Sia R A, Bardes E S, Lew D J
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
EMBO J. 1998 Nov 16;17(22):6678-88. doi: 10.1093/emboj/17.22.6678.
In the budding yeast Saccharomyces cerevisiae, a cell cycle checkpoint coordinates mitosis with bud formation. Perturbations that transiently depolarize the actin cytoskeleton cause delays in bud formation, and a 'morphogenesis checkpoint' detects the actin perturbation and imposes a G2 delay through inhibition of the cyclin-dependent kinase, Cdc28p. The tyrosine kinase Swe1p, homologous to wee1 in fission yeast, is required for the checkpoint-mediated G2 delay. In this report, we show that Swe1p stability is regulated both during the normal cell cycle and in response to the checkpoint. Swe1p is stable during G1 and accumulates to a peak at the end of S phase or in early G2, when it becomes unstable and is degraded rapidly. Destabilization of Swe1p in G2 and M phase depends on the activity of Cdc28p in complexes with B-type cyclins. Several different perturbations of actin organization all prevent Swe1p degradation, leading to the persistence or further accumulation of Swe1p, and cell cycle delay in G2.
在出芽酵母酿酒酵母中，一个细胞周期检查点将有丝分裂与芽的形成协调起来。使肌动蛋白细胞骨架瞬时去极化的干扰会导致芽形成延迟，一个“形态发生检查点”会检测到肌动蛋白的干扰，并通过抑制细胞周期蛋白依赖性激酶Cdc28p来造成G2期延迟。酪氨酸激酶Swe1p与裂殖酵母中的wee1同源，是检查点介导的G2期延迟所必需的。在本报告中，我们表明Swe1p的稳定性在正常细胞周期中以及对检查点的反应中均受到调控。Swe1p在G1期稳定，并在S期末或G2早期积累至峰值，此时它变得不稳定并迅速降解。Swe1p在G2期和M期的不稳定取决于Cdc28p与B型细胞周期蛋白形成的复合物的活性。肌动蛋白组织的几种不同干扰均会阻止Swe1p降解，导致Swe1p持续存在或进一步积累，并使细胞周期在G2期延迟。
