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Biomolecular condensates (BMCs) are membrane-less organelles formed through liquid-liquid phase separation, primarily driven by multivalent interactions between scaffold and client molecules. These dynamic compartments enable cells to spatially and temporally organize biochemical reactions by locally concentrating specific biomolecules, thereby enhancing the frequency of productive molecular interactions and increasing reaction rates. BMCs are integral to normal cellular physiology, with well-characterized examples including the nucleolus and Cajal bodies. However, aberrant formation or regulation of condensates has been implicated in the pathogenesis of several diseases, including neurodegenerative disorders, cancer, and immune-related conditions. Intrinsically disordered regions and disease-associated mutations in key residues often promote pathological phase separation, contributing to condensate dysregulation. A comprehensive understanding of the molecular principles governing BMC biogenesis is critical for the development of novel, non-invasive therapeutic strategies aimed at modulating condensate dynamics in disease contexts.
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http://dx.doi.org/10.1016/j.jbior.2025.101105 | DOI Listing |
Nat Chem Biol
September 2025
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Many pharmaceutical targets partition into biomolecular condensates, whose microenvironments can significantly influence drug distribution. Nevertheless, it is unclear how drug design principles should adjust for these targets to optimize target engagement. To address this question, we systematically investigated how condensate microenvironments influence drug-targeting efficiency.
View Article and Find Full Text PDFMol Cell
August 2025
Lingang Laboratory, Shanghai 200031, China. Electronic address:
YAP/TAZ are transcriptional co-activators that pair with transcription factor TEA/ATTS domains (TEADs) for modulating the Hippo pathway. Previous works propose the potential role of YAP/TAZ phase separation for transcriptional activation, yet the biomolecular basis of endogenous YAP/TAZ-TEAD condensates remains unclear. Here, we dissect their endogenous morphology, revealing that YAP/TAZ are client proteins recruited to TEAD condensates in various human cell lines.
View Article and Find Full Text PDFAdv Biol Regul
September 2025
Laboratory of Cancer Cell Architecture, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address:
Biomolecular condensates (BMCs) are membrane-less organelles formed through liquid-liquid phase separation, primarily driven by multivalent interactions between scaffold and client molecules. These dynamic compartments enable cells to spatially and temporally organize biochemical reactions by locally concentrating specific biomolecules, thereby enhancing the frequency of productive molecular interactions and increasing reaction rates. BMCs are integral to normal cellular physiology, with well-characterized examples including the nucleolus and Cajal bodies.
View Article and Find Full Text PDFAnn N Y Acad Sci
September 2025
Institute of Biological and Chemical Systems, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany.
The genome stores and processes approximately 1.5 gigabytes of encoded information. In this article, we propose that the eukaryotic genome and its adaptable three-dimensional packing in the form of chromatin offer a valuable template for the system architecture of DNA-based digital computers.
View Article and Find Full Text PDFCell Rep
September 2025
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China. Electronic address:
Nuclear factor κB (NF-κB) family transcription factors are critical for innate immune responses across a variety of organisms and are frequently dysregulated in diseases. Understanding their homeostatic regulation is essential for developing therapeutic strategies. Relish, a Drosophila homolog of mammalian NF-κB precursors, provides a valuable model for studying these processes.
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