Sia R A, Herald H A, Lew D J
Department of Molecular Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Mol Biol Cell. 1996 Nov;7(11):1657-66. doi: 10.1091/mbc.7.11.1657.
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 post-translational regulation of Swe1 and that transcriptional feedback loops enhance the efficacy of the checkpoint.
芽殖酵母中的一个形态发生检查点会延迟未形成芽的细胞中的核分裂（以及随后的细胞周期进程）。我们发现，这个检查点延迟核分裂的能力需要SWE1基因，该基因编码一种蛋白激酶，可抑制主要的细胞周期调节激酶Cdc28。在无法形成芽的细胞中，核分裂的时间对SWE1和MIH1基因的剂量极为敏感，这两个基因控制着Cdc28在酪氨酸19位点的磷酸化。相比之下，已出芽细胞中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开启了这一调节途径。我们发现，SWE1 mRNA水平在细胞周期中波动，并且在无法形成芽的细胞中升高。然而，检查点对SWE1 mRNA水平调控是间接的，通过一个需要Swe1活性的反馈环起作用。此外，即使SWE1转录失调，检查点仍能够延迟核分裂。我们提出，检查点通过对Swe1的翻译后调控来延迟核分裂，并且转录反馈环增强了检查点的功效。
