Regulation of autophagic flux by CHIP
Regulation of autophagic flux by CHIP
复制标题
CHIP 对自噬通量的调节
DOI：
10.1007/s12264-015-1543-7
复制
发表时间：
2015-08-01
影响因子：
5.6
通讯作者：
Wang, Guanghui
中科院分区：
文献类型：
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作者：
Guo, Dongkai;Ying, Zheng;Wang, Guanghui
自噬是一种主要的降解系统，它通过自噬小体形成、自噬小体-溶酶体融合和底物降解等步骤来处理底物。异常的自噬通量存在于许多病理情况，包括神经退行性变和肿瘤。CHIP/STUB1是一种E3连接酶，在神经退行性变中起重要作用。在本研究中，我们确定了CHIP(Hsc70相互作用蛋白的羧基末端)对自噬通量的调节。CHIP基因敲除通过增加PTEN蛋白水平、降低AKT/mTOR活性以及减少ULK1在Ser757上的磷酸化来诱导自噬小体的形成。然而，自噬底物p62的降解受到CHIP基因敲除的干扰，表明自噬通量异常。此外，CHIP的敲除增加了细胞对巴菲霉素A1诱导的自噬细胞死亡的敏感性。因此，我们的数据表明，CHIP在自噬通量的调节中发挥了作用。
Autophagy is a major degradation system which processes substrates through the steps of autophagosome formation, autophagosome-lysosome fusion, and substrate degradation. Aberrant autophagic flux is present in many pathological conditions including neurodegeneration and tumors. CHIP/STUB1, an E3 ligase, plays an important role in neurodegeneration. In this study, we identified the regulation of autophagic flux by CHIP (carboxy-terminus of Hsc70-interacting protein). Knockdown of CHIP induced autophagosome formation through increasing the PTEN protein level and decreasing the AKT/mTOR activity as well as decreasing phosphorylation of ULK1 on Ser757. However, degradation of the autophagic substrate p62 was disturbed by knockdown of CHIP, suggesting an abnormality of autophagic flux. Furthermore, knockdown of CHIP increased the susceptibility of cells to autophagic cell death induced by bafilomycin A1. Thus, our data suggest that CHIP plays roles in the regulation of autophagic flux.