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 D. Mayo

Research output: Contribution to journalArticle

6 Scopus citations

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 (US)
Article numbere74741
JournalPloS one
Volume8
Issue number9
DOIs
StatePublished - Sep 6 2013

ASJC Scopus subject areas

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

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    Lehman, J. A., Hauck, P. M., Gendron, J. M., Batuello, C. N., Eitel, J. A., Albig, A., Kadakia, M. P., & Mayo, L. D. (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