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      Heat Shock Protein 90 in Plants: Molecular Mechanisms and Roles in Stress Responses

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          Abstract

          The heat shock protein 90 (Hsp90) family mediates stress signal transduction, and plays important roles in the control of normal growth of human cells and in promoting development of tumor cells. Hsp90s have become a currently important subject in cellular immunity, signal transduction, and anti-cancer research. Studies on the physiological functions of Hsp90s began much later in plants than in animals and fungi. Significant progress has been made in understanding complex mechanisms of HSP90s in plants, including ATPase-coupled conformational changes and interactions with cochaperone proteins. A wide range of signaling proteins interact with HSP90s. Recent studies revealed that plant Hsp90s are important in plant development, environmental stress response, and disease and pest resistance. In this study, the plant HSP90 family was classified into three clusters on the basis of phylogenetic relationships, gene structure, and biological functions. We discuss the molecular functions of Hsp90s, and systematically review recent progress of Hsp90 research in plants.

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          The heat-shock response.

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            The function of heat-shock proteins in stress tolerance: degradation and reactivation of damaged proteins.

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              A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors.

              Heat shock protein 90 (Hsp90) is a molecular chaperone that plays a key role in the conformational maturation of oncogenic signalling proteins, including HER-2/ErbB2, Akt, Raf-1, Bcr-Abl and mutated p53. Hsp90 inhibitors bind to Hsp90, and induce the proteasomal degradation of Hsp90 client proteins. Although Hsp90 is highly expressed in most cells, Hsp90 inhibitors selectively kill cancer cells compared to normal cells, and the Hsp90 inhibitor 17-allylaminogeldanamycin (17-AAG) is currently in phase I clinical trials. However, the molecular basis of the tumour selectivity of Hsp90 inhibitors is unknown. Here we report that Hsp90 derived from tumour cells has a 100-fold higher binding affinity for 17-AAG than does Hsp90 from normal cells. Tumour Hsp90 is present entirely in multi-chaperone complexes with high ATPase activity, whereas Hsp90 from normal tissues is in a latent, uncomplexed state. In vitro reconstitution of chaperone complexes with Hsp90 resulted in increased binding affinity to 17-AAG, and increased ATPase activity. These results suggest that tumour cells contain Hsp90 complexes in an activated, high-affinity conformation that facilitates malignant progression, and that may represent a unique target for cancer therapeutics.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                Molecular Diversity Preservation International (MDPI)
                1422-0067
                2012
                23 November 2012
                : 13
                : 12
                : 15706-15723
                Affiliations
                Institute of Crop Science, Chinese Academy of Agricultural Sciences (CAAS)/National Key Facility for Crop Gene Resources and Genetic Improvement, Key Laboratory of Biology and Genetic Improvement of Triticeae Crops, Ministry of Agriculture, Beijing 100081, China; E-Mails: xuzhaoshi@ 123456yahoo.com.cn (Z.-S.X.); wangwangsd2010@ 123456yahoo.com.cn (Z.-Y.L.); chenyang712@ 123456126.com (Y.C.); chenming@ 123456mail.caas.net.cn (M.C.); lilch@ 123456mail.caas.net.cn (L.-C.L.)
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: mayouzhi@ 123456yahoo.com.cn ; Tel.: +86-10-6891-9718; Fax: +86-10-6891-8789.
                Article
                ijms-13-15706
                10.3390/ijms131215706
                3546657
                23443089
                1a0e3fff-1ec4-47f8-a9b3-6a7dc06a96ed
                © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 28 September 2012
                : 29 October 2012
                : 29 October 2012
                Categories
                Review

                Molecular biology
                interaction mechanism,plant hsp90,disease resistance,abiotic stress tolerance,phylogenetic relationship

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