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热休克蛋白90β亚型:药物研发的一个有吸引力的靶点。

The Hsp90β Isoform: An Attractive Target for Drug Development.

作者信息

Chaudhury Subhabrata, D'Amico Terin, Blagg Brian S J

机构信息

Department of Chemistry and Biochemistry, Warren Family Research Center for Drug Discovery and Development, University of Notre Dame, Notre Dame, Indiana, USA.

Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.

出版信息

Med Res Rev. 2025 Sep;45(5):1452-1465. doi: 10.1002/med.22114. Epub 2025 Apr 28.

Abstract

The beta isoform of 90 kDa heat shock protein (Hsp90β) plays a critical role in maintaining cellular proteostasis by assisting in the folding and refolding of proteins, which is essential for both normal cellular function and stress response. It is constitutively expressed in mammalian cells, differentiating it from the inducible Hsp90α isoform. Hsp90β's involvement in diverse cellular processes, such as signal transduction, cell cycle control, and apoptosis, underscores its significant role in various diseases, including cancer and neurodegenerative disorders. The isoform-specific functions of Hsp90β and its interaction with unique client proteins make it a promising target for therapeutic intervention, particularly in the development of selective inhibitors that avoid the adverse effects observed with pan-Hsp90 inhibitors. This review delves into the structural and functional intricacies of Hsp90β, its role in disease, and the potential for selective drug development.

摘要

90 kDa热休克蛋白(Hsp90β)的β亚型在维持细胞蛋白质稳态中起着关键作用,它通过协助蛋白质的折叠和重新折叠来实现,这对于正常细胞功能和应激反应都至关重要。它在哺乳动物细胞中组成性表达,这使其与可诱导的Hsp90α亚型有所不同。Hsp90β参与多种细胞过程,如信号转导、细胞周期控制和细胞凋亡,这突出了其在包括癌症和神经退行性疾病在内的各种疾病中的重要作用。Hsp90β的亚型特异性功能及其与独特客户蛋白的相互作用使其成为治疗干预的一个有前景的靶点,特别是在开发避免泛Hsp90抑制剂所观察到的不良反应的选择性抑制剂方面。本综述深入探讨了Hsp90β的结构和功能复杂性、其在疾病中的作用以及选择性药物开发的潜力。

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