雌激醇介导的ERα激活和随后的PR和GREB1诱导的相互依赖性,以控制细胞周期进展
M M Heldring1, B Duijndam1,2, A Kyriakidou1
1Division of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, the Netherlands.
Heliyon
|November 25, 2024
概括
这项研究模拟了雌激素如何影响蛋白质动力学和细胞周期进展. 数学模型揭示了雌激素受体α和像GREB1这样的蛋白质之间的关键相互作用,影响细胞增殖.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 计算生物学 计算生物学
背景情况:
- 干扰内分泌的化学物质可以干扰细胞发育和平衡.
- 雌激素对细胞内蛋白质动态和细胞增殖的影响需要定量理解.
研究的目的:
- 开发一种描述转录因子动态和细胞循环调节对雌激素反应的数学模型.
- 研究雌激素受体α (ERα) 信号与细胞周期进展之间的关系.
主要方法:
- 在17β-雌二醇 (E2) 与ERα结合时开发了GREB1,PR和TFF1蛋白质动态的数学模型.
- 使用MCF7细胞的成像数据对模型进行校准,以分析蛋白质表达动态.
- 整合了ER信号模型与细胞周期模型,并使用核跟踪和深度神经网络图像分割进行了验证.
主要成果:
- 模型校准表明GREB1和PR的转录激活取决于与这些蛋白质的E2-ERα复合体关联.
- 综合模型预测了GREB1和PR敲除对细胞周期进展的影响.
- 提供了对ERα调节蛋白及其在细胞循环调节中的作用的机制性见解.
结论:
- 开发的模型提供了对雌激素对蛋白质动态和细胞增殖的影响的定量描述.
- 这些发现为研究内分泌干扰化学物质的药理动力学提供了基础.
- 阐明了对ERα信号传递和细胞周期控制的机制性见解.
相关概念视频
Mitogens and the Cell Cycle
6.4K
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...
6.4K
Negative Regulator Molecules
35.2K
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.
35.2K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
Inhibition of Cdk Activity
4.7K
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...
4.7K
Proliferative Phase
379
The proliferative phase typically occurs after menstruation and lasts between 6 to 13 days in a standard 28-day cycle. This phase involves the reconstruction of the endometrium, guided by estrogen produced by the developing ovarian follicle.
Notably, the stratum basale, the basal layer of the endometrium, including the basal parts of the uterine glands, remains unaffected by menstruation. Stem cells in this layer undergo mitosis, regenerating the stratum functionalis and thickening the...
Notably, the stratum basale, the basal layer of the endometrium, including the basal parts of the uterine glands, remains unaffected by menstruation. Stem cells in this layer undergo mitosis, regenerating the stratum functionalis and thickening the...
379


