タンパク質キナーゼCβとプロリルイソメラーゼ1は,寿命決定因子p66Shccのミトコンドリア効果を調節する

Paolo Pinton¹, Alessandro Rimessi, Saverio Marchi

¹Department of Experimental and Diagnostic Medicine, Section of General Pathology and Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, Ferrera, Italy.

Science (New York, N.Y.)

|February 3, 2007

まとめ

酸化ストレスは,タンパク質キナーゼCβを活性化させ,p66Shcをリン酸化する. このシグナル伝達経路は,p66Shcのミトコンドリアの蓄積を誘発し,アポトーシスと潜在的に老化につながる.

科学分野:

細胞生物学細胞生物学
分子生物学は分子生物学である.
バイオケミストリーバイオケミストリー

背景:

p66Shcは酸化ダメージとアポトーシスの主要な媒介者です.
細胞のストレスをp66Shcのミトコンドリア活動と結びつけるシグナル伝達経路は,以前は知られていなかった.

研究の目的:

ミトコンドリアにおけるp66Shcのプロアポプトティック機能を活性化するシグナル伝達メカニズムを解明する.
細胞ストレスとp66Shc誘発のアポトーシスの関連性を特定する.

主な方法:

p66Shcの活性化とミトコンドリアの局所化におけるタンパク質キナーゼCβとPin1の役割を調査した.
ミトコンドリアカルシウム反応と構造に対するp66Shcの影響を評価した.

主要な成果:

酸化ストレスは,タンパク質キナーゼCβを活性化させ,p66Shcのリン酸化につながります.
Pin1は,リン酸化p66Shcを認識し,ミトコンドリアへのインポートを促進します.
ミトコンドリアのp66Shcは,カルシウム処理を妨害し,ミトコンドリアの構造を変え,アポトーシスを誘発する.

結論:

PKCβとPin1を含む新しいシグナル伝達経路を特定し,p66Shc媒介によるアポトーシスを活性化する.
この経路は,細胞の酸化ストレスをミトコンドリア機能障害と細胞死と結びつける.
特定されたシグナル伝達経路は,高齢化および年齢関連の疾患に対する潜在的な治療目標を表しています.

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