Rbf/E2F1通过在Drosophila前列腺类二次细胞中的类固醇独立Ecdysone受体信号传递来控制生长和内核复制
Aashika Sekar1, Aaron Leiblich1,2, S Mark Wainwright1
1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
PLoS genetics
|June 26, 2023
概括
在类动物中,视网母细胞瘤蛋白 (Rbf) 和E2F1调节辅助腺细胞中的交配诱导的细胞生长和内核复制. 这一由Ecdysone受体 (EcR) 控制的过程反映了割抵抗性前列腺癌 (CRPC) 中的荷尔蒙独立信号.
科学领域:
- 细胞生物学 细胞生物学
- 发育生物学是发展生物学.
- 分子生物学分子生物学
背景情况:
- 视网母细胞瘤 (Rb) 瘤抑制基因的丧失和E2F1激活是前列腺癌的晚期事件,导致前列腺癌 (CRPC) 的进展.
- 在Drosophila melanogaster雄性辅助腺二次细胞 (SCs) 在交配时,从类固醇依赖到类固醇独立的Ecdysone Receptor (EcR) 控制表现出生理上的切换,诱导内核复制以补充分泌区.
研究的目的:
- 为了研究Drosophila Rb同类物 (Rbf) 和E2F1在调节SC生长和内核复制中的依赖交配的开关中的作用.
- 阐明这种交换机背后的分子机制及其与CRPC相似之处.
主要方法:
- 在Drosophila中对Rbf,E2F1,Cyclin D (CycD),Cyclin E (CycE) 和Ecdysone受体 (EcR) 的遗传操纵.
- 对男性辅助腺二次细胞中的细胞增殖,双核和内核复制的分析.
- 通过Decapentaplegic (Dpp) 调查骨形态遗传蛋白 (BMP) 信号传递的参与.
主要成果:
- 发现过多的Rbf活性可逆地抑制SC双核化.
- Rbf,E2F1,CycD和CycE被确定为依赖交配的SC内核复制和生长的关键调节者.
- CycD/Rbf/E2F1轴需要EcR信号 (但不是ecdysone) 来诱导依赖CycE的内核复制和生长,模仿CRPC变化.
- 由DPP介导的BMP信号与CycD/Rbf/E2F1通路相交,以驱动内核复制.
结论:
- 一个涉及Rbf,E2F1,CycD,CycE和EcR的信号开关能够实现快速的交配诱导的SC生长和分泌,而不依赖于先前的雌性暴露.
- 这种Drosophila模型揭示了与CRPC中观察到的病理性荷尔蒙独立AR信号的机制平行,这表明了保留的调节途径.
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