Cdc28 tyrosine phosphorylation and the morphogenesis checkpoint in budding yeast
Cdc28 tyrosine phosphorylation and the morphogenesis checkpoint in budding yeast
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DOI：
10.1091/mbc.7.11.1657
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发表时间：
1996-11-01
影响因子：
3.3
通讯作者：
Lew, DJ
中科院分区：
文献类型：
--
作者：
Sia, RAL;Herald, HA;Lew, DJ
发芽酵母中的形态发生检查点推迟了未能形成芽的细胞的核分裂(以及随后的细胞周期进展)。我们证明，这个检查点推迟核分裂的能力需要SWE1基因，它编码一种蛋白激酶，抑制主细胞周期调节激酶CDc28。在不能形成花蕾的细胞中，核分裂的时间对SWE1和MIH1基因的剂量非常敏感，这两个基因控制着CDc28在酪氨酸19的磷酸化。相反，出芽细胞的核分裂时间并不依赖于CDc28的磷酸化，这表明形态发生检查点以某种方式启动了这一调节途径。我们发现，SWE1的mRNA水平在细胞周期中波动，并在不能形成芽的细胞中升高。然而，检查点对SWE1 mRNA水平的调节是间接的，通过需要Swe1活性的反馈环起作用。此外，即使在SWE1转录被解除调控的情况下，检查点也能够延迟核分裂。我们认为，检查点通过对Swe1的翻译后调节来推迟核分裂，并且转录反馈环增强了检查点的效率。
A morphogenesis checkpoint in budding yeast delays nuclear division (and subsequent cell cycle progression) in cells that have failed to make a bud. We show that the ability of this checkpoint to delay nuclear division requires the SWE1 gene, encoding a protein kinase that inhibits the master cell cycle regulatory kinase Cdc28. The timing of nuclear division in cells that cannot make a bud is exquisitely sensitive to the dosage of SWE1 and MIH1 genes, which control phosphorylation of Cdc28 at tyrosine 19. In contrast, the timing of nuclear division in budded cells does not rely on Cdc28 phosphorylation, suggesting that the morphogenesis checkpoint somehow turns on this regulatory pathway. We show that SWE1 mRNA levels fluctuate during the cell cycle and are elevated in cells that cannot make a bud. However, regulation of SWE1 mRNA levels by the checkpoint is indirect, acting through a feedback loop requiring Swe1 activity. Further, the checkpoint is capable of delaying nuclear division even when SWE1 transcription is deregulated. We propose that the checkpoint delays nuclear division through posttranslational regulation of Swe1 and that transcriptional feedback loops enhance the efficacy of the checkpoint.