LSD1 negatively regulates autophagy in myoblast cells by driving PTEN degradation
LSD1 negatively regulates autophagy in myoblast cells by driving PTEN degradation
复制标题
LSD1 通过驱动 PTEN 降解来负向调节成肌细胞的自噬。
DOI：
10.1016/j.bbrc.2019.11.182
复制
发表时间：
2020-02-19
影响因子：
3.1
通讯作者：
Gao, Yan-fei
中科院分区：
文献类型：
--
作者：
Shi, Ying-xu;He, Yan-ji;Gao, Yan-fei
赖氨酸特异性去甲基酶1 （LSD1）是一种转录调节因子，在染色质上起作用，从组蛋白3 （H3K4或H3K9）的赖氨酸4或赖氨酸9中去除单甲基和二甲基。LSD1还通过靶向参与多种生物过程的非组蛋白底物而具有非转录活性。在本报告中，我们确定LSD1通过转录不依赖的机制促进PTEN降解，从而负向调节骨骼肌细胞的自噬。在C2C12细胞中，LSD1抑制或缺失显著诱导自噬的开始；LSD1抑制导致的自噬与AKT/mTORC1失活有关。值得注意的是，PTEN（一种重要的抑制性AKT调节剂）的蛋白通过LSD1抑制得到稳定，尽管其mRNA水平降低。进一步的数据表明，LSD1与PTEN蛋白相互作用，增强其泛素化和降解。总之，我们的研究结果确定了LSD1在自噬中的一种新的生物学功能，通过调节PTEN的稳定性和AKT/mTORC1的活性来介导。(C) 2019 Elsevier Inc.版权所有。
Lysine-specific demethylase 1 (LSD1) is a well characterized transcriptional regulator functioning on the chromatin to remove mono- and di-methyl groups from lysine 4 or lysine 9 of histone 3 (H3K4 or H3K9). LSD1 also has non-transcriptional activities via targeting non-histone substrates that participate in diverse biological processes. In this report, we determined that LSD1 negatively regulates autophagy in skeletal muscle cells by promoting PTEN degradation in a transcription-independent mechanism. In C2C12 cells, LSD1 inhibition or depletion significantly induced the initiation of autophagy; and autophagy resulted from LSD1 inhibition is associated with AKT/mTORC1 inactivation. Notably, the proteins of PTEN, a prominent repressive AKT modulator, are stabilized by LSD1 inhibition despite a decrease of its mRNA levels. Further data demonstrated that LSD1 interacts with PTEN protein and enhances its ubiquitination and degradation. Together, our findings identify a novel biological function of LSD1 in autophagy, mediated by regulating the stability of PTEN and the activity of AKT/mTORC1. (C) 2019 Elsevier Inc. All rights reserved.