School of Cellular and Molecular Medicine, University of Bristol, University Walk, Bristol BS8 1TD, UK.
FEMS Yeast Res. 2021 Nov 16;21(7). doi: 10.1093/femsyr/foab054.
Heat-shock protein 90 (Hsp90) is a central regulator of cellular proteostasis. It stabilizes numerous proteins that are involved in fundamental processes of life, including cell growth, cell-cycle progression and the environmental response. In addition to stabilizing proteins, Hsp90 governs gene expression and controls the release of cryptic genetic variation. Given its central role in evolution and development, it is important to identify proteins and genes that interact with Hsp90. This requires sophisticated genetic and biochemical tools, including extensive mutant collections, suitable epitope tags, proteomics approaches and Hsp90-specific pharmacological inhibitors for chemogenomic screens. These usually only exist in model organisms, such as the yeast Saccharomyces cerevisiae. Yet, the importance of other fungal species, such as Candida albicans and Cryptococcus neoformans, as serious human pathogens accelerated the development of genetic tools to study their virulence and stress response pathways. These tools can also be exploited to map Hsp90 interaction networks. Here, we review tools and techniques for Hsp90 network mapping available in different fungi and provide a summary of existing mapping efforts. Mapping Hsp90 networks in fungal species spanning >500 million years of evolution provides a unique vantage point, allowing tracking of the evolutionary history of eukaryotic Hsp90 networks.
热休克蛋白 90(Hsp90)是细胞蛋白稳态的核心调节剂。它稳定了许多参与生命基本过程的蛋白质,包括细胞生长、细胞周期进程和环境反应。除了稳定蛋白质外,Hsp90还控制基因表达并控制隐藏遗传变异的释放。鉴于其在进化和发育中的核心作用,识别与 Hsp90 相互作用的蛋白质和基因非常重要。这需要复杂的遗传和生化工具,包括广泛的突变体集合、合适的表位标签、蛋白质组学方法和 Hsp90 特异性药理学抑制剂,用于化学基因组筛选。这些通常仅存在于模式生物中,如酵母酿酒酵母。然而,其他真菌物种(如白色念珠菌和新型隐球菌)作为严重的人类病原体的重要性加速了研究其毒力和应激反应途径的遗传工具的发展。这些工具也可用于绘制 Hsp90 相互作用网络。在这里,我们回顾了不同真菌中用于 Hsp90 网络映射的工具和技术,并提供了现有映射工作的摘要。在跨越 5 亿多年进化的真菌物种中绘制 Hsp90 网络提供了一个独特的视角,允许追踪真核 Hsp90 网络的进化历史。