A metalloprotease regulates the circadian clock

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08536
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Kobe Gakuin University
• Principal Investigator: HIRAOKA yoshinori 神戸学院大学, 薬学部, 助教 (60397552)
• Co-Investigator(Kenkyū-buntansha): 久米 典昭 神戸学院大学, 薬学部, 教授 (20252455) ; 西 英一郎 滋賀医科大学, 医学部, 教授 (30362528)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 概日時計 / 時計遺伝子 / 転写制御

Outline of Final Research Achievements

Nardilysin (N-arginine dibasic convertase; NRDC) is a zinc peptidase of the M16 family. We have reported that NRDC has multiple functions, which depend on its cellular localization. In the extracellular space, NRDC enhances ectodomain shedding of a variety of membrane proteins. On the other hand, NRDC in the nucleus works as a transcriptional coregulator. These findings suggest important roles of NRDC in various homeostasis in vivo. To evaluate the role of NRDC in the nucleus in more detail, we performed ChIP-seq of NRDC in mouse liver. ChIP-seq and motif analysis of the NRDC-binding sites revealed a significant enrichment for E-box motif. Thus, we investigated the role of NRDC on the mammalian circadian clock in the present study.

Free Research Field

時間生物学

Academic Significance and Societal Importance of the Research Achievements

これまで生物時計とは何の関連も指摘されていなかったNRDCが、概日リズムを制御する新規時計調節因子である可能性を見出した。