蛋白磷酸酶 6 使 Beclin 1/Vps34 复合物解体并抑制自噬。
Protein phosphatase 6 dissociates the Beclin 1/Vps34 complex and inhibits autophagy.
机构信息
Laboratory of Veterinary Pharmacology, 753-8515, Yamaguchi, Japan; Laboratory of Drug Discovery and Pharmacology, Faculty of Veterinary Medicine, Okayama University of Science, 794-8555, Ehime, Japan.
Laboratory of Veterinary Hygiene, Yamaguchi University, 753-8515, Yamaguchi, Japan.
出版信息
Biochem Biophys Res Commun. 2021 May 7;552:191-195. doi: 10.1016/j.bbrc.2021.02.136. Epub 2021 Mar 20.
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 phosphatase 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.
自噬是一种进化上保守的细胞内降解系统，受多种信号通路调节，包括 Beclin 1/Vacuolar 蛋白分选 34（Vps34）复合物。蛋白磷酸酶 6（PP6）是一种必需的丝氨酸/苏氨酸磷酸酶，调节多种生物过程。最近，我们发现 PP6 蛋白通过 p62 依赖性选择性自噬降解。在这项研究中，我们表明 PP6 反而抑制自噬。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 结合导致 Vps34 从 Beclin 1 解离。总的来说，我们的数据揭示了 PP6 对自噬的一种新的调节机制。
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