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血清供应的Wnt3a信号诱导培养细胞中的复制应激
Ying Wang1,2, Rui Wang3, Haiying Ma1,2,4
1Department of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
Biochemistry and biophysics reports
|August 21, 2023
概括
用血清激活Wnt信号增强了53BP1的酸化,触发了DNA损伤反应和细胞循环停止. 没有血清的Wnt信号不会激活这种通路,突出显示血清.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- Wnt信号对于发育和平衡至关重要,放松监管与癌症等疾病有关.
- 蛋白质酸化是Wnt信号传递的一个关键的翻译后修饰,通常在血清缺乏条件下进行研究.
- 血清饥饿的条件可能会忽视Wnt信号在生理环境中的综合效应.
研究的目的:
- 为了研究Wnt3a条件介质 (CM) 用血清供应治疗的时间蛋白质组动态.
- 在生理学上相关的条件下识别关键的酸化事件及其功能后果.
主要方法:
- 用血清治疗Wnt3a CM后的蛋白质组变化的蛋白质组学分析.
- 蛋白质组动态的时间概况.
- 功能性测试用于评估DNA损伤反应和细胞周期进展.
主要成果:
- 确定了三种不同的蛋白质组变化的集群,其时间概况影响基因表达和染色体组织.
- 在Thr543中观察到53BP1的增强酸化,这是DNA损伤反应中的关键事件.
- 通过γH2AX和Chk1激活,证明了Wnt3a诱导的复制应激反应,导致S相减少,在无血清条件下没有这种情况.
结论:
- 血清供应对于53BP1-Chk1复制应激反应通路的Wnt3a介导激活至关重要.
- 在血清补充条件下的蛋白组分析揭示了对Wnt信号传递的生理作用的新见解.
- 血清的存在或不存在显著影响Wnt信号通路激活和细胞结果.
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