Glycolytic enzymes can modulate cellular life span

Hiroshi Kondoh, Matilde E. Lleonart, Jesus Gil, Jing Wang, Paolo Degan, Gordon Peters, Dolores Martinez, Amancio Carnero, David Beach

Research output: Contribution to journalArticle

454 Scopus citations

Abstract

An unbiased screen for genes that can immortalize mouse embryonic fibroblasts identified the glycolytic enzyme phosphoglycerate mutase (PGM). A 2-fold increase in PGM activity enhances glycolytic flux, allows indefinite proliferation, and renders cells resistant to ras-induced arrest. Glucosephosphate isomerase, another glycolytic enzyme, displays similar activity and, conversely, depletion of PGM or glucosephosphate isomerase with short interfering RNA triggers premature senescence. Immortalized mouse embryonic fibroblasts and mouse embryonic stem cells display higher glycolytic flux and more resistance to oxidative damage than senescent cells. Because wild-type p53 down-regulates PGM, mutation of p53 can facilitate immortalization via effects on PGM levels and glycolysis.

Original languageEnglish (US)
Pages (from-to)177-185
Number of pages9
JournalCancer Research
Volume65
Issue number1
StatePublished - Jan 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kondoh, H., Lleonart, M. E., Gil, J., Wang, J., Degan, P., Peters, G., Martinez, D., Carnero, A., & Beach, D. (2005). Glycolytic enzymes can modulate cellular life span. Cancer Research, 65(1), 177-185.