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http://dx.doi.org/10.4062/biomolther.2019.051

Traditional and Novel Mechanisms of Heat Shock Protein 90 (HSP90) Inhibition in Cancer Chemotherapy Including HSP90 Cleavage  

Park, Sangkyu (Department of Biochemistry, College of Natural Sciences, Chungbuk National University)
Park, Jeong-A (Department of Biochemistry, College of Natural Sciences, Chungbuk National University)
Jeon, Jae-Hyung (Department of Biochemistry, College of Natural Sciences, Chungbuk National University)
Lee, Younghee (Department of Biochemistry, College of Natural Sciences, Chungbuk National University)
Publication Information
Biomolecules & Therapeutics / v.27, no.5, 2019 , pp. 423-434 More about this Journal
Abstract
HSP90 is a molecular chaperone that increases the stability of client proteins. Cancer cells show higher HSP90 expression than normal cells because many client proteins play an important role in the growth and survival of cancer cells. HSP90 inhibitors mainly bind to the ATP binding site of HSP90 and inhibit HSP90 activity, and these inhibitors can be distinguished as ansamycin and non-ansamycin depending on the structure. In addition, the histone deacetylase inhibitors inhibit the activity of HSP90 through acetylation of HSP90. These HSP90 inhibitors have undergone or are undergoing clinical trials for the treatment of cancer. On the other hand, recent studies have reported that various reagents induce cleavage of HSP90, resulting in reduced HSP90 client proteins and growth suppression in cancer cells. Cleavage of HSP90 can be divided into enzymatic cleavage and non-enzymatic cleavage. Therefore, reagents inducing cleavage of HSP90 can be classified as another class of HSP90 inhibitors. We discuss that the cleavage of HSP90 can be another mechanism in the cancer treatment by HSP90 inhibition.
Keywords
HSP90 inhibitors; Anti-cancer therapy; ATP binding; Acetylation; HSP90 cleavage;
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