Signalling pathways in the induction of proteasome expression by proteolysis-inducing factor in murine myotubes

Stacey M. Wyke, Jwan Khal, Michael J. Tisdale*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

The mechanism by which the tumour product proteolysis-inducing factor (PIF) induced increased expression of the ubiquitin-proteasome proteolytic pathway was studied in C2C12 murine myotubes. PIF directly increased total protein breakdown at concentrations between 4 and 16 nM, and the effect was attenuated by eicosapentaenoic acid (EPA) and the 12/15-lipoxygenase inhibitor 2,3,5-trimethyl-6-(3-pyridylmethyl)1,4-benzoquinone (CV-6504). PIF induced an increased expression of mRNA for proteasome α (C2) and β (C5) subunits over the same concentration range as that inducing protein degradation and with a maximal effect 4 h after PIF addition. The effect was attenuated by both EPA and CV-6504, suggesting the role of a lipoxygenase metabolite in the increased gene transcription. 15(S)-Hydroxyeicosatetraenoic acid [15(S)-HETE], an intermediate in intracellular signalling by PIF was shown to activate protein kinase Cα(PKC) over the same concentration range as that inducing proteasome expression and both effects were attenuated by calphostin C, a highly specific inhibitor of PKC. 15(S)-HETE induced phosphorylation and degradation of IκBα at the same concentrations as those inducing 20S proteasome expression, and this effect was attenuated by calphostin C, suggesting the mediation of PKC. These results suggest potential control points in proteasome activation that could be useful for therapeutic intervention.

Original languageEnglish
Pages (from-to)67-75
Number of pages9
JournalCellular Signalling
Volume17
Issue number1
DOIs
Publication statusPublished - 1 Jan 2005

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Skeletal Muscle Fibers
Proteasome Endopeptidase Complex
Proteolysis
Protein Kinase C
Hydroxyeicosatetraenoic Acids
Lipoxygenase Inhibitors
Eicosapentaenoic Acid
Lipoxygenase
Ubiquitin
Phosphorylation
Messenger RNA
Genes
Neoplasms
Proteins

Keywords

  • 15(S)-HETE
  • 15-hydroxyeicosatetraenoic acid
  • eicosapentaenoic acid
  • EPA
  • Hydroxyeicosatetraenoic acid (15-HETE)
  • PIF
  • PKC
  • Proteasome proteolysis
  • Protein degradation
  • Protein kinase C
  • proteolysis-inducing factor
  • Proteolysis-inducing factor (PIF)

Cite this

Wyke, Stacey M. ; Khal, Jwan ; Tisdale, Michael J. / Signalling pathways in the induction of proteasome expression by proteolysis-inducing factor in murine myotubes. In: Cellular Signalling. 2005 ; Vol. 17, No. 1. pp. 67-75.
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abstract = "The mechanism by which the tumour product proteolysis-inducing factor (PIF) induced increased expression of the ubiquitin-proteasome proteolytic pathway was studied in C2C12 murine myotubes. PIF directly increased total protein breakdown at concentrations between 4 and 16 nM, and the effect was attenuated by eicosapentaenoic acid (EPA) and the 12/15-lipoxygenase inhibitor 2,3,5-trimethyl-6-(3-pyridylmethyl)1,4-benzoquinone (CV-6504). PIF induced an increased expression of mRNA for proteasome α (C2) and β (C5) subunits over the same concentration range as that inducing protein degradation and with a maximal effect 4 h after PIF addition. The effect was attenuated by both EPA and CV-6504, suggesting the role of a lipoxygenase metabolite in the increased gene transcription. 15(S)-Hydroxyeicosatetraenoic acid [15(S)-HETE], an intermediate in intracellular signalling by PIF was shown to activate protein kinase Cα(PKC) over the same concentration range as that inducing proteasome expression and both effects were attenuated by calphostin C, a highly specific inhibitor of PKC. 15(S)-HETE induced phosphorylation and degradation of IκBα at the same concentrations as those inducing 20S proteasome expression, and this effect was attenuated by calphostin C, suggesting the mediation of PKC. These results suggest potential control points in proteasome activation that could be useful for therapeutic intervention.",
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Signalling pathways in the induction of proteasome expression by proteolysis-inducing factor in murine myotubes. / Wyke, Stacey M.; Khal, Jwan; Tisdale, Michael J.

