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HSF1 stress response pathway regulates autophagy receptor SQSTM1/p62-associated proteostasis
- Source :
- Autophagy
- Publication Year :
- 2017
- Publisher :
- Informa UK Limited, 2017.
-
Abstract
- Proteostasis is important for protecting cells from harmful proteins and is mainly controlled by the HSF1 (heat shock transcription factor 1) stress response pathway. This pathway facilitates protein refolding by molecular chaperones; however, it is unclear whether it functions in autophagy or inclusion formation. The autophagy receptor SQSTM1/p62 is involved in selective autophagic clearance and inclusion formation by harmful proteins, and its phosphorylation at S349, S403, and S407 is required for binding to substrates. Here, we demonstrate that casein kinase 1 phosphorylates the SQSTM1 S349 residue when harmful proteins accumulate. Investigation of upstream factors showed that both SQSTM1 S349 and SQSTM1 S403 residues were phosphorylated in an HSF1 dependent manner. Inhibition of SQSTM1 phosphorylation suppressed inclusion formation by ubiquitinated proteins and prevented colocalization of SQSTM1 with aggregation-prone proteins. Moreover, HSF1 inhibition impaired aggregate-induced autophagosome formation and elimination of protein aggregates. Our findings indicate that HSF1 triggers SQSTM1-mediated proteostasis.
- Subjects :
- 0301 basic medicine
Autophagosome
Proteasome Endopeptidase Complex
Protein Denaturation
Protein Folding
SQSTM1/p62
Aggrephagy
Biology
HSF1
Mice
03 medical and health sciences
0302 clinical medicine
Heat Shock Transcription Factors
Sequestosome-1 Protein
Autophagy
Animals
Humans
Phosphorylation
aggrephagy
Molecular Biology
Adaptor Proteins, Signal Transducing
Cell Nucleus
Mice, Knockout
proteostasis
Casein Kinase I
Cell Biology
Ubiquitinated Proteins
Basic Research Paper
Mice, Inbred C57BL
Heat shock factor
030104 developmental biology
Proteostasis
Biochemistry
Cytoprotection
Mutation
alpha-Synuclein
Casein kinase 1
casein kinase
030217 neurology & neurosurgery
HeLa Cells
Subjects
Details
- ISSN :
- 15548635 and 15548627
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Autophagy
- Accession number :
- edsair.doi.dedup.....897097c8bd789d3cf2bb2e6a0d96dc97