Cdc14 Phosphatase Promotes TORC1-Regulated Autophagy in Yeast
Cdc14 Phosphatase Promotes TORC1-Regulated Autophagy in Yeast
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Cdc14 磷酸酶促进酵母中 TORC1 调节的自噬
DOI：
10.1016/j.jmb.2018.04.007
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发表时间：
2018
影响因子：
5.6
通讯作者：
Ushimaru Takashi
中科院分区：
文献类型：
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作者：
Kondo Akihiro;Mostofa Md. Golam;Miyake Katsuya;Terasawa Mashu;Nafisa Islam;Yeasmin Akter M.S.T.;Waliullah Talukdar Muhammad;Kanki Tomotake;Ushimaru Takashi
虽然CDC14蛋白磷酸酶在包括哺乳动物细胞在内的其他生物中具有应激反应磷酸酶的功能，但它对芽期酵母的后期有丝分裂进程是至关重要的。我们在此发现，在营养饥饿和雷帕霉素复合体1(TORC1)激酶失活的靶点后，CDC14在自噬诱导中发挥了意想不到的作用。在营养丰富的条件下，TORC1激酶使ATG13磷酸化以抑制自噬，但如果TORC1在营养饥饿或雷帕霉素处理后变得不活跃，ATG13迅速去磷酸化并诱导自噬。在TORC1失活后，最适的Atg13去磷酸化、自噬前结构的形成和自噬的诱导都需要CDC14磷酸酶。此外，CDC14是充分诱导ATG8和ATG13表达所必需的。此外，即使在正常条件下，CDC14的激活也会引发自噬。这项研究确定了一个新的作用，即CDC14作为应激反应磷酸酶在芽殖酵母中诱导自噬。
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 ofATG8andATG13expression. 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.