Rbx1は,VHL腫瘍抑制複合体とSCFユビキチンリガゼの成分である

T Kamura¹, D M Koepp, M N Conrad

¹Howard Hughes Medical Institute, Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.

Science (New York, N.Y.)

|April 24, 1999

まとめ

フォン・ヒッペル・リンダウ (VHL) 腫瘍抑制タンパク質複合体はRbx1を含み,VHLを細胞のユビキチネーションと結びつける. この発見は,VHLの理解を深める.

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
細胞生物学細胞生物学

背景:

フォン・ヒッペル・リンダウ (VHL) 腫瘍抑制遺伝子は,ヒトの腎臓がんで頻繁に変異する.
VHLタンパク質は,エロンギンB,エロンギンC,クリン-2を含む,転写の延長とユビキチン化に関与する複合体の中で機能する.
癌の病原性におけるVHL複合体の役割は,タンパク質分解経路におけるその機能と関連しています.

研究の目的:

固有のVHL複合体の完全な組成を調べる.
VHL複合体内の新しいタンパク質相互作用を特定する.
細胞プロセスにおけるVHL複合体の構成の機能的影響を明らかにする.

主な方法:

ネズミの肝臓からのVHL複合体の免疫圧縮.
関連するタンパク質を特定するための質量スペクトロメトリ.
イーストユビキチンリガゼ複合体との比較分析.

主要な成果:

ネズミの肝臓の内生的なVHL複合体は,Rbx1を含み,RING-H2の指のようなモチーフを持つ保存されたタンパク質である.
Rbx1はカリンズと相互作用し,ユビキチネーションのための基質採用における役割を示唆しています.
Rbx1の酵母ホモログは,SCF ((Cdc4)) のユビキチンリガゼの重要な成分であり,細胞サイクル進行を調節する.

結論:

VHL複合体の構成は,Rbx1.1を含む,これまで知られているものよりもより広範です.
Rbx1の含有により,VHL腫瘍抑制器とコアユビキチネーション機構の間の直接的なリンクが確立される.
これらの発見は,腫瘍抑制と細胞周期調節におけるVHL機能の基礎となる分子機構に関する新しい洞察を提供します.

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