The Mechanism of Cell Size Regulation

项目总结 细胞如何调节自己的大小是一个长期存在的生物学谜团。适当的大小调节是 对细胞存活至关重要。细胞大小的失调会导致细胞病理和IS 与人类疾病，特别是恶性肿瘤有关。然而，人们对这一事件知之甚少 细胞大小调节的机制。我们最近有了一个重要的发现， 分裂酵母中的细胞大小调节：有丝分裂的两个直接激活剂，即CDC13细胞周期蛋白和 CDC25磷酸酶以一种大小依赖的方式表达。这种表达方式是 不同寻常，因为大多数蛋白质在细胞生长过程中保持恒定的浓度。不过，这个 两个关键的细胞周期调节因子的异常行为支持蓄积激活剂 细胞大小控制假说。累积激活剂假说假设大小-- 限制性有丝分裂激活剂的依赖积累调节细胞大小。丰富的…… 当细胞很小时，这种激活剂抑制有丝分裂，并表达少量的 激活剂，但驱动有丝分裂时，细胞较大，并表达大量的激活剂。我们 将直接测试CDC25和CDC13是多余的累积激活剂的假设 裂变型酵母。如果是这样的话，它将提供第一个经过实验验证的机械模型 用来控制任何生物体的大小。即使大小控制比 CDC25和CDC13的积累，了解这些物质的大小依赖积累 两个关键的细胞周期调节因子将为如何解决这一悬而未决的问题提供重要的见解 蛋白质可以以大小依赖的方式表达。因此，我们将对这一规定进行剖析 CDC25的表达，我们已经证明它是受转录调控的，以及 CDC13，我们已经证明它是转录后调控的。

PROJECT SUMMARY How cells regulate their size is an long-standing biological mystery. Proper size regulation is essential for cell viability. Dysregulation of cell size leads to cellular pathology and is associated with human disease, particular malignancies. Yet, little is know about the mechanisms of cell size regulation. We have recently made a important discovery regarding cell size regulation in fission yeast: two direct activators of mitosis, the Cdc13 cyclin and the Cdc25 phosphatase, are expressed in a size-dependent manner. This manner of expression is unusual because most proteins maintain a constant concentration as cells grow. However, this unusual behavior of two key cell cycle regulators supports the accumulating-activator hypothesis of cell size control. The accumulating-activator hypothesis posits that size- dependent accumulation of a limiting mitotic activator regulates cell size. The abundance of such an activator restrains mitosis when cells are small and express low amounts of the activator, but drives mitosis when cells are large and express high amounts of the activator. We will directly test the hypothesis that Cdc25 and Cdc13 are redundant accumulating activators in fission yeast. If they are, it will provide the first experimentally validated, mechanistic model for size control in any organism. Even if size control is more complicated than just the accumulation of Cdc25 and Cdc13, understanding the size-dependent accumulation of these two key cell cycle regulators will provide important insight into the open question of how proteins can be expressed in a size dependent manner. Therefore, we will dissect the regulation of expression of both Cdc25, which we have shown to be regulated transcriptionally, and Cdc13, which we have shown to be regulated post-transcriptionally.