title: 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.
abstract: 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan. Electronic address: t-yamane@pharm.hokudai.ac.jp.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamane
authors.affiliation: Department of Ecology and Molecular Biology, Mie University, Iga, Mie 518-0131, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Center for Research and Development Bioresources, Research Organization for University-Community Collaborations, Osaka Prefecture University, Sakai, Osaka 599-8570, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Institute of Food Sciences, Nakagaki Consulting Engineer and Co., Ltd, Nishi-ku, Sakai 593-8328, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Nakagaki
authors.affiliation: Department of Nutrition, School of Nursing and Nutrition, Tenshi College, Higashi-ku, Sapporo 065-0013, Japan.
authors.forename: Iwao
authors.initials: I
authors.lastname: Ohkubo
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ariga
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D054464:Peroxiredoxins / Q000235:genetics / Q000502:physiology*; D000071617:Protein Deglycase DJ-1; D059748:Proteolysis; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D000099240:Asparaginyl Endopeptidase
chemical_list: D017306:Annexin A2; D003546:Cysteine Endopeptidases; D015513:Oncogene Proteins; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D016159:Tumor Suppressor Protein p53; D000099240:Asparaginyl Endopeptidase; C503466:PARK7 protein, mouse
keywords: Annexin A2; DJ-1; Legumain; p53