Division of Stem Cell Biology and Developmental Genetics, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, England, UK.
J Cell Biol. 2010 Dec 13;191(6):1097-112. doi: 10.1083/jcb.201005070.
Lte1 is known as a regulator of mitotic progression in budding yeast. Here we demonstrate phosphorylation-dependent inhibition of polarized bud growth during G2/M by Lte1. Cla4 activity first localizes Lte1 to the polarity cap and thus specifically to the bud. This localization is a prerequisite for subsequent Clb-Cdk-dependent phosphorylation of Lte1 and its relocalization to the entire bud cortex. There, Lte1 interferes with activation of the small GTPases, Ras and Bud1. The inhibition of Bud1 prevents untimely polarization until mitosis is completed and Cdc14 phosphatase is released. Inhibition of Bud1 and Ras depends on Lte1's GEF-like domain, which unexpectedly inhibits these small G proteins. Thus, Lte1 has dual functions for regulation of mitotic progression: it both induces mitotic exit and prevents polarized growth during mitotic arrest, thereby coupling cell cycle progression and morphological development.
Lte1 是芽殖酵母有丝分裂进程的调节因子。在这里，我们证明了 Lte1 在 G2/M 期通过磷酸化依赖性抑制极性芽生长。Cla4 活性首先将 Lte1 定位到极性帽，从而特异性地定位到芽。这种定位是 Lte1 随后被 Clb-Cdk 依赖性磷酸化和重新定位到整个芽皮质所必需的。在那里，Lte1 干扰小 GTPases Ras 和 Bud1 的激活。抑制 Bud1 可以防止过早极化，直到有丝分裂完成并释放 Cdc14 磷酸酶。抑制 Bud1 和 Ras 依赖于 Lte1 的 GEF 样结构域，该结构域出人意料地抑制这些小 G 蛋白。因此，Lte1 具有调节有丝分裂进程的双重功能：它既能诱导有丝分裂退出，又能防止有丝分裂停滞期间的极化生长，从而将细胞周期进程和形态发育联系起来。
