β-Actin facilitates etoposide-induced p53 nuclear import

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 beta -actin polymerization negatively regulates p53 nuclear import through its interaction with p53. In this study, we found that DNA damage induces both beta -actin and p53 accumulation in the nucleus. beta -actin knockdown impaired the nuclear transport of p53. Additionally, beta -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 beta -actin. We further identified Ser15, Thr18 and Ser20 of p53 are critical to the beta -actin: p53 interaction, which upon mutation into alanine abrogates the binding. Taken together, this study reveals that beta -actin regulates the nuclear import of p53 through protein-protein interaction.