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
Y1 - 2005/1/1
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
KW - eicosapentaenoic acid
KW - EPA
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)
UR - http://www.scopus.com/inward/record.url?scp=4644313603&partnerID=8YFLogxK
UR - https://www.sciencedirect.com/science/article/pii/S0898656804001068?via%3Dihub
U2 - 10.1016/j.cellsig.2004.05.015
DO - 10.1016/j.cellsig.2004.05.015
M3 - Article
C2 - 15451026
AN - SCOPUS:4644313603
SN - 0898-6568
VL - 17
SP - 67
EP - 75
JO - Cellular Signalling
JF - Cellular Signalling
IS - 1
ER -