ArticleProceedings of the National Academy of Sciences of the United States of America2020
Hsp40 proteins phase separate to chaperone the assembly and maintenance of membraneless organelles.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- A comparative meta-analysis of membraneless organelle-associated proteins with age related proteome of C. elegans.Cell stress & chaperones · 2022Pooled it
- FBXL21 regulates diurnal proteostasis in skeletal muscle by targeting DNAJB6 and client proteins.EMBO reports · 2026Article
- An ALS-associated mutation in the C-terminal α-helix of TDP-43 uncouples condensate formation and amyloid assembly.Protein science : a publication of the Protein Society · 2026Article
- Anhydrobiosis as a Model of Aging and Longevity: The Role of Autophagy and Metabolism in Yeast Cells.Microbial ecology · 2026Review
- Omega stabilizes RNA polymerase condensates and contributes to cellular fitness during acid stress.bioRxiv : the preprint server for biology · 2026Article
- Review
- Decoupling phase separation and fibrillization preserves activity of biomolecular condensates.Nature communications · 2026Article
- Dynamic regulation of endogenous transcription factor hubs at single-molecule resolution.bioRxiv : the preprint server for biology · 2026Article
- Physiological and pathological roles of ANXA11: a multifunctional regulator in neurodegeneration and other disorders.Cell communication and signaling : CCS · 2026Review
- Condensatopathies as a mechanistic framework for disease and integrated theranostic intervention.Theranostics · 2026Review
- Multiplex neurodegeneration proteotoxicity platform reveals DNAJB6 promotes non-toxic FUS condensate gelation and inhibits neurotoxicity.Nature communications · 2025Article
- Mechanisms of assembly and function of the Hsp70-Hsp40 chaperone machinery.Molecular cell · 2025Article
- Zinc finger domains bind low-complexity domain polymers.Nature communications · 2025Article
- Mechanisms and Pathological Significance of Liquid-Liquid Phase Separation in Bacteria.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- A multichaperone condensate enhances protein folding in the endoplasmic reticulum.Nature cell biology · 2025Article
- Organization of the Proteostasis Network of Membraneless Organelles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities.Molecular cancer · 2025Review
- Rational Modulation of Liquid-Liquid Phase Separation Offers Novel Ways to Combat Tauopathies.International journal of molecular sciences · 2025Review
- Regulation of physiological and pathological condensates by molecular chaperones.The FEBS journal · 2025Review
- DNAJC12 downregulation induces neuroblastoma progression via increased histone H4K5 lactylation.Journal of molecular cell biology · 2025Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Membraneless organelles contain a wide spectrum of molecular chaperones, indicating their important roles in modulating the metastable conformation and biological function of membraneless organelles. Here we report that class I and II Hsp40 (DNAJ) proteins possess a high ability of phase separation rendered by the flexible G/F-rich region. Different Hsp40 proteins localize in different membraneless organelles. Specifically, human Hdj1 (DNAJB1), a class II Hsp40 protein, condenses in ubiquitin (Ub)-rich nuclear bodies, while Hdj2 (DNAJA1), a class I Hsp40 protein, condenses in nucleoli. Upon stress, both Hsp40 proteins incorporate into stress granules (SGs). Mutations of the G/F-rich region not only markedly impaired Hdj1 phase separation and SG involvement and disrupted the synergistic phase separation and colocalization of Hdj1 and fused in sarcoma (FUS) in cells. Being cophase separated with FUS, Hdj1 stabilized the liquid phase of FUS against proceeding into amyloid aggregation in vitro and alleviated abnormal FUS aggregation in cells. Moreover, Hdj1 uses different domains to chaperone FUS phase separation and amyloid aggregation. This paper suggests that phase separation is an intrinsic property of Hsp40 proteins, which enables efficient incorporation and function of Hsp40 in membraneless organelles and may further mediate the buildup of chaperone network in membraneless organelles.
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