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Polar gradients of the DYRK-family kinase Pom1 couple cell length with the cell cycle

机译：DYRK家族激酶Pom1的极性梯度将细胞长度与细胞周期联系起来

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摘要

Cells normally grow to a certain size before they enter mitosis and divide. Entry into mitosis depends on the activity of Cdk1, which is inhibited by the Wee1 kinase and activated by the Cdc25 phospha-tase. However, how cells sense their size for mitotic commitment remains unknown. Here we show that an intracellular gradient of the dual-specificity tyrosine-phosphorylation regulated kinase (DYRK) Pom1, which emanates from the ends of rod-shaped Schizosaccharomyces potnbe cells, serves to measure cell length and control mitotic entry. Pom1 provides positional information both for polarized growth and to inhibit cell division at cell ends. We discovered that Pom1 is also a dose-dependent G2-M inhibitor. Genetic analyses indicate that Pom1 negatively regulates Cdr1 and Cdr2, two previously described Wee1 inhibitors of the SAD kinase family. This inhibition may be direct, because in vivo and in vitro evidence suggest that Pom1 phosphorylates Cdr2. Whereas Cdrl and Cdr2 localize to a medial cortical region, Pom1 forms concentration gradients from cell tips that overlap with Cdrl and Cdr2 in short cells, but not in long cells. Disturbing these Pom1 gradients leads to Cdr2 phosphorylation and imposes a G2 delay. In short cells, Pom1 prevents precocious M-phase entry, suggesting that the higher medial Pom1 levels inhibit Cdr2 and promote a G2 delay. Thus, gradients of Pom1 from cell ends provide a measure of cell length to regulate M-phase entry.
机译：细胞通常在进入有丝分裂并分裂之前会生长到一定大小。进入有丝分裂取决于Cdk1的活性，其受Wee1激酶抑制并被Cdc25磷酸酶激活。然而，细胞如何感觉到其有丝分裂承诺的大小仍然未知。在这里，我们显示了双特异性酪氨酸磷酸化调节的激酶（DYRK）Pom1的细胞内梯度，它从杆状Schizosaccharomyces potnbe细胞的末端发出，用于测量细胞长度和控制有丝分裂进入。 Pom1提供极化生长和抑制细胞末端细胞分裂的位置信息。我们发现Pom1还是剂量依赖性G2-M抑制剂。遗传分析表明，Pom1负调节Cdr1和Cdr2，这是先前描述的SAD激酶家族的Wee1抑制剂。这种抑制作用可能是直接的，因为体内和体外的证据表明Pom1使Cdr2磷酸化。尽管Cdr1和Cdr2定位在内侧皮层区域，但Pom1在短细胞中形成了与Cdrl和Cdr2重叠的细胞尖端的浓度梯度，而在长细胞中则没有。干扰这些Pom1梯度会导致Cdr2磷酸化并施加G2延迟。在短细胞中，Pom1阻止早熟M期进入，这表明较高的Pom1内侧水平抑制Cdr2并促进G2延迟。因此，来自细胞末端的Pom1梯度可提供细胞长度的量度，以调节M期进入。

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  • 来源
    《Nature》 |2009年第7248期|852-856|共5页
  • 作者

    Sophie G. Martin; Martine Berthelot-Grosjean;

  • 作者单位

    Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Genopode Building, 1015 Lausanne, Switzerland;

    Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Genopode Building, 1015 Lausanne, Switzerland;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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