HSP70 mediates dissociation and reassociation of the 26S proteasome during adaptation to oxidative stress

Tilman Grune, Betül Catalgol, Anke Licht, Gennady Ermak, Andrew M. Pickering, Jenny K. Ngo, Kelvin J.A. Davies

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

We report an entirely new role for the HSP70 chaperone in dissociating 26S proteasome complexes (into free 20S proteasomes and bound 19S regulators), preserving 19S regulators, and reconstituting 26S proteasomes in the first 1-3 h after mild oxidative stress. These responses, coupled with direct 20S proteasome activation by poly(ADP ribose) polymerase in the nucleus and by PA28αβ in the cytoplasm, instantly provide cells with increased capacity to degrade oxidatively damaged proteins and to survive the initial effects of stress exposure. Subsequent adaptive (hormetic) processes (3-24 h after stress exposure), mediated by several signal transduction pathways and involving increased transcription/translation of 20S proteasomes, immunoproteasomes, and PA28αβ, abrogate the need for 26S proteasome dissociation. During this adaptive period, HSP70 releases its bound 19S regulators, 26S proteasomes are reconstituted, and ATP-stimulated proteolysis is restored. The 26S proteasome-dependent, and ATP-stimulated, turnover of ubiquitinylated proteins is essential for normal cell metabolism, and its restoration is required for successful stress adaptation.

Original languageEnglish (US)
Pages (from-to)1355-1364
Number of pages10
JournalFree Radical Biology and Medicine
Volume51
Issue number7
DOIs
StatePublished - Oct 1 2011

Keywords

  • Free radicals
  • Oxidative stress
  • Protein degradation
  • Protein oxidation
  • Stress adaptation
  • Ubiquitin-proteasome system

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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    Grune, T., Catalgol, B., Licht, A., Ermak, G., Pickering, A. M., Ngo, J. K., & Davies, K. J. A. (2011). HSP70 mediates dissociation and reassociation of the 26S proteasome during adaptation to oxidative stress. Free Radical Biology and Medicine, 51(7), 1355-1364. https://doi.org/10.1016/j.freeradbiomed.2011.06.015