Anomalous Dense Liquid Condensates Host the Nucleation of Tumor Suppressor p53 Fibrils

Simple item page
dc.citation.firstpage342en_US
dc.citation.journalTitleiScienceen_US
dc.citation.lastpage355en_US
dc.citation.volumeNumber12en_US
dc.contributor.authorSafari, Mohammad S.en_US
dc.contributor.authorWang, Zhiqingen_US
dc.contributor.authorTailor, Kunaalen_US
dc.contributor.authorKolomeisky, Anatoly B.en_US
dc.contributor.authorConrad, Jacinta C.en_US
dc.contributor.authorVekilov, Peter G.en_US
dc.date.accessioned2019-12-05T18:52:32Zen_US
dc.date.available2019-12-05T18:52:32Zen_US
dc.date.issued2019en_US
dc.description.abstractAbout half of human cancers are associated with mutations of the tumor suppressor p53. Gained oncogenic functions of the mutants have been related to aggregation behaviors of wild-type and mutant p53. The thermodynamic and kinetic mechanisms of p53 aggregation are poorly understood. Here we find that wild-type p53 forms an anomalous liquid phase. The liquid condensates exhibit several behaviors beyond the scope of classical phase transition theories: their size, ca. 100 nm, is independent of the p53 concentration and decoupled from the protein mass held in the liquid phase. Furthermore, the liquid phase lacks constant solubility. The nucleation of p53 fibrils deviates from the accepted mechanism of sequential association of single solute molecules. We find that the liquid condensates serve as pre-assembled precursors of high p53 concentration that facilitate fibril assembly. Fibril nucleation hosted by precursors represents a novel biological pathway, which opens avenues to suppress protein fibrillation in aggregation diseases.en_US
dc.identifier.citationSafari, Mohammad S., Wang, Zhiqing, Tailor, Kunaal, et al.. "Anomalous Dense Liquid Condensates Host the Nucleation of Tumor Suppressor p53 Fibrils." <i>iScience,</i> 12, (2019) Cell Press: 342-355. https://doi.org/10.1016/j.isci.2019.01.027.en_US
dc.identifier.digitalAnomalous-Dense-Liquiden_US
dc.identifier.doihttps://doi.org/10.1016/j.isci.2019.01.027en_US
dc.identifier.urihttps://hdl.handle.net/1911/107771en_US
dc.language.isoengen_US
dc.publisherCell Pressen_US
dc.rightsThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.titleAnomalous Dense Liquid Condensates Host the Nucleation of Tumor Suppressor p53 Fibrilsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Anomalous-Dense-Liquid.pdf
Size:
4.88 MB
Format:
Adobe Portable Document Format
Download
Collections
Faculty Publications
Chemistry Publications