Eukaryotic Cell Cycle Control

细胞周期控制是最复杂的细胞调控系统之一，它决定了细胞在外界条件下增殖、停滞和分化的时间和进程。我们的目标是了解这个监管体系的整体轮廓。为此，我们一直在研究啮齿动物成纤维细胞和裂变酵母作为模式生物。在这一学期中，我们取得了以下进展。我们已经分离出两个控制细胞周期和分化的新因子。一个是新的周期蛋白，另一个是控制b型周期蛋白降解的WD重复蛋白。我们已经确定了两个对姐妹染色单体内聚的建立和维持至关重要的新因素。一个是与polη融合的蛋白质，这是复制后修复所必需的，另一个是姐妹染色单体内聚的稳定性和抑制不需要的染色单体内聚所必需的因子。Cdk6-D3复合物在其他D周期蛋白激酶组合中能够逃避ckl的抑制并控制细胞的生长能力。致癌刺激在细胞周期开始的关键步骤中招募Cdk6，其机制似乎与调节其活性或亚细胞定位无关。考虑到造血细胞主要使用Cdk6启动细胞周期并进行非锚定生长，这一发现提出了一种可能性，即由致癌转化诱导的非锚定细胞周期启动是由一种类似于造血细胞增殖的机制引发的。我们已经分离出一种裂变酵母分化调控的人类同源物。正如预期的那样，该基因的过表达阻断了人类白血病细胞的核细胞和红细胞分化。

Cell cycle control is one of the most complicated cellular regulatory systems and determined the timing and progression of cell proliferation, arrest and differentiation in response to external conditions. Our goal is to understand the entire outline of this regulatory system. To this end, we have been studying rodent fibroblasts and fission yeast as model organisms. In this term, we have mode the following progresses.1. We have isolated two novel factors that control the cell cycle and differentiation stars. One is a new cyclin and the other a WD repeat protein that controls degradation of B-type cyclin.2. We have identified two new factors that are essential for the establishment and maintenance of sister chromatid cohesion. One is a protein fused with polη that is required for post-replication repair, and the other a factor required for stability of sister chromatid cohesion and for inhibition of undesired chromatid cohesion.3. Cdk6-D3 complex among the other D cyclin- kinase combinations is able to evade inhibition by CKls and to control cell's growth competence.4. Oncogenic stimulation recruits Cdk6 in a critical step of the cell cycle start, via a mechanism seemingly unrelated to the regulation of its activity or subcellular localization. Given that hematopoietic cells employ predominantly Cdk6 for the cell cycle start and perform anchorage-independent growth by nature, this finding raises the possibility that the anchorage-independent cell cycle start induced by oncogenic transformation is elicited by a mechanism similar to the one employed for hematopoietic cell proliferation.5. We have isolated a human homologue of a fission yeast differentiation regulation. As anticipated, overexpression of this gene blocks magakaryotic and erythroid differentiation of a human leukemia cell.