Protein phosphatase 6 dissociates the Beclin 1/Vps34 complex and inhibits autophagy
Protein phosphatase 6 dissociates the Beclin 1/Vps34 complex and inhibits autophagy
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DOI：
10.1016/j.bbrc.2021.02.136
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发表时间：
2021-03-20
影响因子：
3.1
通讯作者：
Sato, Koichi
中科院分区：
文献类型：
--
作者：
Fujiwara, Nobuyuki;Shibutani, Shusaku;Sato, Koichi
自噬是一种进化上保守的细胞内降解系统，受到多种信号通路的调节，包括 Beclin 1/Vacuolar 蛋白分选 34 (Vps34) 复合体。蛋白磷酸酶 6 (PP6) 是一种重要的丝氨酸/苏氨酸磷酸酶，可调节多种生物过程。最近，我们发现PP6蛋白被p62依赖性选择性自噬降解。在这项研究中，我们发现 PP6 反过来抑制自噬。 PP6 与 Beclin 1 的 C 末端区域结合，该区域靠近 Vps34 的结合区域。 PP6 的蛋白水平影响 Beclin 1/Vps34 复合物的形成，而 PP6 的磷酸酶活性不参与其中。我们还表明，化学诱导的 PP6/Beclin 1 关联会导致 Vps34 从 Beclin 1 解离。总的来说，我们的数据揭示了 PP6 的自噬新调控机制。(c) 2021 Elsevier Inc. 保留所有权利。
Autophagy is an evolutionarily conserved intracellular degradation system and is regulated by various signaling pathways including the Beclin 1/Vacuolar protein sorting 34 (Vps34) complex. Protein phos-phatase 6 (PP6) is an essential serine/threonine phosphatase that regulates various biological processes. Recently, we found that PP6 protein is degraded by p62-dependent selective autophagy. In this study, we show that PP6 conversely inhibits autophagy. PP6 associate with the C-terminal region of Beclin 1, which is close to the binding region of Vps34. The protein levels of PP6 affect Beclin 1/Vps34 complex formation and phosphatase activity of PP6 is not involved in this. We also show that chemically induced PP6/Beclin 1 association leads to Vps34 dissociation from Beclin 1. Overall, our data reveal a novel regulatory mechanism for autophagy by PP6.(c) 2021 Elsevier Inc. All rights reserved.