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.
Highlights
DNA damage contributes to the development of many human cancers [1]
Actin interacts with p53, and the interaction is enhanced when DNA damage happens [23], but the elaborate dynamics of actin respond to DNA damage and its physiological significance remain elusive
To explore the dynamic changes of actin upon DNA damage, we first examined the morphology of cells treated with etoposide (ETO), a genetoxic agent that enhances the cleavage of DNA double-strand [30]
Summary
DNA damage contributes to the development of many human cancers [1]. Cells respond to DNA damage by inhibiting DNA synthesis, allowing them to avoid progressive increases in genomic changes and neoplastic transformation [2,3]. p53 plays an important role in the inhibition of DNA synthesis by activating cell cycle arrest related genes [4,5,6,7]. In response to DNA damage, p53 rapidly accumulates in the nucleus, where it functions as a transcriptional factor to modulate the expression of cell-cycle- and/or apoptosis -related genes [9]. Mot (mortalin 2), an hsp (the 70 kilodalton heat shock proteins) family member, interacts with p53 and inhibits its nuclear import [16]. These proteins regulate p53 cellular localization positively or negatively, and orchestrate the choice of p53 between different subsets of cell cycle arrest genes or apoptosis genes in response to various level of DNA damage [17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
