摘要
鼠双微体基因X(MdmX)是肿瘤抑制因子p53信号通路中重要的负调控蛋白,它能与p53直接结合,抑制p53的转录活性.体轴发育抑制因子Axin作为构架蛋白与p53及同源结构域互作蛋白激酶2(HIPK2)等相互作用形成复合物,诱导p53的转录活化,共同促进细胞的凋亡.本研究将MdmX引入Axin-p53信号通路的调控中,发现MdmX通过竞争Axin与p53的结合,抑制Axin诱导p53的转录激活.p53结合区域缺失的MdmX突变体MdmXΔp53则不能抑制Axin对p53的激活.这些实验结果为进一步深入研究Axin-p53信号通路在细胞凋亡及肿瘤发生发展中的作用提供了重要的理论依据.
Mouse double minute X(MdmX)is a key negative regulator of the tumor suppressor p53.It directly interacts with p53, and inhibits the transcriptional activity of p53.Axin(Axis inhibitor)is an essential scaffold protein participating in many signaling pathways including Wnt signaling,the JNK MAP kinase cascade,TGF-βsignaling as well as p53signaling.It forms a p53activating complex to induce the apoptosis-related p53transcriptional activation.To evaluate the function of MdmX in Axin-p53signaling pathway,p53-luciferase reporter gene assay and Co-immunoprecipitation experiments were conducted.Here,we show that MdmX can inhibit Axin-induced p53transcriptional activation by competing the interaction of p53with Axin.MdmXΔp53,a MdmX deletion mutant that lacks p53binding domain,fails to exert the inhibitory effect.These results provide the foundation for further study on the role of Axin-p53signaling pathway in cell apoptosis and tumorigenesis.
出处
《厦门大学学报（自然科学版）》
CAS
CSCD
北大核心
2014年第1期110-114,共5页
Journal of Xiamen University：Natural Science
基金
国家自然科学基金(31101014)
