Department of Biological Science, Faculty of Science, Shizuoka University, Shizuoka 422-8021, Japan.
Course of Biological Science, Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka 422-8021, Japan.
J Mol Biol. 2018 May 25;430(11):1671-1684. doi: 10.1016/j.jmb.2018.04.007. Epub 2018 Apr 22.
Cdc14 protein phosphatase is critical for late mitosis progression in budding yeast, although its orthologs in other organisms, including mammalian cells, function as stress-responsive phosphatases. We found herein unexpected roles of Cdc14 in autophagy induction after nutrient starvation and target of rapamycin complex 1 (TORC1) kinase inactivation. TORC1 kinase phosphorylates Atg13 to repress autophagy under nutrient-rich conditions, but if TORC1 becomes inactive upon nutrient starvation or rapamycin treatment, Atg13 is rapidly dephosphorylated and autophagy is induced. Cdc14 phosphatase was required for optimal Atg13 dephosphorylation, pre-autophagosomal structure formation, and autophagy induction after TORC1 inactivation. In addition, Cdc14 was required for sufficient induction of ATG8 and ATG13 expression. Moreover, Cdc14 activation provoked autophagy even under normal conditions. This study identified a novel role of Cdc14 as the stress-responsive phosphatase for autophagy induction in budding yeast.
Cdc14 蛋白磷酸酶对于芽殖酵母的后期有丝分裂进展至关重要，尽管其在其他生物体（包括哺乳动物细胞）中的同源物作为应激响应磷酸酶发挥作用。我们在此发现 Cdc14 在营养饥饿后诱导自噬和雷帕霉素复合物 1 (TORC1) 激酶失活中的意外作用。TORC1 激酶通过磷酸化 Atg13 来抑制营养丰富条件下的自噬，但如果 TORC1 在营养饥饿或雷帕霉素处理时失活，则 Atg13 会迅速去磷酸化，自噬被诱导。Cdc14 磷酸酶对于最佳的 Atg13 去磷酸化、前自噬体结构形成和 TORC1 失活后的自噬诱导是必需的。此外，Cdc14 对于 ATG8 和 ATG13 表达的充分诱导也是必需的。此外，Cdc14 的激活甚至在正常条件下也会引发自噬。这项研究确定了 Cdc14 在芽殖酵母中作为应激响应磷酸酶诱导自噬的新作用。
