Identification And Biological Function Of Acetylation Modifying Cofactor In

The post-transcriptional modifications of p53is the main way to perform its function of transcription factor and tumor suppressor. Recent reports indicated that MYST proteins:Tip60and hMOF can acetylate p53at Lysine120in response to DNA damage.Different modification status of this specific site activated different target genes in p53pathway and subsequently decided cell fate. Although the acetylation of p53K120is critical to tumorigenesis, the precise mechanism is still unclear.In this study, ING5was found to be involved in the acetylation of p53K120by Tip60. Force expression of ING5can increase the level of acetylated p53. In contrast, after knock down ING5by shRNA, we observed that p53K120can’t be acetylated anymore, but the acetylation of p53other lysines were not affected. This result strongly suggests that ING5is involved in the process of p53K120acetylation. The results of protein-protein interaction and siRNA confirm our presumption. ING5affects acetylation of p53K120by Tip60, not hMOF. These results exibit the site-specific character of ING5.Acetyl-K120p53can activate apoptosis-related gene. We found that the expression level of ING5can affect transcription activity of apoptosis-related gene in both p53-wild type cell line and p53-null cell line. ChIP assay prove that ING5can be recruited to the promoter region of apoptosis-related gene as well as acetyl-K120p53and Tip60, and the acetylation level of histone H4in these region increase.During our study, we found that ING5can be activated in response to DNA damage caused by anti-tumor drugs. The results of Western-Blot, real-time PCR and ICC showed that ING5can be activated in response to DNA damage and accumulates in nuclear in dose-dependent manner. And ING5accumualtes in nuclear druing mitosis process. We need further study to explain the precise mechanism.In this study, we proved that ING5can be activated in response to drug-dependent DNA damage and subsequently work with Tip60in acetylation of p53K120. It can also be recruited to the promoter region of apoptosis-related gene and induce apoptosis.