A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle.
A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle.
复制标题
DOI：
10.1073/pnas.2206172119
复制
发表时间：
2022-09-06
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
在真核生物中，细胞周期蛋白依赖性激酶（CDK）活性水平的增加推动了细胞周期的进展。由于大多数细胞以特定的大小分裂，因此响应细胞大小的信息必须输入CDK活性的调节。在这项研究中，我们使用裂殖酵母来精确测量先前在全基因组筛选中被鉴定为细胞周期调节因子的蛋白质如何随着细胞周期进程而改变其水平。我们确定有丝分裂B型细胞周期蛋白Cdc13和有丝分裂抑制性磷酸酶Cdc25作为唯一的两种蛋白质，通过细胞周期的变化，在整个细胞和核浓度，使其成为潜在的候选人，在有丝分裂和细胞分裂的发病通用细胞大小传感器。我们已经进行了系统水平的空间和时间动态的细胞周期调节因子在裂殖酵母裂殖酵母粟酒裂殖酵母。在一个全面的单细胞分析中，我们精确地定量了38种蛋白质的水平，这些蛋白质先前被确定为G2到有丝分裂过渡的调节因子，7种蛋白质作用于G1到S期过渡。38个有丝分裂调节剂中只有2个在全细胞水平上表现出浓度变化：有丝分裂B型细胞周期蛋白Cdc13，其在整个细胞周期中不断积累，以及调节磷酸酶Cdc25，其表现出复杂的细胞周期模式。这两种蛋白质在细胞核内显示出与整个细胞相似的变化模式，但浓度更高。此外，主要分裂酵母细胞周期蛋白依赖性激酶（CDK）Cdc2，CDK调节Suc1和抑制性激酶Wee1的浓度也在细胞核中增加，在有丝分裂开始时达到峰值，但在整个细胞中是恒定的。Cdc13浓度随细胞大小的显著增加支持了有丝分裂B型细胞周期蛋白积累可以作为细胞大小传感器的观点。我们提出了一个两步控制有丝分裂的过程。首先，Cdc 13以尺寸依赖性方式积累，从而驱动CDK活性增加。第二，从中期G2，增加Cdc25和抵消Wee1的核积累引入双稳态开关，导致在G2结束时CDK活性的快速上升，从而导致有序的有丝分裂。
Across eukaryotes, the increasing level of cyclin-dependent kinase (CDK) activity drives progression through the cell cycle. As most cells divide at specific sizes, information responding to the size of the cell must feed into the regulation of CDK activity. In this study, we use fission yeast to precisely measure how proteins that have been previously identified in genome-wide screens as cell cycle regulators change in their levels with cell cycle progression. We identify the mitotic B-type cyclin Cdc13 and the mitotic inhibitory phosphatase Cdc25 as the only two proteins that change in both whole-cell and nuclear concentration through the cell cycle, making them potential candidates for universal cell size sensors at the onset of mitosis and cell division. We have carried out a systems-level analysis of the spatial and temporal dynamics of cell cycle regulators in the fission yeast Schizosaccharomyces pombe. In a comprehensive single-cell analysis, we have precisely quantified the levels of 38 proteins previously identified as regulators of the G2 to mitosis transition and of 7 proteins acting at the G1- to S-phase transition. Only 2 of the 38 mitotic regulators exhibit changes in concentration at the whole-cell level: the mitotic B-type cyclin Cdc13, which accumulates continually throughout the cell cycle, and the regulatory phosphatase Cdc25, which exhibits a complex cell cycle pattern. Both proteins show similar patterns of change within the nucleus as in the whole cell but at higher concentrations. In addition, the concentrations of the major fission yeast cyclin-dependent kinase (CDK) Cdc2, the CDK regulator Suc1, and the inhibitory kinase Wee1 also increase in the nucleus, peaking at mitotic onset, but are constant in the whole cell. The significant increase in concentration with size for Cdc13 supports the view that mitotic B-type cyclin accumulation could act as a cell size sensor. We propose a two-step process for the control of mitosis. First, Cdc13 accumulates in a size-dependent manner, which drives increasing CDK activity. Second, from mid-G2, the increasing nuclear accumulation of Cdc25 and the counteracting Wee1 introduce a bistability switch that results in a rapid rise of CDK activity at the end of G2 and thus, brings about an orderly progression into mitosis.
登录
查看更多内容
DOI：
10.1126/science.1245075
发表时间：
2015-05-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ginzberg MB;Kafri R;Kirschner M
通讯作者：
Kirschner M
影响因子：
16
作者：
Araujo, Ana Rita;Gelens, Lendert;Sheriff, Rahuman S. M.;Santos, Silvia D. M.
通讯作者：
Santos, Silvia D. M.
影响因子：
21.3
作者：
Jackman, M;Lindon, C;Pines, J
通讯作者：
Pines, J
影响因子：
16
作者：
Kamenz, Julia;Mihaljev, Tamara;Hauf, Silke
通讯作者：
Hauf, Silke
影响因子：
5.8
作者：
Hayles J;Wood V;Jeffery L;Hoe KL;Kim DU;Park HO;Salas-Pino S;Heichinger C;Nurse P
通讯作者：
Nurse P