Reversible inhibition of Hsp70 chaperone function by Scythe and Reaper.
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.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Xenopus Proteins
- Xenopus
- Transcription Factors
- Signal Transduction
- Sequence Homology, Amino Acid
- Sequence Alignment
- Recombinant Proteins
- Recombinant Fusion Proteins
- Protein Structure, Tertiary
- Protein Folding
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Xenopus Proteins
- Xenopus
- Transcription Factors
- Signal Transduction
- Sequence Homology, Amino Acid
- Sequence Alignment
- Recombinant Proteins
- Recombinant Fusion Proteins
- Protein Structure, Tertiary
- Protein Folding