ArticleThe Journal of biological chemistry2020
Functional diversity between HSP70 paralogs caused by variable interactions with specific co-chaperones.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- Wiring of cellular proteostasis by J-domain proteins.Cell stress & chaperones · 2026Review
- Mechanisms and regulation of the Hsp70 chaperone network.Nature reviews. Molecular cell biology · 2026Review
- AKAP95 condensates regulate transcription and can be targeted in MLL-fusion driven oncogenesis.Nature communications · 2026Article
- Exogenous application of γ-aminobutyric acid alleviates temperature stress in mungbean (Vigna radiata) and its wild non-progenitor (Vigna glabrescens) by regulating heat shock protein genes.BMC plant biology · 2025Article
- TDP-43 skein-like inclusions are formed by BAG3- and HSP70-guided co-aggregation with actin-binding proteins.Nature cell biology · 2025Article
- Molecular and Biochemical Mechanisms of Cardiomyopathy Development Following Prenatal Hypoxia-Focus on the NO System.Antioxidants (Basel, Switzerland) · 2025Review
- A low-complexity linker as a driver of intra- and intermolecular interactions in DNAJB chaperones.Nature communications · 2025Article
- Co-chaperones fine-tune the function of heat shock protein 70 (Hsp70), whether to fold, hold, or degrade substrates in ensuring cellular protein homeostasis.Journal of biosciences · 2025Review
- Single-Cell RNA Sequencing Analysis of Microglia Dissected the Energy Metabolism and Revealed Potential Biomarkers in Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2024Article
- DnaK duplication and specialization in bacteria correlates with increased proteome complexity.mSystems · 2024Article
- The Physiological and Biochemical Response of Ribbed Mussels to Rising Temperatures: Benefits of Salt Marsh Cordgrass.Integrative organismal biology (Oxford, England) · 2024Article
- DnaJs are enriched in tau regulators.International journal of biological macromolecules · 2023Article
- Molecular Chaperones' Potential against Defective Proteostasis of Amyotrophic Lateral Sclerosis.Cells · 2023Review
- Analysis of damage-associated molecular patterns in amyotrophic lateral sclerosis based on ScRNA-seq and bulk RNA-seq data.Frontiers in neuroscience · 2023Article
- The APE2 Exonuclease Is a Client of the Hsp70-Hsp90 Axis in Yeast and Mammalian Cells.Biomolecules · 2022Article
- Analysis of Huntington's Disease Modifiers Using the Hyperbolic Mapping of the Protein Interaction Network.International journal of molecular sciences · 2022Article
- Large Chaperone Complexes Through the Lens of Nuclear Magnetic Resonance Spectroscopy.Annual review of biophysics · 2022Review
- The C-terminal domain of Hsp70 is responsible for paralog-specific regulation of ribonucleotide reductase.PLoS genetics · 2022Article
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Authors and funding
13 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heat shock protein 70 (HSP70) chaperones play a central role in protein quality control and are crucial for many cellular processes, including protein folding, degradation, and disaggregation. Human HSP70s compose a family of 13 members that carry out their functions with the aid of even larger families of co-chaperones. A delicate interplay between HSP70s and co-chaperone recruitment is thought to determine substrate fate, yet it has been generally assumed that all Hsp70 paralogs have similar activities and are largely functionally redundant. However, here we found that when expressed in human cells, two highly homologous HSP70s, HSPA1A and HSPA1L, have opposing effects on cellular handling of various substrates. For example, HSPA1A reduced aggregation of the amyotrophic lateral sclerosis-associated protein variant superoxide dismutase 1 (SOD1)-A4V, whereas HSPA1L enhanced its aggregation. Intriguingly, variations in the substrate-binding domain of these HSP70s did not play a role in this difference. Instead, we observed that substrate fate is determined by differential interactions of the HSP70s with co-chaperones. Whereas most co-chaperones bound equally well to these two HSP70s, Hsp70/Hsp90-organizing protein (HOP) preferentially bound to HSPA1L, and the Hsp110 nucleotide-exchange factor HSPH2 preferred HSPA1A. The role of HSPH2 was especially crucial for the HSPA1A-mediated reduction in SOD1-A4V aggregation. These findings reveal a remarkable functional diversity at the level of the cellular HSP70s and indicate that this diversity is defined by their affinities for specific co-chaperones such as HSPH2.
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Registered trials
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