塞维巴布林诱导异常的管原纤维的聚合,通过与Vinblastine位点和第七位点结合
Peng Bai1, Wei Yan1, Jianhong Yang1
1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Cytoskeleton (Hoboken, N.J.)
|December 5, 2023
概括
塞维巴布林结合到两个微管位点,诱导异常的管原纤维聚合,这是一个新的效应. 这一发现为突蛋白的动态和潜在的癌症疗法提供了洞察力.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 微管是细胞必不可少的组成部分,也是化疗的关键点.
- 管素异构体形成微管,并具有多个药物结合点.
- 塞维巴布林是独特的,它可以同时结合到蛋白上的Vinblastine和Seventh位点.
研究的目的:
- 调查塞维巴布林结合温布拉斯和第七位点的相互作用细胞效应.
- 为了阐明塞维帕布林诱导的突改变背后的机制.
主要方法:
- 免疫光显微镜的使用方法
- 传输电子显微镜的使用
- 具有竞争约束力的分析.
- 位点定向的突变发生 (αY224G)
主要成果:
- 塞维巴布林结合到这两个位点诱导了异常的管原体纤维的聚合,形成线性原体纤维和不规则的聚合物.
- 这种聚合效应需要同时结合Vinblastine和第七位点.
- 与针对这些部位的药物同时治疗模仿了塞维巴布林的效果,这表明一种保存机制.
结论:
- 塞维巴布林通过在两个不同的位点进行交互性结合,诱导一种新的状管体形态.
- 这一发现为微管的动态不稳定性提供了新的见解.
- 这项研究指导了进一步调查塞维巴布林作为潜在的治疗剂.
相关概念视频
Drugs that Destabilize Microtubules
2.0K
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
Drugs that Stabilize Microtubules
2.1K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.1K
Mechanism of Filopodia Formation
2.4K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.4K
Cancer Cell Migration through Invadopodia
2.3K
Invadosome is a broad category of cell surface structures with proteolytic activity that degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.3K
Actin Filament Depolymerization
3.1K
Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
In F-actin, the ADF/cofilin proteins...
3.1K
Inhibition of Cdk Activity
4.8K
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...
4.8K


