Department of Biology, Stanford University, Stanford, CA 94305, USA.
Mol Cell. 2013 Jun 27;50(6):856-68. doi: 10.1016/j.molcel.2013.04.014. Epub 2013 May 16.
Cellular transitions are important for all life. Such transitions, including cell fate decisions, often employ positive feedback regulation to establish and stabilize new cellular states. However, positive feedback is unlikely to underlie stable cell-cycle arrest in yeast exposed to mating pheromone because the signaling pathway is linear, rather than bistable, over a broad range of extracellular pheromone concentration. We show that the stability of the pheromone-arrested state results from coherent feedforward regulation of the cell-cycle inhibitor Far1. This network motif is effectively isolated from the more complex regulatory network in which it is embedded. Fast regulation of Far1 by phosphorylation allows rapid cell-cycle arrest and reentry, whereas slow Far1 synthesis reinforces arrest. We expect coherent feedforward regulation to be frequently implemented at reversible cellular transitions because this network motif can achieve the ostensibly conflicting aims of arrest stability and rapid reversibility without loss of signaling information.
细胞转变对于所有生命都很重要。这种转变，包括细胞命运决定，通常采用正反馈调节来建立和稳定新的细胞状态。然而，由于信号通路在广泛的细胞外激素浓度范围内是线性的，而不是双稳态的，因此在酵母暴露于交配激素时，稳定的细胞周期停滞不太可能依赖于正反馈。我们表明，激素停滞状态的稳定性是由细胞周期抑制剂 Far1 的相干前馈调节产生的。这个网络模块有效地与它所处的更复杂的调节网络隔离开来。Far1 通过磷酸化的快速调节允许快速的细胞周期停滞和重新进入，而缓慢的 Far1 合成则加强了停滞。我们预计，相干前馈调节将经常在可逆的细胞转变中实现，因为这种网络模块可以在不损失信号信息的情况下实现看似矛盾的目标，即停滞稳定性和快速可逆性。
