首页> 外文学位 >Regulation of meiotic development in Saccharomyces cerevisiae by the meiosis-specific Ime2 protein kinase.
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Regulation of meiotic development in Saccharomyces cerevisiae by the meiosis-specific Ime2 protein kinase.

机译:减数分裂特异性Ime2蛋白激酶对酿酒酵母减数分裂发育的调控。

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摘要

Meiosis is the evolutionarily conserved process by which sexually reproducing organisms generate haploid gametes. In the yeast, Saccharomyces cerevisiaie, meiosis is linked to the formation of spores. As in mitosis, meiosis is driven by the cyclin-dependent kinase (CDK), Cdk1. Additionally, Ime2, a meiosis-specific CDK-like kinase, superimposes meiosis-specific regulation on the cell cycle machinery that is shared between mitosis and meiosis. Here, I define the Ime2 phosphorylation consensus motif to be R-P-X-S/T-A, which is distinct from Cdk1 (S/T-P). The Ime2 consensus motif has predictive value in identifying novel substrates. Cdc20 is substrate targeting subunit of the Anaphase Promoting Complex (APC/C) that triggers chromosome segregation. I show that Ime2 inhibits Cdc20 through a single phospho-acceptor site that is adjacent to an APC/C binding motif. In addition to protein kinase signaling, the sporulation program is tightly controlled by a transcriptional cascade. The commitment point, after which the inducing signal is no longer necessary for completion of the program, is at the end of premeiotic prophase just before the cells execute the first meiotic division. This transition requires the induction of Middle Sporulation Genes (MSGs). The Sum1 repressor inhibits MSG expression while the Ndt80 transcription factor is the principal inducer of MSGs. NDT80 is itself controlled by a tightly regulated MSG promoter in a positive autoregulatory loop. Sum1 represses the NDT80 promoter in vegetative cells and early prophase. I show that Ime2 and Cdk1 negatively regulate Sum1. Phosphorylation of Sum1, specifically at the NDT80 promoter, derepresses NDT80. This allows the NDT80 autoregulatory loop to proceed, leading to MSG induction and commitment to meiosis. Genetic evidence indicates one mechanism used by Ime2 and Cdk1 to trigger NDT80 is inhibition of Rfm1/Hst1, a histone deacetylase complex known to bind Sum1. In this mechanism, Ime2 works with Cdk1 to exert meiosis-specific control over MSG expression and meiotic commitment. This work suggests a paradigm by which CDK and cell-type specific CDK-like kinases co-regulate commitment to a cellular differentiation program by regulating a transcriptional cascade.
机译:减数分裂是有性繁殖生物产生单倍体配子的进化保守过程。在酵母中,减数分裂与孢子的形成有关。与有丝分裂一样,减数分裂由细胞周期蛋白依赖性激酶(CDK)Cdk1驱动。此外,Ime2是一种减数分裂特有的CDK样激酶,可将减数分裂特有的调节作用叠加在有丝分裂和减数分裂之间共享的细胞周期机制上。在这里,我将Ime2磷酸化共有基序定义为R-P-X-S / T-A,这与Cdk1(S / T-P)不同。 Ime2共有主题在识别新型底物方面具有预测价值。 Cdc20是触发染色体分离的后期促进复合体(APC / C)的底物靶向亚基。我表明,Ime2通过与APC / C结合基序相邻的单个磷酸受体位点抑制Cdc20。除了蛋白激酶信号传导外,孢子形成程序还受转录级联的严格控制。承诺点,在该承诺点之后,不再需要信号来完成程序,恰好在细胞执行第一次减数分裂之前,在减数分裂前期结束时。这种转变需要诱导中孢子基因(MSG)。 Sum1阻遏物抑制MSG表达,而Ndt80转录因子是MSG的主要诱导物。 NDT80本身由正调控的MSG启动子严格调控。 Sum1抑制营养细胞和早期阶段的NDT80启动子。我表明Ime2和Cdk1负调节Sum1。 Sum1的磷酸化,特别是在NDT80启动子处,会抑制NDT80。这使NDT80自动调节循环得以进行,从而导致MSG诱导并致力于减数分裂。遗传证据表明,Ime2和Cdk1用来触发NDT80的一种机制是抑制Rfm1 / Hst1,Rfm1 / Hst1是一种已知与Sum1结合的组蛋白脱乙酰基酶复合物。在这种机制中,Ime2与Cdk1一起对MSG表达和减数分裂承诺进行减数分裂特异性控制。这项工作提出了一种范式,通过该范式,CDK和特定于细胞类型的CDK样激酶通过调节转录级联反应共同调节对细胞分化程序的承诺。

著录项

  • 作者

    Shin, Marcus.;

  • 作者单位

    Thomas Jefferson University.;

  • 授予单位 Thomas Jefferson University.;
  • 学科 Biology Molecular.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 160 p.
  • 总页数 160
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 财务管理、经济核算;
  • 关键词

  • 入库时间 2022-08-17 11:36:54

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