ArticleMolecular biology and evolution2015
Hsp90 promotes kinase evolution.
Article in Molecular biology and evolution, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
- Review
- Identification of thePlants (Basel, Switzerland) · 2025Article
- Genome-wide identification and characterization ofFrontiers in plant science · 2025Article
- The Hsp90 Molecular Chaperone as a Global Modifier of the Genotype-Phenotype-Fitness Map: An Evolutionary Perspective.Journal of molecular biology · 2024Review
- Discovery of new Hsp90-Cdc37 protein-protein interaction inhibitors:RSC advances · 2024Article
- Tracing genetic diversity captures the molecular basis of misfolding disease.Nature communications · 2024Article
- Review
- Viruses and amyloids - a vicious liaison.Prion · 2023Review
- Insights and Perspectives on the Role of Proteostasis and Heat Shock Proteins in Fungal Infections.Microorganisms · 2023Review
- Article
- MaizePeerJ · 2023Article
- DnaK response to expression of protein mutants is dependent on translation rate and stability.Communications biology · 2022Article
- Differential maturation and chaperone dependence of the paralogous protein kinases DYRK1A and DYRK1B.Scientific reports · 2022Article
- Thermal stress and mutation accumulation increase heat shock protein expression inEvolutionary ecology · 2022Article
- Genome-Wide Study ofFrontiers in plant science · 2022Article
- Molecular Chaperones Accelerate the Evolution of Their Protein Clients in Yeast.Genome biology and evolution · 2019Article
- It's not magic - Hsp90 and its effects on genetic and epigenetic variation.Seminars in cell & developmental biology · 2019Review
- Decanalizing thinking on genetic canalization.Seminars in cell & developmental biology · 2019Review
- Genome-wide identification and expression analysis of HSP90 gene family in Nicotiana tabacum.BMC genetics · 2019Article
- Identification and Therapeutic Intervention of Coactivated Anaplastic Lymphoma Kinase, Fibroblast Growth Factor Receptor 2, and Ephrin Type-A Receptor 5 Kinases in Hepatocellular Carcinoma.Hepatology (Baltimore, Md.) · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Heat-shock protein 90 (Hsp90) promotes the maturation and stability of its client proteins, including many kinases. In doing so, Hsp90 may allow its clients to accumulate mutations as previously proposed by the capacitor hypothesis. If true, Hsp90 clients should show increased evolutionary rate compared with nonclients; however, other factors, such as gene expression and protein connectivity, may confound or obscure the chaperone's putative contribution. Here, we compared the evolutionary rates of many Hsp90 clients and nonclients in the human protein kinase superfamily. We show that Hsp90 client status promotes evolutionary rate independently of, but in a small magnitude similar to that of gene expression and protein connectivity. Hsp90's effect on kinase evolutionary rate was detected across mammals, specifically relaxing purifying selection. Hsp90 clients also showed increased nucleotide diversity and harbored more damaging variation than nonclient kinases across humans. These results are consistent with the central argument of the capacitor hypothesis that interaction with the chaperone allows its clients to harbor genetic variation. Hsp90 client status is thought to be highly dynamic with as few as one amino acid change rendering a protein dependent on the chaperone. Contrary to this expectation, we found that across protein kinase phylogeny Hsp90 client status tends to be gained, maintained, and shared among closely related kinases. We also infer that the ancestral protein kinase was not an Hsp90 client. Taken together, our results suggest that Hsp90 played an important role in shaping the kinase superfamily.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.