関連する実験動画
Updated: Jun 17, 2026
10:55
Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
デウビキチナゼUSP9XはMCL1を安定させ,腫瘍細胞の生存を促進する
Martin Schwickart1, Xiaodong Huang, Jennie R Lill
1Department of Physiological Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
Nature
|December 22, 2009
まとめ
デウビキチナゼUSP9Xは,がん細胞の生存に不可欠なタンパク質であるMCL1を安定させます. USP9Xを阻害することは,リンパ腫や多発性骨髄腫のような特定の癌の治療に新しい治療戦略を提供することができる.
科学分野:
- 腫瘍学 腫瘍学
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- MCL1は幹細胞と親細胞の生存に不可欠ですが,急速に劣化します.
- リンパ腫と白血病における異常なMCL1過剰発現は,化学抵抗と再発に寄与する.
- がんにおけるMCL1過剰発現を誘発するメカニズムは,依然として不明である.
研究 の 目的:
- MCL1タンパク質の安定性を調節するUSP9Xの役割を調査する.
- USP9XがMCL1依存悪性腫瘍における潜在的な治療標的であるかどうかを判断する.
主な方法:
- USP9XとMCL1.1.の相互作用を調査しました.
- USP9XがMCL1のユビキチン化とプロテアソマル分解に及ぼす効果を分析した.
- ヒトリンパ腫と多発性骨髄腫のサンプルにおけるMCL1レベルと患者の予後との相関USP9X発現.
- USP9XのノックダウンがBH3模倣のABT-737に対するがん細胞の感受性に対する影響を調べました.
主要な成果:
- USP9XはMCL1に直接結合し,分解を標識するユビキチン鎖を取り除き,MCL1.1を安定させる.
- 増加したUSP9X発現は,小胞性リンパ腫および拡散性大B細胞リンパ腫における増加したMCL1タンパク質レベルと相関する.
- 多発性骨髄腫患者の高いUSP9X発現は,予後が悪いことを示している.
- USP9Xのノックダウンにより,MCL1のユビキチン化が増加し,分解が強化され,ABT-737.7による治療で癌細胞死亡が増加します.
結論:
- USP9XはMCL1を安定させ,がん細胞の生存を促進し,多発性骨髄腫の不良予後に貢献します.
- USP9Xは,MCL1依存性がんに対する新しい予後および治療標的を表しています.
- デウビキチナゼは,不安定なオンコプロテインを安定させることができ,がんの発達と進行におけるその役割を強調します.
関連する概念動画
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...
02:58Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
01:13The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
02:18The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.