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Hsp83 loss suppresses proteasomal activity resulting in an upregulation of caspase-dependent compensatory autophagy
- Source :
- Autophagy
- Publication Year :
- 2017
- Publisher :
- Landes Bioscience, 2017.
-
Abstract
- The 2 main degradative pathways that contribute to proteostasis are the ubiquitin-proteasome system and autophagy but how they are molecularly coordinated is not well understood. Here, we demonstrate an essential role for an effector caspase in the activation of compensatory autophagy when proteasomal activity is compromised. Functional loss of Hsp83, the Drosophila ortholog of human HSP90 (heat shock protein 90), resulted in reduced proteasomal activity and elevated levels of the effector caspase Dcp-1. Surprisingly, genetic analyses showed that the caspase was not required for cell death in this context, but instead was essential for the ensuing compensatory autophagy, female fertility, and organism viability. The zymogen pro-Dcp-1 was found to interact with Hsp83 and undergo proteasomal regulation in an Hsp83-dependent manner. Our work not only reveals unappreciated roles for Hsp83 in proteasomal activity and regulation of Dcp-1, but identifies an effector caspase as a key regulatory factor for sustaining adaptation to cell stress in vivo.
- Subjects :
- Proteomics
0301 basic medicine
Proteasome Endopeptidase Complex
Programmed cell death
caspase
Mass Spectrometry
03 medical and health sciences
Downregulation and upregulation
compensatory autophagy
Heat shock protein
Autophagy
In Situ Nick-End Labeling
Animals
Drosophila Proteins
Molecular Biology
Heat-Shock Proteins
Caspase
Ovum
biology
Effector
apoptosis
Cell Biology
heat-shock protein
Hsp83
Basic Research Paper
Up-Regulation
Cell biology
Protein Subunits
Drosophila melanogaster
Fertility
030104 developmental biology
Proteostasis
Proteasome
Caspases
Larva
Mutation
Dcp-1
Cancer research
biology.protein
Drosophila
Female
Mutant Proteins
RNA Interference
ubiquitin-proteasome system
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Autophagy
- Accession number :
- edsair.doi.dedup.....331f82eb3a22d51cc92fa57ec048f52a