翻訳後のメカニズムは,哺乳類の昼夜時計を調節する
C Lee1, J P Etchegaray, F R Cagampang
1Department of Neurobiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Cell
|January 10, 2002
まとめ
マウス肝臓のクロックタンパク質 (mPER1, mPER2, CLOCK, BMAL1) は,毎日のリン酸化変化を示しています. 暗号染色体 (mCRY1,mCRY2) は,これらのタンパク質を安定させ,日中リズム調節のための核蓄積を確保するために不可欠です.
科学分野:
- クロノバイオロジーはクロノバイオロジーを用います.
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- シルカディアンリズムとは,約24時間で振動する内生的な生物学的プロセスです.
- 核の分子時計機構には,転写・翻訳のフィードバックループが含まれています.
- リン酸化などの翻訳後の改変は,クロックタンパク質の安定性と機能を調節する上で重要な役割を果たします.
研究 の 目的:
- ネズミの肝臓におけるコアクロックタンパク質の翻訳後の調節を調査する.
- 時計タンパク質の安定性と局所化における暗号染色体 (mCRY1,mCRY2) の役割を明らかにする.
- 時計タンパク質の昼夜調節に関与するキナーゼを特定する.
主な方法:
- ネズミの肝臓におけるクロックタンパク質のリン酸化のインビボ分析.
- タンパク質複合体の形成を研究するための共免疫プレシピテーション.
- クリプトクローム欠乏マウスにおけるクロックタンパク質の行動の分析.
主要な成果:
- マウスのPERIODタンパク質 (mPER1,mPER2),CLOCK,BMAL1は,昼間依存型リン酸化を示しています.
- CLOCK:BMAL1ヘテロダイマーは,日中循環を通じてDNAを結合する.
- 暗号染色体 (mCRY1,mCRY2) は,リン酸化mPER2を安定させ,mPER1,mPER2,およびCKIepsilonの核への侵入を促進するために不可欠です.
- カセインキナーゼIデルタは,新しい時計関連キナーゼとして特定されています.
結論:
- 翻訳後の調節,特にリン酸化は,マウスの肝臓の昼間時計機能を制御する重要なメカニズムです.
- 暗号染色体は,PERIODタンパク質とCKIepsilonの安定性と核の局所化に不可欠です.
- カセインキナーゼIデルタは,哺乳類の昼間時計を調節する既知のキナーゼに大きく加えられています.
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