Glucose inhibits meiotic DNA replication through SCFGrr1p-dependent destruction of Ime2p kinase.
Glucose inhibits meiotic DNA replication through SCFGrr1p-dependent destruction of Ime2p kinase.
复制标题
葡萄糖通过 Ime2p 激酶的 SCFGrr1p 依赖性破坏来抑制减数分裂 DNA 复制。
DOI：
10.1128/mcb.25.1.440-450.2005
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发表时间：
2005
影响因子：
5.3
通讯作者：
Honigberg,SaulM
中科院分区：
文献类型：
--
作者：
Purnapatre,Kedar;Gray,Misa;Piccirillo,Sarah;Honigberg,SaulM
在芽殖酵母酿酒酵母中，细胞分裂周期和孢子形成是相互排斥的细胞命运;刺激细胞分裂周期的葡萄糖是孢子形成的有效抑制剂。在孢子形成培养基中添加中等浓度的葡萄糖（0.5%）并不抑制孢子形成的两个关键激活因子IME 1和IME 2的转录，但确实增加了Sic 1 p（一种细胞周期蛋白依赖性激酶抑制剂）的水平，导致减数分裂DNA复制的阻断。葡萄糖对Sic 1 p水平和DNA复制的影响需要Grr 1 p，这是SCFGrr 1泛素连接酶的一个组成部分。Sic 1 p受Ime 2 p激酶负调控，一些观察结果表明，葡萄糖通过SCFGrr 1 p介导的该激酶的破坏抑制减数分裂DNA复制。首先，Ime 2 p在葡萄糖存在下不稳定，这种周转需要Grr 1 p，SCFGrr 1 p的第二个组分Cdc 53 p和SCFGrr 1 p相关的E2酶Cdc 34 p。其次，在Ime 2 p快速周转的条件下检测Ime 2 p-泛素缀合物，并且Ime 2 p与泛素的缀合需要GRR 1。第三，Ime 2 p的突变形式（Ime 2 ΔPEST），其中一个假定的Grr 1 p相互作用序列被删除，比野生型Ime 2 p更稳定。最后，IME 2 Δ PEST等位基因的表达绕过了0.5%葡萄糖对减数分裂DNA复制的阻断。此外，Grr 1 p是需要在孢子形成独立的Ime 2 p营业额的作用，后来的事件。
In the budding yeastSaccharomyces cerevisiae, the cell division cycle and sporulation are mutually exclusive cell fates; glucose, which stimulates the cell division cycle, is a potent inhibitor of sporulation. Addition of moderate concentrations of glucose (0.5%) to sporulation medium did not inhibit transcription of two key activators of sporulation,IME1andIME2,but did increase levels of Sic1p, a cyclin-dependent kinase inhibitor, resulting in a block to meiotic DNA replication. The effects of glucose on Sic1p levels and DNA replication required Grr1p, a component of the SCFGrr1pubiquitin ligase. Sic1p is negatively regulated by Ime2p kinase, and several observations indicate that glucose inhibits meiotic DNA replication through SCFGrr1p-mediated destruction of this kinase. First, Ime2p was destabilized in the presence of glucose, and this turnover required Grr1p, a second component of SCFGrr1p, Cdc53p, and an SCFGrr1p-associated E2 enzyme, Cdc34p. Second, Ime2p-ubiquitin conjugates were detected under conditions of rapid Ime2p turnover, and conjugation of Ime2p to ubiquitin requiredGRR1. Third, a mutant form of Ime2p (Ime2ΔPEST), in which a putative Grr1p-interacting sequence was deleted, was more stable than wild-type Ime2p. Finally, expression of theIME2ΔPESTallele bypassed the block to meiotic DNA replication caused by 0.5% glucose. In addition, Grr1p is required for later events in sporulation independently of its role in Ime2p turnover.