The Mechanism of Cell Size Regulation

项目摘要 细胞如何调节其大小是一个长期存在的生物学之谜。适当的尺寸调节是 对细胞活力至关重要。细胞大小的失调导致细胞病理学， 与人类疾病，特别是恶性肿瘤有关。然而，人们对此知之甚少。 细胞大小调节机制。我们最近有了一个重要发现， 裂殖酵母细胞大小的调节：有丝分裂的两种直接激活剂，Cdc 13细胞周期蛋白和 Cdc 25磷酸酶以大小依赖性方式表达。这种表达方式是 这是不寻常的，因为大多数蛋白质在细胞生长时保持恒定的浓度。但这 两个关键细胞周期调节因子的异常行为支持了累积激活因子 细胞大小控制假说。积累激活剂假说假定大小- 限制性有丝分裂激活剂的依赖性积累调节细胞大小。的丰度 当细胞很小时，这种激活剂抑制有丝分裂， 激活剂，但当细胞较大并表达大量激活剂时驱动有丝分裂。我们 将直接测试Cdc 25和Cdc 13是在细胞中的冗余积累激活剂的假设。 分裂酵母如果是的话，它将提供第一个经过实验验证的机械模型 来控制生物体的大小即使尺寸控制比 积累Cdc 25和Cdc 13，了解这些大小依赖性积累 两个关键的细胞周期调节剂将提供重要的洞察如何开放的问题， 蛋白质可以以大小依赖性方式表达。因此，我们将对监管进行剖析 Cdc 25的表达，我们已经证明它是受转录调控的， cdc 13，我们已经证明它是转录后调节的。

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.