Feedback control of Swe1p degradation in the yeast morphogenesis checkpoint.
Feedback control of Swe1p degradation in the yeast morphogenesis checkpoint.
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DOI：
10.1091/mbc.e12-11-0812
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发表时间：
2013-04
影响因子：
3.3
通讯作者：
Lew DJ
中科院分区：
文献类型：
--
作者：
King K;Kang H;Jin M;Lew DJ
形态发生检查点稳定有丝分裂抑制剂Swe 1 p，并防止影响芽形成的应力后的有丝分裂。结果表明，在一些应力，Swe 1 p稳定是一个间接的影响细胞周期蛋白依赖性激酶抑制。酿酒酵母细胞暴露于各种生理胁迫下会短暂延迟芽的出现或芽的生长。在这种情况下，为了保持芽形成和细胞周期之间的协调，形态发生检查点通过有丝分裂抑制Wee 1家族激酶Swe 1 p延迟核分裂。Swe 1 p在未应激的细胞中在G2期间降解，但在应激后稳定并积累。Swe 1 p的降解之前，其招聘到隔蛋白支架在母芽颈，介导的Swe 1 p结合蛋白Hsl 7 p。在渗透压休克或肌动蛋白解聚后，Swe 1 p稳定，并且先前的研究表明这是因为Hsl 7 p在应激后不再被募集到隔蛋白支架。然而，我们现在表明Hsl 7 p实际上在应激细胞中被募集到septin支架。使用细胞周期蛋白依赖性激酶（CDK）的突变体，免疫检查点介导的抑制，我们表明，Swe 1 p稳定后的压力是CDK抑制的间接影响。这些发现证明了正反馈回路的生理重要性，其中Swe 1 p活性抑制CDK，然后CDK停止靶向Swe 1 p进行降解。他们还强调了将直接检查点途径与G2/M转换时激活的正反馈循环的影响分开的困难。
The morphogenesis checkpoint stabilizes the mitotic inhibitor Swe1p and prevents mitosis following stresses that affect bud formation. It is shown that, following some stresses, Swe1p stabilization is an indirect effect of cyclin-dependent kinase inhibition. Saccharomyces cerevisiae cells exposed to a variety of physiological stresses transiently delay bud emergence or bud growth. To maintain coordination between bud formation and the cell cycle in such circumstances, the morphogenesis checkpoint delays nuclear division via the mitosis-inhibitory Wee1-family kinase, Swe1p. Swe1p is degraded during G2 in unstressed cells but is stabilized and accumulates following stress. Degradation of Swe1p is preceded by its recruitment to the septin scaffold at the mother-bud neck, mediated by the Swe1p-binding protein Hsl7p. Following osmotic shock or actin depolymerization, Swe1p is stabilized, and previous studies suggested that this was because Hsl7p was no longer recruited to the septin scaffold following stress. However, we now show that Hsl7p is in fact recruited to the septin scaffold in stressed cells. Using a cyclin-dependent kinase (CDK) mutant that is immune to checkpoint-mediated inhibition, we show that Swe1p stabilization following stress is an indirect effect of CDK inhibition. These findings demonstrate the physiological importance of a positive-feedback loop in which Swe1p activity inhibits the CDK, which then ceases to target Swe1p for degradation. They also highlight the difficulty in disentangling direct checkpoint pathways from the effects of positive-feedback loops active at the G2/M transition.