53BP1蛋白对P53转录调控活性的影响

Protein 53BP1 regulates the transcription activity of P53

目的 :探索含有BRCT结构域的P5 3分子结合蛋白 5 3BP1调控P5 3转录活性的机制。方法 :通过PCR的方法获得缺失不同结构域的 5 3BP1基因突变体 5 3BP1Δ1,5 3BP1Δ2 ,5 3BP1Δ3与 5 3BP1Δ4 ,并采用双荧光素酶报告基因系统分析了它们对P5 3蛋白转录活性的影响。结果与结论 :野生型 5 3BP1蛋白可以明显提高P5 3的转录活性 ,其C端的BRCT结构域与核定位信号的存在为必不可少 ,而N端与P2 0 2蛋白相互结合结构域的存在也可以促进P5 3的转录活性 ,提示 5 3BP1蛋白不同功能结构域之间的协同作用是保证其行使正常生理功能的前提条件。

Ojective: To reveal the mechanism of 53BP1(P53 binding protein 1),which contains a BRCT domain, in regulating the transcriptional activity of P53. Methods: To identify the region of 53BP1 required for enhancing the transcriptional activity of P53, four 53BP1 deletion constructs (53BP1Δ1, 53BP1Δ2, 53BP1Δ3 and 53BP1Δ4) were generated by PCR and their effects on P53 transcription were analysed in SoaS-2 cells by dual-luciferase reporter assay system. Results and Conclusions: Wild type 53BP1 enhanced the transcriptional activity of P53 significantly. The C terminal of 53BP1 protein containing BRCT domain and nuclear localization signal was required for its transcriptional enhancing activity and the N terminal domain of 53BP1 which interacted with P202 protein also contributed to its transcriptional enhancing activity, suggesting that the cooperation of the different domains of 53BP1 protein is required for its normal function.