This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kondoh, H. Articles by Beach, D. Search for Related Content PubMed PubMed Citation Articles by Kondoh, H. Articles by Beach, D.

Glycolytic Enzymes Can Modulate Cellular Life Span

¹ Wolfson Institute for Biomedical Research, University College London and ² Cancer Research UK, London Research Institute, London, United Kingdom; ³ Mutagenesis Laboratory, National Cancer Research Institute-Genova, Genoa, Italy; and ⁴ Experimental Therapeutics Program, Centro Nacional de Investigaciones, Oncologicas, Madrid, Spain

Requests for reprints: Hiroshi Kondoh, Cancer Research UK, London Research Institute, London, United Kingdom. Phone: 44-020-7269-3594; Fax: 44-020-7269-3094; E-mail: hiroshi.kondoh{at}cancer.org.uk.

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.

Key Words: Phosphoglycerate mutase • glycolysis • senescence • the Warburg effect • oxidative stress

This article has been cited by other articles:

				T. Funasaka, H. Hu, V. Hogan, and A. Raz Down-regulation of Phosphoglucose Isomerase/Autocrine Motility Factor Expression Sensitizes Human Fibrosarcoma Cells to Oxidative Stress Leading to Cellular Senescence J. Biol. Chem., December 14, 2007; 282(50): 36362 - 36369. [Abstract] [Full Text] [PDF]

				J.-w. Kim and C. V. Dang Cancer's Molecular Sweet Tooth and the Warburg Effect. Cancer Res., September 15, 2006; 66(18): 8927 - 8930. [Abstract] [Full Text] [PDF]

				T. Sakamaki, M. C. Casimiro, X. Ju, A. A. Quong, S. Katiyar, M. Liu, X. Jiao, A. Li, X. Zhang, Y. Lu, et al. Cyclin d1 determines mitochondrial function in vivo. Mol. Cell. Biol., July 1, 2006; 26(14): 5449 - 5469. [Abstract] [Full Text] [PDF]

				S. Matoba, J.-G. Kang, W. D. Patino, A. Wragg, M. Boehm, O. Gavrilova, P. J. Hurley, F. Bunz, and P. M. Hwang p53 Regulates Mitochondrial Respiration Science, June 16, 2006; 312(5780): 1650 - 1653. [Abstract] [Full Text] [PDF]

				S. Vanharanta, P. J. Pollard, H. J. Lehtonen, P. Laiho, J. Sjoberg, A. Leminen, K. Aittomaki, J. Arola, M. Kruhoffer, T. F. Orntoft, et al. Distinct expression profile in fumarate-hydratase-deficient uterine fibroids Hum. Mol. Genet., January 1, 2006; 15(1): 97 - 103. [Abstract] [Full Text] [PDF]