Abstract：
Starvation in diploid budding yeast cells triggers a cell-fate program culminating in meiosis and spore formation. Transcriptional activation of early meiotic genes (EMGs) hinges on the master regulator Ime1, its DNA-binding partner Ume6, and GSK-3β kinase Rim11. Phosphorylation of Ume6 by Rim11 is required for EMG activation. We report here that Rim11 functions as the central signal integrator for controlling Ume6 phosphorylation and EMG transcription. In nutrient-rich conditions, PKA suppresses Rim11 levels, while TORC1 retains Rim11 in the cytoplasm. Inhibition of PKA and TORC1 induces Rim11 expression and nuclear localization. Remarkably, nuclear Rim11 is required, but not sufficient, for Rim11-dependent Ume6 phosphorylation. In addition, Ime1 is an anchor protein enabling Ume6 phosphorylation by Rim11. Subsequently, Ume6-Ime1 coactivator complexes form and induce EMG transcription. Our results demonstrate how various signaling inputs (PKA/TORC1/Ime1) converge through Rim11 to regulate EMG expression and meiosis initiation. We posit that the signaling-regulatory network elucidated here generates robustness in cell-fate control.
摘要：
二倍体出芽酵母细胞的饥饿会触发细胞命运程序，最终导致减数分裂和孢子形成。早期减数分裂基因（EMGs）的转录激活取决于主调节因子Ime1，其DNA结合伴侣Ume6和GSK-3β激酶Rim11。EMG活化需要Rim11对Ume6的磷酸化。我们在这里报道Rim11充当控制Ume6磷酸化和EMG转录的中心信号整合者。在营养丰富的条件下，PKA抑制Rim11水平,而TORC1将Rim11保留在细胞质中。抑制PKA和TORC1诱导Rim11表达和核定位。值得注意的是,核Rim11是必需的，但还不够,Rim11依赖性Ume6磷酸化。此外,Ime1是通过Rim11使Ume6磷酸化的锚定蛋白。随后，Ume6-Ime1共激活因子复合物形成并诱导EMG转录。我们的结果表明各种信号输入（PKA/TORC1/Ime1）如何通过Rim11会聚以调节EMG表达和减数分裂起始。我们认为，这里阐明的信号调节网络在细胞命运控制中产生了鲁棒性。
