title: Regulation of autophagic flux by CHIP.
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.
authors.affiliation: 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.
authors.forename: Dongkai
authors.initials: D
authors.lastname: Guo
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ying
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Haigang
authors.initials: H
authors.lastname: Ren
authors.forename: Guanghui
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D001343:Autophagy; D057809:HEK293 Cells; D006801:Humans; D064688:Metabolic Flux Analysis; D051379:Mice; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D016601:RNA-Binding Proteins; D058570:TOR Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; C118585:P62 protein, human; C467728:STUB1 protein, human; C546842:MTOR protein, human