Ribosome biogenesis is sensed at the start cell cycle checkpoint
Ribosome biogenesis is sensed at the start cell cycle checkpoint
复制标题
DOI：
10.1091/mbc.e06-06-0512
复制
发表时间：
2007-03-01
影响因子：
3.3
通讯作者：
Baserga, Susan J.
中科院分区：
文献类型：
--
作者：
Bernstein, Kara A.;Bleichert, Franziska;Baserga, Susan J.
在酿酒酵母中，人们一直认为细胞必须达到一个临界的细胞大小，即所谓的“设定点”，才能开始细胞周期的转变。最近的证据表明，当核糖体生物发生放缓时，这一设定点会降低。在这里，我们提出的证据表明，酵母可以独立于成熟的核糖体水平和蛋白质合成能力来感知核糖体的生物发生。我们的结果表明，核糖体的生物发生直接促进START通过Whi5，Whi5是酵母功能相当于人类肿瘤抑制因子Rb。当核糖体生物发生被抑制时，依赖于Whi5的机制在核糖体数量和细胞总翻译能力明显下降之前抑制通过START。这种对核糖体生物发生减少的反应在开始时的延迟独立于已知的主要Whi5拮抗剂Cln3。因此，核糖体的生物发生可以在START调节的多个步骤中被感觉到。因此，核糖体生物发生既可以通过增加细胞大小设定点来推迟启动，也可以独立地通过灭活WHI5来促进启动。
In the yeast Saccharomyces cerevisiae it has long been thought that cells must reach a critical cell size, called the "setpoint," in order to allow the Start cell cycle transition. Recent evidence suggests that this setpoint is lowered when ribosome biogenesis is slowed. Here we present evidence that yeast can sense ribosome biogenesis independently of mature ribosome levels and protein synthetic capacity. Our results suggest that ribosome biogenesis directly promotes passage through Start through Whi5, the yeast functional equivalent to the human tumor suppressor Rb. When ribosome biogenesis is inhibited, a Whi5-dependent mechanism inhibits passage through Start before significant decreases in both the number of ribosomes and in overall translation capacity of the cell become evident. This delay at Start in response to decreases in ribosome biogenesis occurs independently of Cln3, the major known Whi5 antagonist. Thus ribosome biogenesis may be sensed at multiple steps in Start regulation. Ribosome biogenesis may thus both delay Start by increasing the cell size setpoint and independently may promote Start by inactivating Whi5.