Enzymatic functional analysis for the regulation of circadian rhythm phosphorylation

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K15766
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43040:Biophysics-related
• Research Institution: Hokkaido University (2021-2023); Institute of Physical and Chemical Research (2020)
• Principal Investigator: Shinohara Yuta 北海道大学, 遺伝子病制御研究所, 特任講師 (10755193)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 概日リズム / リン酸化酵素 / 温度補償性 / CKIδ

Outline of Final Research Achievements

The phosphorylation of CKIδ, which determines the period length of the circadian rhythm, is known to exhibit temperature compensated phosphorylation, independent of temperature. In this study, we explored the biological significance of the newly discovered dephosphorylation activity of CKIδ as a novel enzymatic function in the circadian clock. Through screening of peptides derived from the amino acid sequences of clock protein fragments, we identified peptides that promote the dephosphorylation of CKIδ and strongly interact with the PER2 protein domain. These peptides include sequences that influence the period length of the circadian clock, such as the bTrCP domain, suggesting that dephosphorylation may impact the clock's period.

Free Research Field

生物物理、時間生物学

Academic Significance and Societal Importance of the Research Achievements

CKIδはリン酸化酵素であるにも関わらず脱リン酸化活性が起こり酵素活性としての2面性を有する。しかしリン酸化酵素における脱リン酸化活性の意義は明らかにされていない。本研究ではCKIδの脱リン酸化活性機構の分子メカニズムを生物物理学的なアプローチにより明らかにして、概日リズムにおけるCKIδの脱リン酸化活性の意義を結びつけるための、新しい観点を提示できた。