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Regulation of autophagic flux by CHIP

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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.

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Authors and Affiliations

  1. Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215021, China

    Dongkai Guo, Zheng Ying, Hongfeng Wang, Dong Chen, Feng Gao, Haigang Ren & Guanghui Wang

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  1. Dongkai Guo
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  2. Zheng Ying
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  3. Hongfeng Wang
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  6. Haigang Ren
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  7. Guanghui Wang
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Correspondence to Haigang Ren or Guanghui Wang.

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Guo, D., Ying, Z., Wang, H. et al. Regulation of autophagic flux by CHIP. Neurosci. Bull. 31, 469–479 (2015). https://doi.org/10.1007/s12264-015-1543-7

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