Serdemetan Antagonizes the Mdm2-HIF1α Axis Leading to Decreased Levels of Glycolytic Enzymes

Jason A. Lehman, Paula M. Hauck, Jaimie M. Gendron, Christopher N. Batuello, Jacob A. Eitel, Allan Albig, Madhavi P. Kadakia, Lindsey Mayo

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Serdemetan (JNJ-26854165), an antagonist to Mdm2, was anticipated to promote the activation of p53. While regulation of p53 by Mdm2 is important, Mdm2 also regulates numerous proteins involved in diverse cellular functions. We investigated if Serdemetan would alter the Mdm2-HIF1α axis and affect cell survival in human glioblastoma cells independently of p53. Treatment of cells with Serdemetan under hypoxia resulted in a decrease in HIF1α levels. HIF1α downstream targets, VEGF and the glycolytic enzymes (enolase, phosphoglycerate kinase1/2, and glucose transporter 1), were all decreased in response to Serdemetan. The involvement of Mdm2 in regulating gene expression of glycolytic enzymes raises the possibility of side effects associated with therapeutically targeting Mdm2.

Original languageEnglish
Article numbere74741
JournalPLoS One
Volume8
Issue number9
DOIs
StatePublished - Sep 6 2013

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glucose transporters
phosphopyruvate hydratase
Enzymes
enzymes
cell viability
hypoxia
antagonists
adverse effects
cells
gene expression
Cells
Facilitative Glucose Transport Proteins
Phosphopyruvate Hydratase
Glioblastoma
Gene expression
proteins
Vascular Endothelial Growth Factor A
Cell Survival
Chemical activation
JNJ 26854165

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lehman, J. A., Hauck, P. M., Gendron, J. M., Batuello, C. N., Eitel, J. A., Albig, A., ... Mayo, L. (2013). Serdemetan Antagonizes the Mdm2-HIF1α Axis Leading to Decreased Levels of Glycolytic Enzymes. PLoS One, 8(9), [e74741]. https://doi.org/10.1371/journal.pone.0074741

Serdemetan Antagonizes the Mdm2-HIF1α Axis Leading to Decreased Levels of Glycolytic Enzymes. / Lehman, Jason A.; Hauck, Paula M.; Gendron, Jaimie M.; Batuello, Christopher N.; Eitel, Jacob A.; Albig, Allan; Kadakia, Madhavi P.; Mayo, Lindsey.

In: PLoS One, Vol. 8, No. 9, e74741, 06.09.2013.

Research output: Contribution to journalArticle

Lehman, JA, Hauck, PM, Gendron, JM, Batuello, CN, Eitel, JA, Albig, A, Kadakia, MP & Mayo, L 2013, 'Serdemetan Antagonizes the Mdm2-HIF1α Axis Leading to Decreased Levels of Glycolytic Enzymes', PLoS One, vol. 8, no. 9, e74741. https://doi.org/10.1371/journal.pone.0074741
Lehman JA, Hauck PM, Gendron JM, Batuello CN, Eitel JA, Albig A et al. Serdemetan Antagonizes the Mdm2-HIF1α Axis Leading to Decreased Levels of Glycolytic Enzymes. PLoS One. 2013 Sep 6;8(9). e74741. https://doi.org/10.1371/journal.pone.0074741
Lehman, Jason A. ; Hauck, Paula M. ; Gendron, Jaimie M. ; Batuello, Christopher N. ; Eitel, Jacob A. ; Albig, Allan ; Kadakia, Madhavi P. ; Mayo, Lindsey. / Serdemetan Antagonizes the Mdm2-HIF1α Axis Leading to Decreased Levels of Glycolytic Enzymes. In: PLoS One. 2013 ; Vol. 8, No. 9.
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