哺乳類の紫外線反応: c-Jun誘導は,p53による成長停止から脱出するために必要である

E Shaulian¹, M Schreiber, F Piu

¹Laboratory of Gene Regulation and Signal Transduction University of California, San Diego 9500 Gilman Drive 92093, La Jolla, CA, USA.

Cell

|January 4, 2001

まとめ

タンパク質"c-Jun"は,紫外線で照射された細胞が細胞サイクルに戻るのを助けます. しかし,紫外線反応において極めて重要なp53とp21を否定的に調節することにより,アポトーシスを促進します.

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
遺伝学遺伝学とは

背景:

哺乳類の紫外線反応は,典型的にはミトゲンシグナルに関連しているプロトオンコゲンであるc-Junの急速な誘導を含む.
遺伝子毒性物質によって成長停止を引き起こすc-Junの誘発は矛盾しているようです.
紫外線反応におけるc-Junの役割を理解することは,細胞損傷と修復メカニズムを理解するために不可欠です.

研究の目的:

マウスの線維芽細胞における紫外線反応経路におけるc-Junの特定の機能を解明する.
紫外線照射後のc-Junが細胞サイクル進行とアポトーシスに影響するメカニズムを調査する.
紫外線反応におけるc-Junの役割が,電離放射線に対する反応におけるその役割と異なるかどうかを判断する.

主な方法:

c-Junが欠けているマウスの線維芽細胞と,構成的なc-Jun発現を持つ細胞を使用した.
紫外線照射後の細胞サイクル再エントリーとアポトーシスの割合を分析した.
c-Jun,p53,およびp21プロモーターの相互作用を調査しました.

主要な成果:

c-Junは,紫外線で照射された細胞の細胞サイクル復帰には不可欠ですが,電離放射線反応には不可欠ではありません.
c-Junが欠けている細胞は,細胞サイクルを長期にわたって停止し,アポトーシスに対する抵抗を示します.
構成的なc-Jun発現は,細胞サイクル停止の失敗とアポトーシスの増加につながります.
c-Junは,p21プロモーターへのp53結合を否定的に調節し,p21誘導レベルに影響を与えます.

結論:

c-Junは,紫外線損傷後の細胞運命を決定する際に重要な役割を果たし,細胞サイクル停止とアポトーシスのバランスをとります.
このメカニズムはp53-p21経路を調節し,c-Junがミトゲネシスを超えた複雑な役割を強調する.
これらの発見は,DNA損傷反応経路と潜在的な治療目標についての洞察を提供します.

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