Reversible inhibition of Hsp70 chaperone function by Scythe and Reaper

Kenneth Thress, Jaewhan Song, Richard I. Morimoto, Sally Kornbluth

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Protein folding mediated by the Hsp70 family of molecular chaperones requires both ATP and the cochaperone 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.

Original languageEnglish
Pages (from-to)1033-1041
Number of pages9
JournalEMBO Journal
Volume20
Issue number5
DOIs
Publication statusPublished - 2001 Mar 1

Fingerprint

Protein folding
Protein Folding
Protein Refolding
Apoptosis Regulatory Proteins
Molecular Chaperones
Adenosine Triphosphatases
Adenosine Triphosphate
Apoptosis
Molecules
Substrates
Proteins

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Thress, Kenneth ; Song, Jaewhan ; Morimoto, Richard I. ; Kornbluth, Sally. / Reversible inhibition of Hsp70 chaperone function by Scythe and Reaper. In: EMBO Journal. 2001 ; Vol. 20, No. 5. pp. 1033-1041.
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Reversible inhibition of Hsp70 chaperone function by Scythe and Reaper. / Thress, Kenneth; Song, Jaewhan; Morimoto, Richard I.; Kornbluth, Sally.

In: EMBO Journal, Vol. 20, No. 5, 01.03.2001, p. 1033-1041.

Research output: Contribution to journalArticle

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