Expression and protease activity of mouse legumain are regulated by the oncogene/transcription co-activator, DJ-1 through p53 and cleavage of annexin A2 is increased in DJ-1-knockout cells

Legumain (EC 3.4.22.34) is an asparaginyl endopeptidase. Strong legumain activity was observed in the mouse kidney, and legumain was highly expressed in tumors. We previously reported that bovine kidney annexin A2 was co-purified with legumain and that legumain cleaved the N-terminal region of annexin A2 at an Asn residue in vitro and in vivo. Recently, we found that transcription of the legumain gene is regulated by the p53 tumor suppressor in HCT116 cells. We and others reported that DJ-1/PARK7, a cancer- and Parkinson's disease-associated protein, works as a coactivator to various transcription factors, including the androgen receptor, p53, PSF, Nrf2, SREBP and RREB1. In this study, we found that expression levels of legumain mRNA and protein and legumain activity were increased in DJ-1-knockout cells. Furthermore, we found that DJ-1 binds to the p53-binding site on intron 1 of the mouse legumain gene in wild-type cells and that cleavage of annexin A2 was increased in DJ-1-knockout cells. These results suggest that legumain expression and activation and cleavage of annexin A2 are regulated by DJ-1 through p53.