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. 2023 Mar 1:230:123221.
doi: 10.1016/j.ijbiomac.2023.123221. Epub 2023 Jan 10.

Phosphorylation and specific DNA improved the incorporation ability of p53 into functional condensates

Qunyang Chen  1 , Yiping Wu  1 , Zhuojun Dai  1 , Zhuqing Zhang  2 , Xiaorong Yang  3
Affiliations

Phosphorylation and specific DNA improved the incorporation ability of p53 into functional condensates

Qunyang Chen et al. Int J Biol Macromol. .

Abstract

The transcription factor p53 acted as a critical tumor suppressor by activating the expression of various target genes to regulate diverse cellular responses. The phosphorylation of p53 influenced the binding of p53 to promotor-specific DNA and the choice of cell fate. In this study, we found that full-length wild-type p53 and pol II CTD could form heterotypic phase separation condensates in vitro. The heterotypic condensates of p53 and pol II CTD were mediated by electrostatic and hydrophobic interactions between pol II CTD and multiple domains of p53. The mobility of heterotypic p53 and pol II CTD droplets was significantly higher than that of p53 droplet. The phosphorylation promoted p53 to be recruited into pol II CTD droplets and transcription condensates. The specific DNA could further enhance the incorporation ability of p53 into functional condensates. Therefore, we proposed that the p53 droplet might be in a mediate state, the mutations resulting in p53 mutants with gain-of-function impelled the aggregate of p53, while the phosphorylation promoted p53 to be recruited into functional condensates as a client molecule to exert its function. This study might provide insights into the regulation mechanism that the phosphorylation and nuclei acid affected the phase behavior of p53.

Keywords: Phase separation; Pol II CTD; p53.

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Conflict of interest statement

Declaration of competing interest The authors declare that there are no competing interests associated with the manuscript.

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