SIRT4 regulates PTEN stability through IDE in response to cellular stresses
SIRT4 regulates PTEN stability through IDE in response to cellular stresses
复制标题
SIRT4 通过 IDE 调节 PTEN 稳定性以应对细胞应激
DOI：
10.1096/fj.201801987r
复制
发表时间：
2019-04-01
期刊：
影响因子：
4.8
通讯作者：
Luo, Jianyuan
中科院分区：
文献类型：
--
作者：
Liu, Minghui;Wang, Zhe;Luo, Jianyuan
10号染色体上缺失的肿瘤抑制性磷酸酶和张力蛋白同源物（PTEN）通过拮抗PI 3 K-AKT-mTOR途径在调节细胞存活、细胞生长和增殖中起关键作用。PTEN蛋白的调控机制目前还不完全清楚。在这里，我们发现Sirtuin 4（SIRT 4）与PTEN相互作用并调节其稳定性。SIRT 4在细胞中的过表达导致PTEN的下调。这种调节不依赖于PTEN乙酰化和泛素化。我们进一步发现SIRT 4通过胰岛素降解酶（IDE）介导的溶酶体途径降解PTEN。SIRT 4桥接PTEN和IDE以响应营养饥饿应激而降解。我们的研究结果表明，当细胞暴露于营养饥饿，SIRT 4被诱导和IDE合作降解PTEN;低水平的PTEN促进细胞从细胞应激中存活。我们的研究结果提供了一个新的调节PTEN在细胞应激反应。
Tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) plays a critical role in regulating cell survival, cell growth, and proliferation by antagonizing the PI3K-AKT-mTOR pathway. The regulatory mechanism of PTEN protein is still not completely understood. Here, we found that Sirtuin 4 (SIRT4) interacts with PTEN and regulates its stability. Overexpression of SIRT4 in cells causes down-regulation of PTEN. This regulation is independent of PTEN acetylation and ubiquitination. We further found that SIRT4 degrades PTEN through lysosome pathway mediated by insulin degrading enzyme (IDE). SIRT4 bridges PTEN and IDE for degradation in response to nutritional starvation stresses. Our results suggest that when cells were exposed to nutritional starvation, SIRT4 was induced and cooperated with IDE to degrade PTEN; low levels of PTEN promote cells to survive from cellular stress. Our findings provide a new regulation of PTEN in response to cellular stresses.