p21はサイクリンキナーゼの普遍的阻害剤である
1Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.
Nature
|December 16, 1993
まとめ
タンパク質p21は,細胞増殖の調節に不可欠なサイクリン依存キナーゼ (CDK) の普遍的阻害剤として作用する. 変形した細胞におけるその喪失は,癌の発達と細胞サイクル制御における重要な役割を果たすことを示唆している.
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
- 腫瘍学 腫瘍学
背景:
- 細胞増殖の緩和は,腫瘍変異の重要な特徴です.
- 変化した成長制御経路は細胞サイクル機構に影響するが,そのメカニズムは不明である.
- ウイルス性オンコタンパク質は,変異細胞のサイクリン依存キナーゼ (CDK) コンプレックスに変化を誘導する.
研究 の 目的:
- 変形した細胞CDK複合体における増殖細胞核抗原 (PCNA) とp21喪失の重要性を調査する.
- 細胞サイクル調節におけるp21の役割を明らかにする.
- 四次細胞サイクルキナーゼ複合体を in vitro で再構成する.
主な方法:
- p21遺伝子の分子クローン.
- 四次細胞サイクルキナーゼ複合体のインビトロ再構成.
- サイクリン/CDK活性と細胞増殖に対するp21の影響を測定するアッセイ.
主要な成果:
- p21がクローンされ,細胞サイクル調節におけるその役割が調査されました.
- p21は,テストされたすべてのサイクリン/CDKファミリーメンバーの活動を抑制することが判明しました.
- p21の過剰発現は,哺乳類の細胞における増殖を抑制した.
結論:
- p21は,サイクリンキナーゼの普遍的阻害剤として作用する.
- 変形した細胞におけるCDK複合体からのp21の喪失は,制御不能な増殖に寄与する可能性があります.
- p21は細胞循環の重要な調節体であり,がん治療における潜在的な標的である.
関連する概念動画
01:45Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
02:39Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
00:50Anaphase Promoting Complex
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
02:34Inhibition of CDK Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...