Jove
Visualize
お問い合わせ
JoVE
x logofacebook logolinkedin logoyoutube logo
JoVEについて
概要リーダーシップブログJoVEヘルプセンター
著者向け
出版プロセス編集委員会範囲と方針査読よくある質問投稿
図書館員向け
推薦の声購読アクセスリソース図書館諮問委員会よくある質問
研究
JoVE JournalMethods CollectionsJoVE Encyclopedia of Experimentsアーカイブ
教育
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab Manual教員リソースセンター教員サイト
利用規約
プライバシーポリシー
ポリシー

関連する概念動画

Negative Regulator Molecules01:23

Negative 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.
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Inhibition of Cdk Activity02:34

Inhibition 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...
Abnormal Proliferation02:23

Abnormal 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...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...

こちらも読む

関連記事

共著者、ジャーナル、引用グラフによってこの研究に関連する記事。

並び替え
Same author

Deciphering the Role of Cancer Stem Cells in Breast Cancer Brain Colonization Using a Novel Patient-Derived Model.

Advanced healthcare materials·2026
Same author

FAK signaling pathways are modulated by HSPB8 and BAG3 in breast cancer.

Cell communication and signaling : CCS·2026
Same author

SH3BP5L triggers the RAB11A-regulated integrin recycling network implicated in breast cancer metastasis.

The Journal of clinical investigation·2026
Same author

Inter-Assay Variability of TROP2 Immunohistochemistry in Triple-Negative Breast Cancer.

Molecular diagnosis & therapy·2025
Same author

The CRL7<sup>FBXW8</sup> Complex Controls the Mammary Stem Cell Compartment through Regulation of NUMB Levels.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)·2025
Same author

Cancer cell stiffening via CoQ<sub>10</sub> and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer.

Nature communications·2024

関連する実験動画

Updated: Jun 30, 2026

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method
09:32

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method

Published on: September 10, 2017

NUMBはp53の腫瘍抑制活性を制御する.

Ivan N Colaluca1, Daniela Tosoni, Paolo Nuciforo

  • 1IFOM, the FIRC Institute for Molecular Oncology Foundation, Via Adamello 16, 20139, Milan, Italy.

Nature
|January 4, 2008
PubMed
まとめ

乳がんにおけるNUMBタンパク質喪失は,腫瘍遺伝子のNOTCHを活性化し,p53腫瘍抑制経路を弱める. この二重効果は,攻撃的な腫瘍フェノタイプと悪い予後を促進し,新しい腫瘍抑制機構を明らかにします.

科学分野:

  • 細胞生物学 細胞生物学
  • 癌生物学 癌生物学について
  • 分子腫瘍学 分子腫瘍学

背景:

  • NUMBは,NOTCHシグナル伝達を調節する細胞運命決定因子として知られており,乳がんにおける腫瘍抑制作用を有しています.
  • NUMBの腫瘍抑制機能の基礎となる正確な分子機構は,まだ完全に理解されていません.

研究 の 目的:

  • 腫瘍タンパク質p53 (TP53) の安定性と活性を調節するヒトNUMBの新たな機能を明らかにする.
  • 乳がんにおけるNUMB喪失の結果,特にp53とNOTCH経路への影響を調査する.

主な方法:

  • バイオケミカルアッセイを使用して,p53とE3ユビキチンリガゼHDM2 (MDM2) とのNUMBの相互作用を調査しました.
  • 乳がん原発細胞におけるp53タンパク質のレベル,活動,および下流フェノタイプに対するNUMB発現レベルの影響を評価した.
  • NUMB喪失の文脈で,NOTCH経路の活性と化学抵抗を分析した.

主要な成果:

  • 発見されたNUMBは,p53とHDM2との三重複合体を形成し,p53のユビキチン化と分解を阻害し,p53を安定させ,p53を安定させる.
  • 乳がんにおけるNUMB発現の喪失は,p53のレベルが低下し,化学抵抗性が増加することを示した.
  • NUMBの喪失は同時にNOTCH受容体の活性を増大させ,攻撃的な腫瘍フェノタイプと悪い予後につながることを示した.

さらに関連する動画

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

関連する実験動画

Last Updated: Jun 30, 2026

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method
09:32

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method

Published on: September 10, 2017

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

結論:

  • NUMBは,p53タンパク質を安定させることで,p53腫瘍抑制経路の重要な調節体として作用します.
  • 乳がんにおけるNUMBの喪失は,同時にp53経路を無効化し,腫瘍性NOTCH経路を活性化します.
  • NUMBの喪失によって引き起こされるこの二重の非活性化/活性化メカニズムは,攻撃的な乳がんの進行に貢献する新しい腫瘍抑制回路を確立します.