ArticleEMBO reports2022
Mechanistic insights into enhancement or inhibition of phase separation by different polyubiquitin chains.
Article in EMBO reports, 2022. 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, 53 citations in OpenAlex.
- Microfluidics for protein interaction studies: current methods, challenges, and future perspectives.European biophysics journal : EBJ · 2026Review
- Review
- Dual regulation of metabolic reprogramming and protein competitive modifications: the core role and mechanism of MRPL36 in glioblastoma malignant progression.Journal of experimental & clinical cancer research : CR · 2026Article
- Conformational landscapes resolved by ion mobility mass spectrometry reveal mechanisms of polyubiquitin-controlled phase separation.Chemical science · 2026Article
- Molecular architecture of meiotic pro-crossover factor HEI10 reveals coupling of higher-order assembly and ubiquitin chain formation.bioRxiv : the preprint server for biology · 2026Article
- STI1 domains coordinate partitioning of UBQLN2 into stress-induced condensates.bioRxiv : the preprint server for biology · 2026Article
- ALS mutations disrupt self-association between the ubiquilin STI1 hydrophobic groove and internal placeholder sequences.The EMBO journal · 2026Article
- STI1 domain engages transient helices to mediate Dsk2 phase separation and proteasome condensation.The EMBO journal · 2026Article
- TBK1 Induces the Formation of Optineurin Filaments That Condensate with Polyubiquitin and LC3 for Cargo Sequestration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ubiquitin-Mediated Proteolysis as a Regulator of the Plant Defense-Growth Balance.Plants (Basel, Switzerland) · 2026Review
- The secreted staphylococcal biofilm protein Sbp forms biomolecular condensates in the presence of DNA.Protein science : a publication of the Protein Society · 2026Article
- Biomolecular Phase Boundaries are Described by a Solubility Product That Accounts for Variable Stoichiometry and Soluble Oligomers.Journal of the American Chemical Society · 2025Article
- Ubiquilin-2 liquid droplets catalyze α-synuclein fibril formation.The EMBO journal · 2025Article
- Biomolecular phase boundaries are described by a solubility product that accounts for variable stoichiometry and soluble oligomers.bioRxiv : the preprint server for biology · 2025Article
- Phase Separation Clustering of Poly Ubiquitin Cargos on Ternary Mixture Lipid Membranes by Synthetically Cross-Linked Ubiquitin Binder Peptides.Biochemistry · 2025Article
- Protein quality control machinery: regulators of condensate architecture and functionality.Trends in biochemical sciences · 2025Review
- Article
- Phase separation of polyubiquitinated proteins in UBQLN2 condensates controls substrate fate.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Phase separation of polyubiquitinated proteins in UBQLN2 condensates controls substrate fate.bioRxiv : the preprint server for biology · 2024Article
- Proteasome condensate formation is driven by multivalent interactions with shuttle factors and ubiquitin chains.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Ubiquitin-binding shuttle UBQLN2 mediates crosstalk between proteasomal degradation and autophagy, likely via interactions with K48- and K63-linked polyubiquitin chains, respectively. UBQLN2 comprises self-associating regions that drive its homotypic liquid-liquid phase separation (LLPS). Specific interactions between one of these regions and ubiquitin inhibit UBQLN2 LLPS. Here, we show that, unlike ubiquitin, the effects of multivalent polyubiquitin chains on UBQLN2 LLPS are highly dependent on chain types. Specifically, K11-Ub4 and K48-Ub4 chains generally inhibit UBQLN2 LLPS, whereas K63-Ub4, M1-Ub4 chains, and a designed tetrameric ubiquitin construct significantly enhance LLPS. We demonstrate that these opposing effects stem from differences in chain conformations but not in affinities between chains and UBQLN2. Chains with extended conformations and increased accessibility to the ubiquitin-binding surface promote UBQLN2 LLPS by enabling a switch between homotypic to partially heterotypic LLPS that is driven by both UBQLN2 self-interactions and interactions between multiple UBQLN2 units with each polyubiquitin chain. Our study provides mechanistic insights into how the structural and conformational properties of polyubiquitin chains contribute to heterotypic LLPS with ubiquitin-binding shuttles and adaptors.
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Registered trials
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.