As a tumor suppressor, p53 preserves genomic integrity in eukaryotes. However, limited evidence is available for the p53 shuttling between the cytoplasm and nucleus. Previous studies have shown that β-actin polymerization negatively regulates p53 nuclear import through its interaction with p53. In this study, we found that DNA damage induces both β-actin and p53 accumulation in the nucleus. β-actin knockdown impaired the nuclear transport of p53. Additionally, β-actin could interact with p53 which was enhanced in response to genotoxic stress. Furthermore, N terminal deletion mutants of p53 shows reduced levels of association with β-actin. We further identified Ser15, Thr18 and Ser20 of p53 are critical to the β-actin: p53 interaction, which upon mutation into alanine abrogates the binding. Taken together, this study reveals that β-actin regulates the nuclear import of p53 through protein–protein interaction.
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phosphorylated histone H2AX
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This work was supported by the Natural Science Foundation of the Jilin Province Department of Science and Technology under Grant Number 20180520104JH; National Nature Science Foundation of China under Grant Number 31801182; and Natural Science Foundation of Changchun Normal University under Grant Numbers 2015-001 and 2016-001.
Corresponding editor: Kundan Sengupta
Communicated by Kundan Sengupta.
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Qi, W., Li, J., Pei, X. et al. β-Actin facilitates etoposide-induced p53 nuclear import. J Biosci 45, 34 (2020). https://doi.org/10.1007/s12038-020-0004-2
- DNA damage
- nuclear localization