A positive-feedback-based bistable 'memory module' that governs a cell fate decision
A positive-feedback-based bistable 'memory module' that governs a cell fate decision
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DOI：
10.1038/nature02089
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发表时间：
2003-11-27
期刊：
影响因子：
64.8
通讯作者：
Ferrell, JE
中科院分区：
文献类型：
--
作者：
Xiong, W;Ferrell, JE
非洲爪蟾卵母细胞的成熟可被视为一个细胞命运诱导的过程，未成熟的卵母细胞代表默认命运，而成熟的卵母细胞代表诱导命运（1,2）。已知非洲爪蟾卵母细胞成熟的关键介质，包括p42丝裂原活化蛋白激酶（MAPK）和细胞分裂周期蛋白激酶Cdc2，被组织成正反馈回路（3）。原则上，这种正反馈回路可以对瞬时诱导刺激产生一种主动维持的“记忆”，并可以解释成熟的不可逆性（3 - 6）。在此我们表明，p42 MAPK和Cdc2系统通常会从瞬时刺激产生不可逆的生化反应，但当正反馈被阻断时，该反应变为瞬时的。我们的结果解释了一组内在可逆的信号转导分子如何在系统水平上产生不可逆的反应，并展示了细胞命运如何通过蛋白激酶激活的自我维持模式得以维持。
The maturation of Xenopus oocytes can be thought of as a process of cell fate induction, with the immature oocyte representing the default fate and the mature oocyte representing the induced fate(1,2). Crucial mediators of Xenopus oocyte maturation, including the p42 mitogen-activated protein kinase (MAPK) and the cell-division cycle protein kinase Cdc2, are known to be organized into positive feedback loops(3). In principle, such positive feedback loops could produce an actively maintained 'memory' of a transient inductive stimulus and could explain the irreversibility of maturation(3-6). Here we show that the p42 MAPK and Cdc2 system normally generates an irreversible biochemical response from a transient stimulus, but the response becomes transient when positive feedback is blocked. Our results explain how a group of intrinsically reversible signal transducers can generate an irreversible response at a systems level, and show how a cell fate can be maintained by a self-sustaining pattern of protein kinase activation.