目的·探索SENP3介导的去SUMO化修饰（de-SUMO修饰）对p53的定位和活性的影响。方法·选取肺癌细胞系A549（p53野生型）和H1299（p53缺失型）分别作为内源表达p53和强制表达p53的细胞模型；野生型及SUMO修饰位点突变型p53转染细胞,比较SUMO化修饰的效应。免疫共沉淀技术检测静息或氧化应激时p53的SUMO2/3修饰及SENP3的去除作用；免疫荧光技术检测上述修饰及SENP3的调控对p53定位的影响；双荧光素酶报告基因和定量实时PCR方法检测p53促进p21转录的活性；生长曲线检测细胞增殖，探讨上述修饰和调控的生物学效应。结果· SENP3可介导p53的de-SUMO2/3修饰，且氧化应激时更为明显。p53的de-SUMO2/3修饰不影响p53定位，但抑制其促转录活性，并且取消其增殖抑制功能。结论·人肺癌细胞系中SENP3介导p53的de-SUMO2/3修饰可能是p53失活的机制之一。

Objective · To explore the effect of de-SUMOylation of p53SENP3 on its transcriptional activity in lung cancer. Methods · Lung cancer cell lines A549 (p53 wild type) and H1299 (p53 ) were used. Wild type p53 as well as sumoless mutants K386R or E388A were introduced into the cells. Co-immunoprecipitation was performed to detect SUMOylation of p53 under resting status or oxidative stress. Immunofluorescence was applied to observe the localization of p53 WT and K386R or E388A. Dual luciferase reporter assay and quantitative real-time PCR of p21 were performed to monitor the transcriptional activity of p53 WT and K386R or E388A. Growth curve was analyzed to demonstrate the effect of p53 WT and K386R or E388A on cell proliferation. Results · SENP3 was able to mediate de-SUMOylation modification of p53 under oxidative stress. Similar to WT p53, K386R and E388A p53 kept nuclear localization. Further, SENP3 knockdown or oxidative stress did not induce translocation of p53 nucleus to cytoplasm. However, compared to WT, the transcriptional activation of K386R and E388A p53 were inhibited. Moreover, SENP3 inhibited the activity of p53 in A549. K386R and E388A p53 attenuated the inhibitive activity on cell proliferation in H1299. Conclusion · SENP3-mediated de-SUMOylation of p53 is one of mechanisms of its inactivation as tumor suppressor in lung cancer.