Sequential interplay between BAG6 and HSP70 upon heat shock.
BAG6/Scythe/Bat3 is a cochaperone of the heat shock protein HSP70 and is involved in various developmental processes, cellular stress and viability. BAG6 interferes with the protein-refolding activity of HSP70 but its precise involvement in proteotoxic stresses remains unknown. We show that BAG6 is required for the accumulation of HSP70 upon heat shock and that conversely, once accumulated, HSP70 leads to the massive and CHIP-independent degradation of BAG6 through the ubiquitin-proteasome system. These reciprocal influences between BAG6 and HSP70 upon heat shock suggest that BAG6 is a central regulator of the cellular content of HSP70. The HSP70-driven degradation of BAG6, following the BAG6-dependent accumulation of HSP70, could allow the protein-refolding activity of HSP70 and limit the extent of its induction.
Corduan
A
A
Université de Rennes1, Interactions Cellulaires et Moléculaires UMR6026 CNRS-Hip-IFR140 GFAS, Bâtiment 13, Campus de Beaulieu, 35042, Rennes cedex, France.
Lecomte
S
S
Martin
C
C
Michel
D
D
Desmots
F
F
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D051379:Mice; D018832:Molecular Chaperones / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017510:Protein Folding; D011506:Proteins / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism
C092009:BAG6 protein, human; C484266:Bag6 protein, mouse; D002352:Carrier Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D011506:Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex