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. 2015 Jul 28;31(4):469–479. doi: 10.1007/s12264-015-1543-7

Regulation of autophagic flux by CHIP

Dongkai Guo 1, Zheng Ying 1, Hongfeng Wang 1, Dong Chen 1, Feng Gao 1, Haigang Ren 1,✉, Guanghui Wang 1,✉
PMCID: PMC5563714  PMID: 26219223

Abstract

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.

Keywords: CHIP/STUB1, autophagic flux, neurodegeneration, mTOR, AKT

Contributor Information

Haigang Ren, Email: rhg@suda.edu.cn.

Guanghui Wang, Email: wanggh@suda.edu.cn.

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