I カッパB:NF-カッパB転写因子の特定の阻害剤である

P A Baeuerle¹, D Baltimore

¹Whitehead Institute for Biomedical Research, MA 02142.

Science (New York, N.Y.)

|October 28, 1988

まとめ

タンパク質阻害剤であるI kappa Bは,細胞質のNF-kappa B転写因子を結合する. フォルボールのエステルは,活性なNF-カッパBを放出し,核に入り,遺伝子発現を活性化する.

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
免疫学免疫学とは

背景:

核因子カッパB (NF-カッパB) は,免疫反応と細胞調節に不可欠な転写因子です.
NF-kappa Bの活動は厳しく管理されていますが,その規制の正確なメカニズムはまだ調査中です.
NF-kappa Bの調節を理解することは,細胞の信号伝達経路を理解する鍵です.

研究の目的:

NF-kappa B.のDNA結合活動と細胞下局所化を調節するメカニズムを調査する.
非発現細胞におけるNF-kappa Bに関連した抑制タンパク質を特定する.
NF-kappa B.を活性化するホルボールエステルの役割を明らかにする.

主な方法:

タンパク質の局所を決定するための細胞分化および核分裂実験.
解離剤の存在下でのDNA結合活動を評価するための生化学分析.
NF-kappa Bと相互作用する抑制タンパク質 (I kappa B) の特徴.

主要な成果:

NF-カッパBは,60〜70 kDaの抑制タンパク質 (I カッパB) に結合した細胞溶液分泌物で発見される.
カッパBは特にNF-カッパBのDNA結合活動を逆転的に抑制する.
フォルボールのエステル治療は,おそらくタンパク質キナーゼC経由で,イカッパBの改変を引き起こし,核転位のための活性NF-カッパBを放出します.

結論:

NF-kappa BとI kappa Bの細胞質複合体は,NF-kappa Bの活動を調節する.
フォルボールのエステルはNF-カッパBをI-カッパBから分離して活性化させ,核転位を可能にします.
この研究は,転写因子の活性と局所化を制御するホルボールエステル反応性規制機構を明らかにしています.

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