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Protein folding mediated by the Hsp70 family of molecular chaperones requires both ATP and the co-chaperone Hdj-1. BAG-1 was recently identified as a bcl-2-interacting, anti-apoptotic protein that binds to the ATPase domain of Hsp70 and prevents the release of the substrate. While this suggested that cells had the potential to modulate Hsp70-mediated protein folding, physiological regulators of BAG-1 have yet to be identified. We report here that the apoptotic regulator Scythe, originally isolated through binding to the potent apoptotic inducer Reaper, shares limited sequence identity with BAG-1 and inhibits Hsp70- mediated protein refolding. Scythe-mediated inhibition of Hsp70 is reversed by Reaper, providing evidence for the regulated reversible inhibition of chaperone activity. As Scythe functions downstream of Reaper in apoptotic induction, these findings suggest that Scythe/Reaper may signal apoptosis, in part through regulating the folding and activity of apoptotic signaling molecules.
Adams,
The Bcl-2 protein family: arbiters of cell survival.
1998, Pubmed
Adams,
The Bcl-2 protein family: arbiters of cell survival.
1998,
Pubmed Adams,
The genome sequence of Drosophila melanogaster.
2000,
Pubmed Bardelli,
HGF receptor associates with the anti-apoptotic protein BAG-1 and prevents cell death.
1996,
Pubmed Bimston,
BAG-1, a negative regulator of Hsp70 chaperone activity, uncouples nucleotide hydrolysis from substrate release.
1998,
Pubmed Demand,
The carboxy-terminal domain of Hsc70 provides binding sites for a distinct set of chaperone cofactors.
1998,
Pubmed Desagher,
Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis.
1999,
Pubmed Evans,
Reaper-induced apoptosis in a vertebrate system.
1997,
Pubmed
,
Xenbase Freeman,
The human cytosolic molecular chaperones hsp90, hsp70 (hsc70) and hdj-1 have distinct roles in recognition of a non-native protein and protein refolding.
1996,
Pubmed Gross,
Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-XL prevents this release but not tumor necrosis factor-R1/Fas death.
1999,
Pubmed Hartl,
Molecular chaperones in cellular protein folding.
1996,
Pubmed Höhfeld,
Hip, a novel cochaperone involved in the eukaryotic Hsc70/Hsp40 reaction cycle.
1995,
Pubmed Höhfeld,
GrpE-like regulation of the hsc70 chaperone by the anti-apoptotic protein BAG-1.
1997,
Pubmed Jasny,
The universe of Drosophila genes.
2000,
Pubmed Kaye,
A family of ubiquitin-like proteins binds the ATPase domain of Hsp70-like Stch.
2000,
Pubmed
,
Xenbase Lewis,
Purification and biochemical properties of soluble recombinant human Bax.
1998,
Pubmed Lüders,
Distinct isoforms of the cofactor BAG-1 differentially affect Hsc70 chaperone function.
2000,
Pubmed Lüders,
The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome.
2000,
Pubmed McCarthy,
Apoptosis induced by Drosophila reaper and grim in a human system. Attenuation by inhibitor of apoptosis proteins (cIAPs).
1998,
Pubmed Minami,
Regulation of the heat-shock protein 70 reaction cycle by the mammalian DnaJ homolog, Hsp40.
1996,
Pubmed Nollen,
Bag1 functions in vivo as a negative regulator of Hsp70 chaperone activity.
2000,
Pubmed Rassow,
Partner proteins determine multiple functions of Hsp70.
1995,
Pubmed Rüdiger,
Interaction of Hsp70 chaperones with substrates.
1997,
Pubmed Shimizu,
Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC.
1999,
Pubmed Song,
Bag1-Hsp70 mediates a physiological stress signalling pathway that regulates Raf-1/ERK and cell growth.
2001,
Pubmed Stuart,
Characterization of interactions between the anti-apoptotic protein BAG-1 and Hsc70 molecular chaperones.
1998,
Pubmed Takayama,
BAG-1 modulates the chaperone activity of Hsp70/Hsc70.
1997,
Pubmed Takayama,
An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators.
1999,
Pubmed Takayama,
Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity.
1995,
Pubmed Thress,
Scythe: a novel reaper-binding apoptotic regulator.
1998,
Pubmed
,
Xenbase Thress,
Reaper-induced dissociation of a Scythe-sequestered cytochrome c-releasing activity.
1999,
Pubmed
,
Xenbase Wang,
Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1.
1996,
Pubmed White,
Genetic control of programmed cell death in Drosophila.
1994,
Pubmed White,
Cell killing by the Drosophila gene reaper.
1996,
Pubmed Zeiner,
A protein that interacts with members of the nuclear hormone receptor family: identification and cDNA cloning.
1995,
Pubmed Zha,
BH3 domain of BAD is required for heterodimerization with BCL-XL and pro-apoptotic activity.
1997,
Pubmed
