Enhancement of drug-sensitivity through the reactivation of mutant p53

点击翻译按钮获取中文摘要

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.