacology; Apoptosis; Carcinoma, Small Cell--drug therapy; Carcinoma, Small Cell--metabolism; Carcinoma, Small Cell--pathology; Cell Line, Tumor; Cell Transformation, Neoplastic; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Gene Expression Regulation, Neoplastic; HSP90 Heat-Shock Proteins--metabolism; Humans; Lung Neoplasms--drug therapy; Lung Neoplasms--metabolism; Lung Neoplasms--pathology; Models, Chemical; Phosphatidylinositol 3-Kinases--metabolism; Time Factors
PubMed ID: 17603540
Date Deposited: 09 Oct 2013 16:04
Last Modified: 02 Feb 2019 16:58
URI: http://d-scholarship.pitt.edu/id/eprint/19806

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