p53の特定のDNA結合機能を調節する

T R Hupp¹, D W Meek, C A Midgley

¹Cancer Research Campaign Laboratories, Department of Biochemistry, University of Dundee, Scotland.

Cell

|November 27, 1992

まとめ

腫瘍抑制タンパク質p53は,その機能に不可欠なDNA結合活動を隠しています. この神秘的な活動は,細胞因子によって解き放たれ,細胞の成長と腫瘍抑制を制御する可能性がある.

科学分野:

分子生物学は分子生物学である.
がん研究がん研究
タンパク質生化学タンパク質生化学

背景:

腫瘍抑制タンパク質p53は,がんを予防する上で重要な役割を果たします.
そのDNA結合活動は,腫瘍抑制機能に不可欠である.
p53におけるこのDNA結合活動は,暗号的または潜在的であることが観察されています.

研究の目的:

p53.3の謎のDNA結合活性を調節するメカニズムを調査する.
p53 DNA結合を活性化できる細胞の因子や条件を特定する.
腫瘍抑制のためのp53DNA結合活性化の影響を理解するために.

主な方法:

ゲル移動シフトアッセイを使用してDNA結合を評価しました.
再結合野生型ヒトp53とモノクローナル抗体を使用した.
C端末の改変,タンパク質分解,E. coli dnaK,およびカゼインキナーゼIIがp53DNA結合に及ぼす影響を調査した.

主要な成果:

再結合野生型ヒトp53は,弱く,配列特異的なDNA結合を示した.
C端を標的としたモノクローナル抗体は,ステキオメトリック的にp53の暗号的DNA結合を活性化させた.
また,C端末の消去,軽度のタンパク質分解,E. coli dnaK,およびカゼインキナーゼII媒介のリン酸化によって活性化が達成されました.

結論:

p53のDNA結合活動は,そのC端末ドメインによって調節され,様々な細胞機構によって活性化することができます.
細胞因子によるp53DNA結合の活性化は,細胞成長停止を含む,その腫瘍抑制機能にとって極めて重要である可能性が高い.
これらの規制メカニズムの理解は,がん予防におけるp53の役割についての洞察を提供します.

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