B-サイクリンmRNAの安定性を制御することにより,M相のタイミングを決定する栄養素反応経路
Vincent Messier1, Daniel Zenklusen, Stephen W Michnick
1Département de Biochimie, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Québec H3C 3J7, Canada.
Cell
|May 28, 2013
まとめ
酵母細胞サイクル進行は,CLB2 mRNAレベルを調節することに依存しています. タンパク質Hmt1はCLB2mRNAを安定させ,その活動はDbf2キナーゼとPph22フォスファターゼによって制御され,栄養素の変化中に細胞分裂に影響を与えます.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
背景:
- 細胞サイクルの進行には,栄養素の利用可能性などの環境のシグナルに反応する遺伝子発現の正確な調節が必要です.
- M相サイクリンCLB2は,酵母における細胞分裂の重要な調節剤である.
- アルギニンのメチル化のような翻訳後の改変は,タンパク質の機能とmRNAの安定性を調節する役割を果たします.
研究 の 目的:
- 栄養分レベルに応じてCLB2 mRNAの蓄積が調節されるメカニズムを調査する.
- CLB2 mRNAの安定性を制御する重要なタンパク質とその調節相互作用を特定する.
- M相サイクリン調節におけるアルギニンメチルトランスファーゼHmt1の役割を明らかにする.
主な方法:
- 酵母遺伝学と分子生物学技術が採用されました.
- 北部ブラッティングと定量PCRを用いたCLB2mRNAレベルの分析.
- タンパク質とタンパク質の相互作用と酵素活動 (キナーゼ,フォスファタゼ,メチルトランスフェラーゼ) の調査.
- 栄養不足とTOR阻害が細胞サイクル進行に及ぼす影響に関する研究.
主要な成果:
- CLB2 mRNAの蓄積は,異質な核RNA結合タンパク質 (hnRNP) アルギニンメチルトランスフェラーゼであるHmt1の組み立てと活性化に依存しています.
- Hmt1の活動はキナーゼDbf2によって促進され,PP2AフォスファターゼPph22によって抑制されます.
- 活性化されたHmt1は hnRNPをメチル化し,CLB2トランスクリプトの安定化につながります.
- Dbf2媒介によるHmt1の活性化は協力的であり,Pph22の脱リン酸化は段階的に行われ,敏感な調節が可能である.
- 栄養素の飢餓とTOR阻害はPph22を活性化し,CLB2の枯渇とM相の遅延につながります.
結論:
- Hmt1媒介の hnRNPメチル化によるCLB2 mRNAの安定性を制御する新しい調節経路が特定されました.
- Dbf2キナーゼとPph22フォスファターゼの活性とのバランスは,Hmt1の機能を微調整し,それによって細胞サイクル進行を調節します.
- このメカニズムにより,酵母細胞はM相への入り口を栄養素の利用に適応させ,子細胞の生存能力を確保できます.
- この発見は,Pph22活性がサイクリンmRNAの安定性を調節し,細胞サイクル進行を環境条件と結びつける一般的なモデルを提案しています.
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