Department of Bioscience, Changchun Normal University, 677 Changji Northroad, Changchun 130032, Jilin, China.
J Biosci. 2020;45.
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.
作为一种肿瘤抑制因子，p53 可在真核生物中维持基因组完整性。然而，关于 p53 在细胞质和细胞核之间穿梭的证据有限。先前的研究表明，β-肌动蛋白聚合通过与 p53 相互作用负调控 p53 的核输入。在这项研究中，我们发现 DNA 损伤诱导β-肌动蛋白和 p53 在核内积累。β-肌动蛋白敲低会损害 p53 的核转运。此外，β-肌动蛋白可以与 p53 相互作用，而 p53 在受到遗传毒性应激时会增强这种相互作用。此外，p53 的 N 端缺失突变体显示与β-肌动蛋白的关联水平降低。我们进一步鉴定出 p53 的 Ser15、Thr18 和 Ser20 对β-肌动蛋白：p53 相互作用至关重要，这些氨基酸突变为丙氨酸会破坏结合。总之，这项研究揭示了β-肌动蛋白通过蛋白-蛋白相互作用调节 p53 的核输入。
