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相关概念视频

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

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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...
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Positive Regulator Molecules02:39

Positive Regulator Molecules

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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.
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M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

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Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
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Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

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Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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The Cell Cycle Control System02:11

The Cell Cycle Control System

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The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
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Negative Regulator Molecules01:23

Negative Regulator Molecules

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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.
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相关实验视频

Updated: Jun 14, 2025

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
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环素A/B RxL宏环抑制剂用于治疗具有高E2F活性的癌症.

Shilpa Singh, Catherine E Gleason, Min Fang

    bioRxiv : the preprint server for biology
    |August 30, 2024
    PubMed
    概括

    新的宏环抑制剂通过阻断环素A/B相互作用,选择性地杀死小细胞肺癌 (SCLC) 细胞,通过螺旋组装检查点激活导致细胞亡. 这些抑制剂显示出作为一种新型SCLC治疗的前景.

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    Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
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    Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
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    Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

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    相关实验视频

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    Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
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    Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
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    科学领域:

    • 分子瘤学分子瘤学
    • 癌细胞生物学 癌细胞生物学
    • 药物发现 药物发现

    背景情况:

    • 精确控制E2F1活动对于癌细胞增殖至关重要;过度的E2F1活动会引发亡.
    • 小细胞肺癌 (SCLC) 经常表现出高E2F1活性,呈现出治疗脆弱性.

    研究的目的:

    • 开发针对环林A/B相互作用的细胞透性和生物可用宏循环.
    • 研究这些宏环抑制剂在SCLC中的作用机制和治疗潜力.

    主要方法:

    • 细胞透性宏循环的发展,抑制RxL介导的环林A和环林B的相互作用.
    • 全基因组的CRISPR/Cas9淘汰和随机突变发生查以确定抵抗机制.
    • 基础编辑器屏幕分析影响抑制剂反应的环林B变体.
    • 在患者衍生的SCLC异种移植模型中对口服生物可用宏循环的评估.

    主要成果:

    • 大环抑制剂 (cyclin A/Bi) 通过阻断cyclin A/B相互作用,选择性地杀死SCLC细胞.
    • 环素A/Bi通过螺旋组合检查点 (SAC) 激活诱导亡,依赖于环素B和Cdk2.
    • 抑制剂过度激活E2F1和环林B,导致线粒细胞死亡.
    • 口服生物可用的cyclin A/Bi在耐化疗SCLC异种移植中显示出强大的瘤生长抑制.

    结论:

    • 环素A/Bi通过新的功能获取机制,在具有高E2F活性的癌症中诱导细胞亡.
    • 这些发现表明,cyclin A/Bi作为SCLC和其他E2F1驱动癌症的有希望的治疗策略.