Enhancement of drug-sensitivity through the reactivation of mutant p53

我们已经确定了共伴侣人DnaJC 7作为突变型p53的结合伴侣之一。根据我们的免疫沉淀实验，在哺乳动物培养细胞中，DnaJC 7与突变型p53以及野生型p53相关。值得注意的是，DnaJC 7促进MDM 2从野生型p53解离，从而延长其半衰期并刺激其转录以及促凋亡活性。此外，荧光素酶报告基因测定证明DnaJC 7具有降低突变型p53对野生型p53的抑制作用的能力。综上所述，我们目前的研究结果强烈表明，DnaJC 7可能通过与野生型p53和/或突变型p53的物理和功能相互作用来增强恶性癌细胞的药物敏感性。

We have identified co-chaperon human DnaJC7 as one of the binding partners of mutant p53. According to our immunoprecipitation experiments, DnaJC7 was associated with mutant p53 as well as wild-type p53 in mammalian cultured cells. Of note, DnaJC7 promoted the dissociation of MDM2 from wild-type p53, and thereby extended its half-life and stimulated its transcriptional as well as pro-apoptotic activity. In addition, luciferase reporter assays demonstrated that DnaJC7 has an ability to reduce the inhibitory effect of mutant p53 on wild-type p53. Taken together, our present results strongly suggest that DnaJC7 might enhance the drug-sensitivity of malignant cancerous cells through the physical and functional interactions with wild-type p53 and/or mutant p53.