Yamane Takuya, Kozuka Miyuki, Yamamoto Yoshio, Nakano Yoshihisa, Nakagaki Takenori, Ohkubo Iwao, Ariga Hiroyoshi
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
Department of Health and Nutrition, Faculty of Human Science, Hokkaido Bunkyo University, Eniwa 061-1449, Japan.
Biochem Biophys Rep. 2017 Jan 5;9:187-192. doi: 10.1016/j.bbrep.2016.12.010. eCollection 2017 Mar.
Legumain (EC 3.4.22.34) is an asparaginyl endopeptidase. Legumain activity has been detected in various mouse tissues including the kidney, spleen and epididymis. Legumain is overexpressed in the majority of human solid tumors and transcription of the gene is regulated by the p53 tumor suppressor in HCT116 cells. The legumain activity is also increased under acid conditions in Alzheimer's disease brains. 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. Recently, we found that legumain expression, activation and cleavage of annexin A2 are regulated by DJ-1 through p53. In this study, we found that the expression levels of legumain mRNA were increased in the cerebrum, kidney, spleen, heart, lung, epididymis, stomach, small intestine and pancreas from DJ-1-knockout mice, although legumain activity levels were decreased in the cerebrum, spleen and heart from DJ-1-knockout mice. Furthermore, we found that cystatin E/M expression was increased in the spleen, cerebrum and heart from DJ-1-knockout mice. These results suggest that reduction of legumain activity is caused by an increase of cystatin E/M expression in the spleen, cerebrum and heart from DJ-1-knockout mice.
天冬酰胺内肽酶（EC 3.4.22.34）是一种天冬酰胺基内肽酶。已在包括肾脏、脾脏和附睾在内的多种小鼠组织中检测到天冬酰胺内肽酶活性。天冬酰胺内肽酶在大多数人类实体瘤中过表达，并且在HCT116细胞中该基因的转录受p53肿瘤抑制因子调控。在阿尔茨海默病大脑的酸性条件下，天冬酰胺内肽酶活性也会增加。DJ-1/PARK7是一种与癌症和帕金森病相关的蛋白质，可作为包括雄激素受体、p53、PSF、Nrf2、SREBP和RREB1在内的多种转录因子的共激活因子。最近，我们发现DJ-1通过p53调节天冬酰胺内肽酶的表达、激活以及膜联蛋白A2的裂解。在本研究中，我们发现DJ-1基因敲除小鼠的大脑、肾脏、脾脏、心脏、肺、附睾、胃、小肠和胰腺中天冬酰胺内肽酶mRNA的表达水平升高，尽管DJ-1基因敲除小鼠的大脑、脾脏和心脏中天冬酰胺内肽酶活性水平降低。此外，我们发现DJ-1基因敲除小鼠的脾脏、大脑和心脏中胱抑素E/M的表达增加。这些结果表明，DJ-1基因敲除小鼠的脾脏、大脑和心脏中天冬酰胺内肽酶活性的降低是由胱抑素E/M表达的增加所致。
