在细胞衰老过程中,Ets和Id蛋白对p16INK4a表达产生相反的影响
N Ohtani1, Z Zebedee, T J Huot
1Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Nature
|March 10, 2001
概括
转录因子Ets1和Ets2调节p16INK4a的表达,这是细胞衰老和瘤抑制的关键因素. 它们的活动受到信号通路和与Id1的相互作用的影响,导致细胞生长停止.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- p16INK4a是一种循环素依赖的激酶抑制剂,对复制性衰老和瘤抑制至关重要.
- 控制p16INK4a在衰老中的表达及其作为瘤抑制剂的作用的机制尚未完全理解.
研究的目的:
- 研究Ets1和Ets2转录因子在调节p16INK4a表达中的作用.
- 阐明控制人体双胞胎纤维细胞中p16INK4a促进体活性的机制.
主要方法:
- 对p16INK4a促进剂活性进行分析.
- 研究人类双胞胎纤维细胞中Ets1,Ets2和Id1的表达模式.
- 研究Ras-Raf-MEK信号传递和Id1相互作用对p16INK4a诱导的影响.
主要成果:
- 埃特斯1和埃特斯2通过ETS结合部位激活p16INK4a促进体.
- 在年轻的纤维细胞中,Ets2诱导p16INK4a,由Ras-Raf-MEK信号增强,并被Id1.1抑制.
- 在衰老细胞中,减少的Ets2和MEK信号,以及减少的Id1和增加的Ets1,与增加的p16INK4a表达相关.
结论:
- 在细胞衰老过程中,Ets1和Ets2是p16INK4a表达的关键调节者.
- 在Ets转录因子,Id1和Ras-Raf-MEK通路之间的相互作用控制p16INK4a水平和细胞生长停止.
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