A metalloprotease regulates the activity of the nuclear receptor REV-ERBs

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K05958
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38060:Applied molecular and cellular biology-related
• 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): 西 英一郎 滋賀医科大学, 医学部, 教授 (30362528)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 概日時計 / 転写制御 / 核内受容体

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 the important roles of NRDC in various homeostasis in vivo. We have recently found that NRDC regulates the mammalian circadian clock via modulating core clock proteins function. The mammalian circadian clockwork is composed of a core feedback loop and additional interlocking loops. Thus, we investigated the role of NRDC on the additional loop, consisting of ROR activators and REV-ERB repressors in this study.

Free Research Field

分子生物学、時間生物学

Academic Significance and Societal Importance of the Research Achievements

今回、NRDCが概日時計のコアループだけではなく、サブループも制御するユニークな時計調節因子である可能性を見出した。