Protein phosphorylation is an essential regulatory mechanism that controls most cellular processes, integrating a variety of environmental signals to drive cellular growth. Isr1 is a negative regulator of the hexosamine biosynthesis pathway (HBP), which produces UDP-GlcNAc, an essential carbohydrate that is the building block of N-glycosylation, GPI anchors and chitin. Isr1 was recently shown to be regulated by phosphorylation by the nutrient-responsive CDK kinase Pho85, allowing it to be targeted for degradation by the SCF^CDC4. Here, we show that while deletion of PHO85 stabilizes Isr1 in asynchronous cells, Isr1 is still unstable in mitotically arrested cells in a pho85∆ strain. We provide evidence to suggest that this is through phosphorylation by CDK1. Redundant targeting of Isr1 by two distinct kinases may allow for tight regulation of the HBP in response to different cellular signals.

蛋白质磷酸化是控制大多数细胞过程的重要调节机制，整合各种环境信号以驱动细胞生长。Isr1 是己糖胺生物合成途径 (HBP) 的负调节剂，它产生 UDP-GlcNAc，这是一种必需的碳水化合物，是N-糖基化、GPI 锚和几丁质的组成部分。最近显示，Isr1 受营养反应性 CDK 激酶 Pho85 磷酸化的调节，使其成为 SCF ^CDC4降解的目标。在这里，我们表明，虽然PHO85的删除稳定了异步细胞中的 Isr1，Isr1 在 pho85Δ 中的有丝分裂停滞细胞中仍然不稳定拉紧。我们提供的证据表明这是通过 CDK1 的磷酸化。两种不同激酶对 Isr1 的冗余靶向可能允许对不同细胞信号的 HBP 进行严格调节。