Actin Involves In The Regulation Of P53Stability Through Recruiting The Aurora Kinase A

During DNA damage response, the tumor suppressor protein P53is one of the key regulatory molecules. Under non-stress conditions P53is continuously generated accompanying ubiquitination degradation with low P53stability. DNA damage induce P53phosphorylation on serine/threonine residues enhancing P53stability. Therefore, the enhancement of P53stability and nucleo-cytoplasmic localization of P53play an important role in tumor suppression.Actin exists in monomer (G-actin) and polymeric (F-actin) forms. Studies show that there is interaction between F-actin and P53. In response to DNA damage, F-actin and P53combine more closely. In addition, actin can bind to the ATP enzyme subunit Brgl of BAF chromatin remodeling complex, participating in gene transcriptionl regulation. Aurora A can regulate P53stability and its transcriptional activity through direct phosphorylation of P53. P53inhibit the function of Aurora A through combining to Aurora A catalytic domain.To study the relationship between actin, Aurora A and P53in response to DNA damage, we use human osteosarcoma U2OS cell lines as the main experimental materials and establish a chemotherapy drug etoposide inducing DNA damage model. We find that overexpression of actin reduces P53stability through promoting the degradation of P53. Further experiments prove that actin reduce P53stability by promoting Ser315sites phosphorylation of P53. We prove that interfering the expression of Aurora A up-regulates P53expression level as well as down-regulates Ser315sites phosphorylation of P53. Furtherly, we identified that actin and Aurora A are present in the same complexes through immunoprecipitation in vivo. We also identify that Actin(particularly F-actin) involves in the regulation of P53stability through recruiting the Aurora kinase A.