Professor Special Lecture: 154th Regular Meeting of the Medical Society of Toho University: Multifunctional Protein DJ-1 and Disease - 20 Years since the Isolation of the DJ-1 Gene, and Future Research -

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type:TOHO University Scholarly Publication

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We have researched the initiation of DNA replication for many years, and as part of that research, we have performed functional analysis of the oncogene product c-Myc. Therefore, yeast two-hybrid screening was used to search for protein candidates that bind to the c-Myc protein and control its function. DJ-1 was originally isolated as a c-Myc-binding protein. However, subsequent furthered studies revealed that it did not bind to c-Myc. At that time, we were routinely performing focus formation analysis. Focus formation analysis was conducted to analyze focus formation efficiency by introducing various genes into mouse NIH3T3 fibroblasts or mouse embryonic fibroblasts in order to examine whether these genes promote carcinogenesis. The DJ-1 gene was used as a negative control. As a result of the experiment, we found that DJ-1 cooperates with ras to promote transformation of cells. In 1997, DJ-1 was reported by us as being a novel oncogene that promotes cell carcinogenesis with ras cooperatively. DJ-1 was named after two students, Daisuke and Junko, who were researching this gene with me. Furthermore, we have reported the following functions. 1,Significantly increased proteins in testis exposed endocrine disruptors. 2,Positive transcription regulator of androgen receptor. 3,Essential for fertilization. In 2003, Bonifati et al. reported that DJ-1 (PARK7) is a causative gene for familial Parkinson's disease. Thus, it became clear that DJ-1 is a multifunctional protein with various biological functions. Here, I introduce the findings we have clarified over the past to present of the function of DJ-1 as an oxidative stress defense factor and another functions. Furthermore, I will introduce the new features of DJ-1 that have been reported in recent years, and introduce possible clinical diagnostic index and the therapeutic drug development based on the DJ-1 protein.

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