Abstract
ABSTRACTHeat-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.
Highlights
ED Proteins facilitate diverse cellular processes, such as metabolism, the electron transport IT chain, and movement of organelles
U Here, we review tools and techniques for Heat-shock protein 90 (Hsp90) network mapping available in different fungi N and provide a summary of existing mapping efforts
Cerevisiae screen to date, combining Y2H, that of RItandem affinity purification (TAP)-mass spectrometry (MS), Synthetic genetic arrays (SGA), and chemical genetic synthetic lethality (CGSL) screens, showed that at 30 ̊C >10% of interactors function in transcription, cellular fate, protein post-translational modifications, metabolism, cellular transport, and the cell cycle and DNA processing (Zhao et al 2005)
Summary
ED Proteins facilitate diverse cellular processes, such as metabolism, the electron transport IT chain, and movement of organelles. To get a global view of the genes and proteins that either directly or indirectly interact with Hsp, a suite of genetic and molecular biological manipulations is required These include genome-scale collections of loss-of-function mutants and epitope-tagged strains. Cerevisiae screen to date, combining Y2H, TAP-MS, SGA, and CGSL screens, showed that at 30 ̊C >10% of interactors function in transcription, cellular fate, protein post-translational modifications, metabolism, cellular transport, and the cell cycle and DNA processing (Zhao et al 2005) This finding was supported by a CGSL screen comparing Hsp genetic. L To reveal more detail of Hsp90‘s role as a regulator of virulence traits in C. albicans, A the Hsp genetic interaction network was mapped using the transposon insertion mutant library (Davis et al 2002). To U fully understand the degree of divergence between Hsp chaperone networks in different L species, network assays need to be done under comparable conditions
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