RACK1とタンパク質キナーゼカルファを哺乳類の昼夜時計の不可欠な構成要素として特定
Maria S Robles1, Cyril Boyault, Darko Knutti
1Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
まとめ
シルカディアン・クロックです.
科学分野:
- 分子生物学は分子生物学である.
- クロノバイオロジーはクロノバイオロジーを用います.
- バイオケミストリー バイオケミストリー
背景:
- 哺乳類の昼間時計は,CLOCK-BMAL1転写因子を含む負のフィードバックループに依存しています.
- このフィードバックループの分子メカニズムを理解することは,日中リズム調節の解読に不可欠です.
研究 の 目的:
- 昼間のフィードバックフェーズ中にBMAL1に関連したタンパク質複合体を調査する.
- 哺乳類の昼間時計における活性化Cキナーゼ-1 (RACK1) とタンパク質キナーゼC-アルファ (PKCalpha) の受容体の役割を明らかにする.
主な方法:
- BMAL1.1.を含むマウス核タンパク質複合体の分析
- 線維芽細胞におけるRACK1とPKCalphaの過剰発現と枯渇に関する研究.
- PKCalpha.によるBMAL1の改変を評価するためのインビトロリン酸化アッセイ.
主要な成果:
- RACK1とPKCalphaは,核BMAL1複合体内で昼夜依存の方法で特定されました.
- RACK1とPKCalphaの過剰発現は,CLOCK-BMAL1の転写活動を抑制しました.
- RACK1はPKCalpha媒介によるBMAL1のリン酸化をインビトロで強化した.
- RACK1またはPKCalphaの枯渇は,線維芽細胞における昼夜周期の短縮につながった.
結論:
- タンパク質キナーゼC (PKC) 信号伝達経路は,日中時計内で動的に調節されます.
- RACK1とPKCalphaは,哺乳類の昼夜フィードバックループの不可欠な構成要素であり,時計の振動に影響を与えます.
- PKC経路は,外部刺激だけでなく,細胞内プロセスによってリズム的に活性化され,昼夜リズムに寄与します.
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