hSIR2 (((SIRT1) はNAD依存型p53デセチラゼとして機能する

H Vaziri¹, S K Dessain, E Ng Eaton

¹Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Cell

|October 24, 2001

まとめ

人間の遺伝子hSIR2 (SIRT1) は,タンパク質を脱酸化し,腫瘍抑制剤p53.3を抑制する. この脱酸化はp53を調節する.

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:

DNA損傷はp53アセチル化を誘発し,細胞成長停止またはアポトーシスにつながる.
酵母Sir2のヒト同型であるhSIR2 (SIRT1) タンパク質は,老化とDNA損傷反応に関与しています.

研究の目的:

hSIR2 (SIRT1) がp53タンパク質の活性を調節する役割を調査する.
hSIR2 (SIRT1) がp53.3と直接相互作用し,p53.3を修正するかどうかを判断する.

主な方法:

人間の細胞におけるhSIR2 (SIRT1) とp53の相互作用を研究した.
野生型および触媒的に無活性なhSIR2 (SIRT1) がp53の転写活性に与える影響を評価した.
測定されたp53-依存アポトーシスと放射線感受性.

主要な成果:

hSIR2 (SIRT1) はp53に結合し,p53を脱酸化し,特にC端末のLys382残基に結合する.
野生型hSIR2 (SIRT1) の発現は,p53の転写活動を低下させます.
不活性なhSIR2 (SIRT1) は,p53-依存アポトーシスと放射線感受性を強化する.

結論:

hSIR2 (SIRT1) は,脱エチル化を介してp53の機能を否定的に調節する.
SIRT1は,p53の活性を調節することによって,DNA損傷応答経路において重要な役割を果たします.

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