Regulation of autophagic flux by CHIP

Autophagy is a major degradation system which processes substrates through the steps of auto- phagosome formation, autophagosome-lysosome fusion, and substrate degradation. Aberrant autophagic flux is present in many pathological conditions including neurodegeneration and tumors. CHIP/STUB1, an E3 l...

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Published inNeuroscience bulletin Vol. 31; no. 4; pp. 469 - 479
Main Authors Guo, Dongkai, Ying, Zheng, Wang, Hongfeng, Chen, Dong, Gao, Feng, Ren, Haigang, Wang, Guanghui
Format Journal Article
LanguageEnglish
Published Shanghai Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences 01.08.2015
Subjects
Anatomy
Anesthesiology
Animals
Autophagy
Biomedical and Life Sciences
Biomedicine
HEK293 Cells
Human Physiology
Humans
Metabolic Flux Analysis
Mice
Neurology
Neurosciences
Oncogene Protein v-akt - metabolism
Original
Original Article
Pain Medicine
Phosphatidylinositol 3-Kinases - metabolism
RNA-Binding Proteins - metabolism
Signal Transduction
TOR Serine-Threonine Kinases - metabolism
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
Ubiquitin-Protein Ligases - physiology
基因芯片
基质降解
相互作用
神经退行性疾病
细胞死亡
自噬
蛋白水平
调节流量
autophagic flux
neurodegeneration
mTOR
AKT
CHIP/STUB1
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Summary:Autophagy is a major degradation system which processes substrates through the steps of auto- phagosome 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 HscT0-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 AI. Thus, our data suggest that CHIP plays roles in the regulation of autophagic flux.
Bibliography:Autophagy is a major degradation system which processes substrates through the steps of auto- phagosome 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 HscT0-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 AI. Thus, our data suggest that CHIP plays roles in the regulation of autophagic flux.
CHIP/STUB1; autophagic flux; neuro-degeneration; mTOR; AKT
31-1975/R
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1673-7067
1995-8218
DOI:10.1007/s12264-015-1543-7