Review
Approaches for defining the Hsp90-dependent proteome

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Abstract

Hsp90 is the target of ongoing drug discovery studies seeking new compounds to treat cancer, neurodegenerative diseases, and protein folding disorders. To better understand Hsp90's roles in cellular pathologies and in normal cells, numerous studies have utilized proteomics assays and related high-throughput tools to characterize its physical and functional protein partnerships. This review surveys these studies, and summarizes the strengths and limitations of the individual attacks. We also include downloadable spreadsheets compiling all of the Hsp90-interacting proteins identified in more than 23 studies. These tools include cross-references among gene aliases, human homologues of yeast Hsp90-interacting proteins, hyperlinks to database entries, summaries of canonical pathways that are enriched in the Hsp90 interactome, and additional bioinformatic annotations. In addition to summarizing Hsp90 proteomics studies performed to date and the insights they have provided, we identify gaps in our current understanding of Hsp90-mediated proteostasis. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90).

Highlights

► Summary of findings from past proteomic studies examining the Hsp90-interactome. ► Critical assessment of methodologies used in past Hsp90 proteomic studies. ► Discussion of new insights gained from proteomic studies into Hsp90 function. ► Future perspectives on studies of Hsp90 proteomics: reaching the next level.

Keywords

Hsp90-interactome
Proteomics
LC–MS/MS
High-throughput screen
Hsp90 inhibitor

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This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90).