Reversible inhibition of Hsp70 chaperone function by Scythe and Reaper.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Thress, K; Song, J; Morimoto, RI; Kornbluth, S

Published Date

  • March 1, 2001

Published In

Volume / Issue

  • 20 / 5

Start / End Page

  • 1033 - 1041

PubMed ID

  • 11230127

International Standard Serial Number (ISSN)

  • 0261-4189

Digital Object Identifier (DOI)

  • 10.1093/emboj/20.5.1033

Language

  • eng

Conference Location

  • England