Liquid-like droplet formation by tumor suppressor p53 induced by multivalent electrostatic interactions between two disordered domains

Kiyoto Kamagata, Saori Kanbayashi, Masaya Honda, Yuji Itoh, Hiroto Takahashi, Tomoshi Kameda, Fumi Nagatsugi, Satoshi Takahashi

研究成果: Article査読

11 被引用数 (Scopus)

抄録

Early in vivo studies demonstrated the involvement of a tumor-suppressing transcription factor, p53, into cellular droplets such as Cajal and promyelocytic leukemia protein bodies, suggesting that the liquid-liquid phase separation (LLPS) might be involved in the cellular functions of p53. To examine this possibility, we conducted extensive investigations on the droplet formation of p53 in vitro. First, p53 itself was found to form liquid-like droplets at neutral and slightly acidic pH and at low salt concentrations. Truncated p53 mutants modulated droplet formation, suggesting the importance of multivalent electrostatic interactions among the N-terminal and C-terminal domains. Second, FRET efficiency measurements for the dimer mutants of p53 revealed that distances between the core domains and between the C-terminal domains were modulated in an opposite manner within the droplets. Third, the molecular crowding agents were found to promote droplet formation, whereas ssDNA, dsDNA, and ATP, to suppress it. Finally, the p53 mutant mimicking posttranslational phosphorylation did not form the droplets. We conclude that p53 itself has a potential to form droplets that can be controlled by cellular molecules and by posttranslational modifications, suggesting that LLPS might be involved in p53 function.

本文言語English
論文番号580
ジャーナルScientific reports
10
1
DOI
出版ステータスPublished - 2020 12 1

ASJC Scopus subject areas

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