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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
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  1. ホーム
  2. Eprsは,マウスの肥満に影響を与える重要なmtorc1-s6k1エフェクターである.
  1. ホーム
  2. Eprsは,マウスの肥満に影響を与える重要なmtorc1-s6k1エフェクターである.

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Body Composition and Metabolic Caging Analysis in High Fat Fed Mice
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EPRSは,マウスの肥満に影響を与える重要なmTORC1-S6K1エフェクターである.

Abul Arif1, Fulvia Terenzi1, Alka A Potdar2

  • 1Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.

Nature
|February 9, 2017

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まとめ
この要約は機械生成です。

科学者はmTORC1-S6K1経路によって調節される 肥満と老化の重要な要因として グルタミルプロリルtRNA合成酵素 (EPRS) を発見しました 脂肪の代謝と寿命を制御する

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科学分野:

  • 細胞生物学
  • メタボリズム
  • 老化に関する研究

背景:

  • 哺乳類におけるラパミシン複合体1 (mTORC1) とp70リボソームタンパク質S6キナーゼ1 (S6K1) 経路の標的は,肥満と老化に関連した代謝プロセスを調節する.
  • mTORC1-S6K1のターゲットに関する既存の知識は,観察された機能喪失のフェノタイプを完全に説明できず,追加の下流効果因子の存在を示しています.

研究 の 目的:

  • 代謝調節に関与するmTORC1-S6K1経路の新しい下流効果因子を特定する.
  • 脂肪化と老化におけるグルタミルプロリルtRNA合成酵素 (EPRS) のリン酸化の役割を調査する.

主な方法:

  • フォスフォ欠乏性 (S999A) とフォスフォ模倣性 (S999D) EPRS変異を持つノックインマウスを生成した.
  • ミュータントマウスにおける体重,脂肪組織質量,寿命を含む,評価された代謝表型.
  • リン酸化EPRS (リン酸化EPRS) の結合パートナーを特定するために相互作用スクリーニングを行った.

主要な成果:

  • ホモジゴスS999Aマウスは体重が減り,脂肪組織が減少し,寿命が延びた.
  • mTORC1-S6K1によるSer999でのEPRSのリン酸化により,アミノアシルtRNAマルチシンセテーゼ複合体から放出されます.
  • 脂肪酸輸送タンパク質1 (FATP1) に結合し,脂肪酸の吸収を促進する.
  • 結論:

    • EPRSは新しいmTORC1-S6K1標的であり,肥満と老化に大きく影響する.
    • EPRSのリン酸化は,S6K1依存の代謝反応の重要な媒介である.
    • EPRSとFATP1の相互作用は,代謝調節におけるmTORC1- S6K1経路の重要な終端エフェクターメカニズムを表しています.