Abstract：
Decades ago, mitogen-promoted signaling duration and strength were observed to be sensed by the cell and to be critical for its decisions: to proliferate or differentiate. Landmark publications established the importance of mitogen signaling not only in the G1 cell cycle phase but also through the S and the G2/M transition. Despite these early milestones, how mitogen signal duration and strength, short and strong or weaker and sustained, control cell fate has been largely unheeded. Here, we center on cardinal signaling-related questions, including (i) how fluctuating mitogenic signals are converted into cell proliferation-differentiation decisions and (ii) why extended duration of weak signaling is associated with differentiation, while bursts of strong and short induce proliferation but, if too strong and long, induce irreversible senescence. Our innovative broad outlook harnesses cell biology and protein conformational ensembles, helping us to define signaling strength, clarify cell cycle decisions, and thus cell fate.
摘要：
几十年前,观察到有丝分裂原促进的信号传导持续时间和强度被细胞感知，并且对于其决定：增殖或分化至关重要。具有里程碑意义的出版物不仅在G1细胞周期阶段而且在S和G2/M过渡中确立了丝裂原信号传导的重要性。尽管有这些早期的里程碑，丝裂原信号的持续时间和强度，短而强，弱而持续，控制细胞的命运在很大程度上没有受到重视。这里,我们以基本信号相关的问题为中心，包括（i）波动的有丝分裂信号如何转化为细胞增殖-分化决定，以及（ii）为什么延长的弱信号持续时间与分化有关，虽然强和短的爆发诱导增殖，但是，如果太强大和漫长，诱导不可逆衰老。我们创新的广阔前景利用细胞生物学和蛋白质构象集合，帮助我们定义信号强度，阐明细胞周期决定，从而细胞命运。
