Hsp90 Co-chaperones Form Plastic Genetic Networks Adapted to Client Maturation

Biebl, Matthias; Riedl, Maximilian; Büchner, Johannes

doi:10.1016/j.celrep.2020.108063

Cited by 31 publications

(20 citation statements)

References 118 publications

(177 reference statements)

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“…The number and types of Hsp90 cochaperones varies from species to species, suggesting a correlation between client diversity and the range of available cochaperones (Johnson and Brown 2009). Analysis of yeast cochaperones suggests that a few cochaperones are required for core Hsp90 functions, while others have more specialized functions (Biebl et al 2020;Sahasrabudhe et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Human Hsp90 cochaperones: perspectives on tissue-specific expression and identification of cochaperones with similar in vivo functions

Dean

Johnson

2021

Cell Stress and Chaperones

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The Hsp90 molecular chaperone is required for the function of hundreds of different cellular proteins. Hsp90 and a cohort of interacting proteins called cochaperones interact with clients in an ATP-dependent cycle. Cochaperone functions include targeting clients to Hsp90, regulating Hsp90 ATPase activity, and/or promoting Hsp90 conformational changes as it progresses through the cycle. Over the last 20 years, the list of cochaperones identified in human cells has grown from the initial six identified in complex with steroid hormone receptors and protein kinases to about fifty different cochaperones found in Hsp90-client complexes. These cochaperones may be placed into three groups based on shared Hsp90 interaction domains. Available evidence indicates that cochaperones vary in client specificity, abundance, and tissue distribution. Many of the cochaperones have critical roles in regulation of cancer and neurodegeneration. A more limited set of cochaperones have cellular functions that may be limited to tissues such as muscle and testis. It is likely that a small set of cochaperones are part of the core Hsp90 machinery required for the folding of a wide range of clients. The presence of more selective cochaperones may allow greater control of Hsp90 activities across different tissues or during development.

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Section: Discussionmentioning

confidence: 99%

Human Hsp90 cochaperones: perspectives on tissue-specific expression and identification of cochaperones with similar in vivo functions

Dean

Johnson

2021

Cell Stress and Chaperones

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“…Protein kinases use ATP as a donor to attach phosphate groups to substrate proteins a key mechanism for transducing signals that regulate progression through the cell cycle, for differentiation, for responses to cell stimuli such as stress and many more processes. Hop binds to Hsp90 in a mechanism mutually exclusive of Cdc37 (Siligardi et al 2002), although Hop and Hsp70 may in themselves aid kinase folding and maturation along a parallel process (Biebl et al 2020). The conserved dual lobe ATP-binding clefts characteristic of many kinase domains are structurally unstable and require Cdc37 to load them on to Hsp90 in order to be folded (Verba et al 2016).…”

Section: The Hsp90 Chaperone Machinementioning

confidence: 99%

The functions and regulation of heat shock proteins; key orchestrators of proteostasis and the heat shock response

et al. 2021

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Cells respond to protein-damaging (proteotoxic) stress by activation of the Heat Shock Response (HSR). The HSR provides cells with an enhanced ability to endure proteotoxic insults and plays a crucial role in determining subsequent cell death or survival. The HSR is, therefore, a critical factor that influences the toxicity of protein stress. While named for its vital role in the cellular response to heat stress, various components of the HSR system and the molecular chaperone network execute essential physiological functions as well as responses to other diverse toxic insults. The effector molecules of the HSR, the Heat Shock Factors (HSFs) and Heat Shock Proteins (HSPs), are also important regulatory targets in the progression of neurodegenerative diseases and cancers. Modulation of the HSR and/or its extended network have, therefore, become attractive treatment strategies for these diseases. Development of effective therapies will, however, require a detailed understanding of the HSR, important features of which continue to be uncovered and are yet to be completely understood. We review recently described and hallmark mechanistic principles of the HSR, the regulation and functions of HSPs, and contexts in which the HSR is activated and influences cell fate in response to various toxic conditions.

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“…Different co-chaperones facilitate unique functions of Hsp90, thereby influencing its selection of clients. The Hsp90 protein associates with a variety of cytosolic co-chaperones illustrated in Table 1 [49]. Peptidylprolyl-cis/trans-isomerase [62,63] PfCns1 (PF3D7_1108900) [48] The co-chaperone gene names with PlasmoDB accession numbers and functions are shown with the abbreviated protein names are as follows: FKBP35-immunophilin FK506binding protein 35, PfCBP-calcyclin-binding protein, Cns1-cyclophilin seven suppressor 1; Hop/STI1 -stress-inducible protein homolog.…”

Section: Co-chaperones Of Cytosolic Pfhsp90mentioning

confidence: 99%

Section: Plasmodial Hsp90smentioning

confidence: 99%

Inhibitors of the Plasmodium falciparum Hsp90 towards Selective Antimalarial Drug Design: The Past, Present and Future

Stofberg

Caillet

Villiers

et al. 2021

Cells

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Malaria is still one of the major killer parasitic diseases in tropical settings, posing a public health threat. The development of antimalarial drug resistance is reversing the gains made in attempts to control the disease. The parasite leads a complex life cycle that has adapted to outwit almost all known antimalarial drugs to date, including the first line of treatment, artesunate. There is a high unmet need to develop new strategies and identify novel therapeutics to reverse antimalarial drug resistance development. Among the strategies, here we focus and discuss the merits of the development of antimalarials targeting the Heat shock protein 90 (Hsp90) due to the central role it plays in protein quality control.

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Hsp90 Co-chaperones Form Plastic Genetic Networks Adapted to Client Maturation

Cited by 31 publications

References 118 publications

Human Hsp90 cochaperones: perspectives on tissue-specific expression and identification of cochaperones with similar in vivo functions

Human Hsp90 cochaperones: perspectives on tissue-specific expression and identification of cochaperones with similar in vivo functions

The functions and regulation of heat shock proteins; key orchestrators of proteostasis and the heat shock response

Inhibitors of the Plasmodium falciparum Hsp90 towards Selective Antimalarial Drug Design: The Past, Present and Future

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