دورية أكاديمية
Identification of Small Molecules that Modulate Mutant p53 Condensation.
| العنوان: | Identification of Small Molecules that Modulate Mutant p53 Condensation. |
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| المؤلفون: | Lemos C; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Schulze L; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Weiske J; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Meyer H; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Braeuer N; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Barak N; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Eberspächer U; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Werbeck N; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Stresemann C; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Lange M; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Lesche R; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Zablowsky N; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Juenemann K; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Kamburov A; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Luh LM; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Leissing TM; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Mortier J; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Steckel M; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Steuber H; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Eis K; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Eheim A; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany., Steigemann P; Bayer AG Research and Development, Pharmaceuticals, Müllerstr. 178, 13342 Berlin, Germany. |
| المصدر: | IScience [iScience] 2020 Sep 01; Vol. 23 (9), pp. 101517. Date of Electronic Publication: 2020 Sep 01 (Print Publication: 2020). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101724038 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-0042 (Electronic) Linking ISSN: 25890042 NLM ISO Abbreviation: iScience Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, [2018]- |
| مستخلص: | Structural mutants of p53 induce global p53 protein destabilization and misfolding, followed by p53 protein aggregation. First evidence indicates that p53 can be part of protein condensates and that p53 aggregation potentially transitions through a condensate-like state. We show condensate-like states of fluorescently labeled structural mutant p53 in the nucleus of living cancer cells. We furthermore identified small molecule compounds that interact with the p53 protein and lead to dissolution of p53 structural mutant condensates. The same compounds lead to condensation of a fluorescently tagged p53 DNA-binding mutant, indicating that the identified compounds differentially alter p53 condensation behavior depending on the type of p53 mutation. In contrast to p53 aggregation inhibitors, these compounds are active on p53 condensates and do not lead to mutant p53 reactivation. Taken together our study provides evidence for structural mutant p53 condensation in living cells and tools to modulate this process. Competing Interests: All authors are or were employees of Bayer AG. (© 2020 The Author(s).) |
| فهرسة مساهمة: | Keywords: Biochemistry Methods; Medical Biochemistry; Structural Biology |
| تواريخ الأحداث: | Date Created: 20200914 Latest Revision: 20230816 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC7495113 |
| DOI: | 10.1016/j.isci.2020.101517 |
| PMID: | 32927263 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2589-0042 |
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| DOI: | 10.1016/j.isci.2020.101517 |