Inhibition of the multicatalytic proteinase (proteasome) by 4-hydroxy-2-nonenal cross-linked protein

Bertrand Friguet, Luke I. Szweda

Research output: Contribution to journalArticle

230 Citations (Scopus)

Abstract

Oxidative modification of glucose-6-phosphate dehydrogenase (Glu-6-PDH), as observed for other proteins, increases the susceptibility of the protein to degradation by the multicatalytic proteinase/proteasome (MCP). Oxidized Glu-6-PDH is, however, more prone to cross-linking reactions by the lipid peroxidation product 4-hydroxy-2-nonenal (HNE), processes which render the protein resistant to proteolysis. In addition, HNE cross-linked protein inhibits the degradation of oxidatively modified glutamine synthetase by the MCP. In contrast to oxidized Glu-6-PDH, which inhibits the proteolysis of GS in a competitive manner, HNE cross-linked protein acts as a noncompetitive inhibitor. As judged by binding of the hydrophobic fluorescent probe 8-anilino-1-naphthalenesulfonic acid, a common structural feature of both macromolecular substrates and inhibitors of the MCP is an increased accessibility of hydrophobic regions on the protein.

Original languageEnglish (US)
Pages (from-to)21-25
Number of pages5
JournalFEBS Letters
Volume405
Issue number1
DOIs
StatePublished - Mar 17 1997

Fingerprint

Proteasome Endopeptidase Complex
Proteolysis
Glucosephosphate Dehydrogenase
Proteins
Degradation
Glutamate-Ammonia Ligase
Cross Reactions
Fluorescent Dyes
Lipid Peroxidation
4-hydroxy-2-nonenal
Lipids
Substrates

Keywords

  • 4-Hydroxy-2-nonenal
  • Free radicals
  • Glucose-6-phosphate dehydrogenase
  • Hydrophobicity
  • Lipid peroxidation
  • Multicatalytic proteinase (20S proteasome)

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Inhibition of the multicatalytic proteinase (proteasome) by 4-hydroxy-2-nonenal cross-linked protein. / Friguet, Bertrand; Szweda, Luke I.

In: FEBS Letters, Vol. 405, No. 1, 17.03.1997, p. 21-25.

Research output: Contribution to journalArticle

@article{739dc8c23690433f9f67092df1bede97,
title = "Inhibition of the multicatalytic proteinase (proteasome) by 4-hydroxy-2-nonenal cross-linked protein",
abstract = "Oxidative modification of glucose-6-phosphate dehydrogenase (Glu-6-PDH), as observed for other proteins, increases the susceptibility of the protein to degradation by the multicatalytic proteinase/proteasome (MCP). Oxidized Glu-6-PDH is, however, more prone to cross-linking reactions by the lipid peroxidation product 4-hydroxy-2-nonenal (HNE), processes which render the protein resistant to proteolysis. In addition, HNE cross-linked protein inhibits the degradation of oxidatively modified glutamine synthetase by the MCP. In contrast to oxidized Glu-6-PDH, which inhibits the proteolysis of GS in a competitive manner, HNE cross-linked protein acts as a noncompetitive inhibitor. As judged by binding of the hydrophobic fluorescent probe 8-anilino-1-naphthalenesulfonic acid, a common structural feature of both macromolecular substrates and inhibitors of the MCP is an increased accessibility of hydrophobic regions on the protein.",
keywords = "4-Hydroxy-2-nonenal, Free radicals, Glucose-6-phosphate dehydrogenase, Hydrophobicity, Lipid peroxidation, Multicatalytic proteinase (20S proteasome)",
author = "Bertrand Friguet and Szweda, {Luke I.}",
year = "1997",
month = "3",
day = "17",
doi = "10.1016/S0014-5793(97)00148-8",
language = "English (US)",
volume = "405",
pages = "21--25",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Inhibition of the multicatalytic proteinase (proteasome) by 4-hydroxy-2-nonenal cross-linked protein

AU - Friguet, Bertrand

AU - Szweda, Luke I.

PY - 1997/3/17

Y1 - 1997/3/17

N2 - Oxidative modification of glucose-6-phosphate dehydrogenase (Glu-6-PDH), as observed for other proteins, increases the susceptibility of the protein to degradation by the multicatalytic proteinase/proteasome (MCP). Oxidized Glu-6-PDH is, however, more prone to cross-linking reactions by the lipid peroxidation product 4-hydroxy-2-nonenal (HNE), processes which render the protein resistant to proteolysis. In addition, HNE cross-linked protein inhibits the degradation of oxidatively modified glutamine synthetase by the MCP. In contrast to oxidized Glu-6-PDH, which inhibits the proteolysis of GS in a competitive manner, HNE cross-linked protein acts as a noncompetitive inhibitor. As judged by binding of the hydrophobic fluorescent probe 8-anilino-1-naphthalenesulfonic acid, a common structural feature of both macromolecular substrates and inhibitors of the MCP is an increased accessibility of hydrophobic regions on the protein.

AB - Oxidative modification of glucose-6-phosphate dehydrogenase (Glu-6-PDH), as observed for other proteins, increases the susceptibility of the protein to degradation by the multicatalytic proteinase/proteasome (MCP). Oxidized Glu-6-PDH is, however, more prone to cross-linking reactions by the lipid peroxidation product 4-hydroxy-2-nonenal (HNE), processes which render the protein resistant to proteolysis. In addition, HNE cross-linked protein inhibits the degradation of oxidatively modified glutamine synthetase by the MCP. In contrast to oxidized Glu-6-PDH, which inhibits the proteolysis of GS in a competitive manner, HNE cross-linked protein acts as a noncompetitive inhibitor. As judged by binding of the hydrophobic fluorescent probe 8-anilino-1-naphthalenesulfonic acid, a common structural feature of both macromolecular substrates and inhibitors of the MCP is an increased accessibility of hydrophobic regions on the protein.

KW - 4-Hydroxy-2-nonenal

KW - Free radicals

KW - Glucose-6-phosphate dehydrogenase

KW - Hydrophobicity

KW - Lipid peroxidation

KW - Multicatalytic proteinase (20S proteasome)

UR - http://www.scopus.com/inward/record.url?scp=0030977793&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030977793&partnerID=8YFLogxK

U2 - 10.1016/S0014-5793(97)00148-8

DO - 10.1016/S0014-5793(97)00148-8

M3 - Article

C2 - 9094417

AN - SCOPUS:0030977793

VL - 405

SP - 21

EP - 25

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 1

ER -