Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 467, Issue 3, Pages 472-477Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2015.10.032
Keywords
Legumain; DJ-1; p53; Annexin A2
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Funding
- Scientific Research Fund from Nakagaki Consulting Engineer
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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. (C) 2015 Elsevier Inc. All rights reserved.
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