In: Cellular Signalling, Vol. 17, No. 1, 01.01.2005, p. 67-75.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Signalling pathways in the induction of proteasome expression by proteolysis-inducing factor in murine myotubes

AU - Wyke, Stacey M.

AU - Khal, Jwan

AU - Tisdale, Michael J.

PY - 2005/1/1

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N2 - The mechanism by which the tumour product proteolysis-inducing factor (PIF) induced increased expression of the ubiquitin-proteasome proteolytic pathway was studied in C2C12 murine myotubes. PIF directly increased total protein breakdown at concentrations between 4 and 16 nM, and the effect was attenuated by eicosapentaenoic acid (EPA) and the 12/15-lipoxygenase inhibitor 2,3,5-trimethyl-6-(3-pyridylmethyl)1,4-benzoquinone (CV-6504). PIF induced an increased expression of mRNA for proteasome α (C2) and β (C5) subunits over the same concentration range as that inducing protein degradation and with a maximal effect 4 h after PIF addition. The effect was attenuated by both EPA and CV-6504, suggesting the role of a lipoxygenase metabolite in the increased gene transcription. 15(S)-Hydroxyeicosatetraenoic acid [15(S)-HETE], an intermediate in intracellular signalling by PIF was shown to activate protein kinase Cα(PKC) over the same concentration range as that inducing proteasome expression and both effects were attenuated by calphostin C, a highly specific inhibitor of PKC. 15(S)-HETE induced phosphorylation and degradation of IκBα at the same concentrations as those inducing 20S proteasome expression, and this effect was attenuated by calphostin C, suggesting the mediation of PKC. These results suggest potential control points in proteasome activation that could be useful for therapeutic intervention.

AB - The mechanism by which the tumour product proteolysis-inducing factor (PIF) induced increased expression of the ubiquitin-proteasome proteolytic pathway was studied in C2C12 murine myotubes. PIF directly increased total protein breakdown at concentrations between 4 and 16 nM, and the effect was attenuated by eicosapentaenoic acid (EPA) and the 12/15-lipoxygenase inhibitor 2,3,5-trimethyl-6-(3-pyridylmethyl)1,4-benzoquinone (CV-6504). PIF induced an increased expression of mRNA for proteasome α (C2) and β (C5) subunits over the same concentration range as that inducing protein degradation and with a maximal effect 4 h after PIF addition. The effect was attenuated by both EPA and CV-6504, suggesting the role of a lipoxygenase metabolite in the increased gene transcription. 15(S)-Hydroxyeicosatetraenoic acid [15(S)-HETE], an intermediate in intracellular signalling by PIF was shown to activate protein kinase Cα(PKC) over the same concentration range as that inducing proteasome expression and both effects were attenuated by calphostin C, a highly specific inhibitor of PKC. 15(S)-HETE induced phosphorylation and degradation of IκBα at the same concentrations as those inducing 20S proteasome expression, and this effect was attenuated by calphostin C, suggesting the mediation of PKC. These results suggest potential control points in proteasome activation that could be useful for therapeutic intervention.

KW - 15(S)-HETE

KW - 15-hydroxyeicosatetraenoic acid

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KW - Hydroxyeicosatetraenoic acid (15-HETE)

KW - PIF

KW - PKC

KW - Proteasome proteolysis

KW - Protein degradation

KW - Protein kinase C

KW - proteolysis-inducing factor

KW - Proteolysis-inducing factor (PIF)

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M3 - Article

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AN - SCOPUS:4644313603

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JO - Cellular Signalling

JF - Cellular Signalling

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