title: Actin polymerization negatively regulates p53 function by impairing its nuclear import in response to DNA damage.
abstract: Actin, one of the most evolutionarily conservative proteins in eukaryotes, is distributed both in the cytoplasm and the nucleus, and its dynamics plays important roles in numerous cellular processes. Previous evidence has shown that actin interacts with p53 and this interaction increases in the process of p53 responding to DNA damage, but the physiological significance of their interaction remains elusive. Here, we show that DNA damage induces both actin polymerization and p53 accumulation. To further understand the implication of actin polymerization in p53 function, cells were treated with actin aggregation agent. We find that the protein level of p53 decrease. The change in p53 is a consequence of the polymeric actin anchoring p53 in the cytoplasm, thus impairing p53 nuclear import. Analysis of phosphorylation and ubiquitination of p53 reveals that actin polymerization promotes the p53 phosphorylation at Ser315 and reduces the stabilization of p53 by recruiting Aurora kinase A. Taken together, our results suggest that the actin polymerization serves as a negative modulator leading to the impairment of nuclear import and destabilization of p53. On the basis of our results, we propose that actin polymerization might be a factor participating in the process of orchestrating p53 function in response to DNA damage.
authors.affiliation: Key Laboratory of Molecular Epigenetics of MOE and the Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Shuyan
authors.initials: S
authors.lastname: Wang
authors.forename: Tianyang
authors.initials: T
authors.lastname: Qi
authors.forename: Lijing
authors.initials: L
authors.lastname: Guo
authors.forename: Jinjiao
authors.initials: J
authors.lastname: Li
authors.forename: Wenjing
authors.initials: W
authors.lastname: Qi
authors.forename: Khamal Kwesi
authors.initials: KK
authors.lastname: Ampah
authors.forename: Xueqing
authors.initials: X
authors.lastname: Ba
authors.forename: Xianlu
authors.initials: X
authors.lastname: Zeng
mesh_terms: D000199:Actins / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D055503:Protein Multimerization; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D000199:Actins; D016159:Tumor Suppressor Protein p53; D015689:Oncogene Protein p21(ras)
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