Autophagy regulates levels of tumor suppressor enzyme protein phosphatase 6.
Autophagy regulates levels of tumor suppressor enzyme protein phosphatase 6.
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DOI：
10.1111/cas.14662
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发表时间：
2020-12
期刊：
影响因子：
5.7
通讯作者：
Sato K
中科院分区：
文献类型：
--
作者：
Fujiwara N;Shibutani S;Sakai Y;Watanabe T;Kitabayashi I;Oshima H;Oshima M;Hoshida H;Akada R;Usui T;Ohama T;Sato K
蛋白磷酸酶6（PP 6）是一种重要的丝氨酸/苏氨酸蛋白磷酸酶，具有重要的肿瘤抑制作用。然而，在某些癌症类型中观察到PP 6蛋白水平升高，并且它们与胶质母细胞瘤的不良预后相关。这就提出了一个关于PP 6蛋白水平在正常细胞和转化细胞中是如何调节的问题。在这项研究中，我们表明PP 6蛋白水平增加响应于自噬的药理学和遗传抑制。PP 6与自噬衔接蛋白p62/SQSTM 1结合，并以p62依赖性方式降解。因此，PP 6和p62的蛋白水平在不同的生理和病理生理条件下一致波动。我们的数据显示，PP 6受p62依赖性自噬的调节，并表明PP 6蛋白在肿瘤组织中的积累至少部分是由自噬缺陷引起的。蛋白磷酸酶6（PP 6）是一种重要的丝氨酸/苏氨酸蛋白磷酸酶，具有重要的肿瘤抑制作用。然而，在一些癌症类型中观察到PP 6蛋白水平升高，并且与胶质母细胞瘤的不良预后相关。我们的数据显示，PP 6受p62依赖性自噬的调节，并表明PP 6蛋白在肿瘤组织中的积累至少部分是由自噬缺陷引起的。
Protein phosphatase 6 (PP6) is an essential serine/threonine protein phosphatase that acts as an important tumor suppressor. However, increased protein levels of PP6 have been observed in some cancer types, and they correlate with poor prognosis in glioblastoma. This raises a question about how PP6 protein levels are regulated in normal and transformed cells. In this study, we show that PP6 protein levels increase in response to pharmacologic and genetic inhibition of autophagy. PP6 associates with autophagic adaptor protein p62/SQSTM1 and is degraded in a p62‐dependent manner. Accordingly, protein levels of PP6 and p62 fluctuate in concert under different physiological and pathophysiological conditions. Our data reveal that PP6 is regulated by p62‐dependent autophagy and suggest that accumulation of PP6 protein in tumor tissues is caused at least partially by deficiency in autophagy. Protein phosphatase 6 (PP6) is an essential serine/threonine protein phosphatase that acts as an important tumor suppressor. However, increased protein levels of PP6 have been observed in some cancer types, and correlate with poor prognosis in glioblastoma. Our data reveal that PP6 is regulated by p62‐dependent autophagy and suggest that accumulation of PP6 protein in tumor tissues is caused at least partially by deficiency in autophagy.
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影响因子：
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