Kondoh Hiroshi, Lleonart Matilde E, Gil Jesus, Wang Jing, Degan Paolo, Peters Gordon, Martinez Dolores, Carnero Amancio, Beach David
Wolfson Institute for Biomedical Research, University College London, London Research Institute, London, United Kingdom.
Cancer Res. 2005 Jan 1;65(1):177-85.
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.
一项针对能够使小鼠胚胎成纤维细胞永生化的基因进行的无偏筛选鉴定出了糖酵解酶磷酸甘油酸变位酶（PGM）。PGM活性增加2倍可增强糖酵解通量，使细胞能够无限增殖，并使细胞对ras诱导的生长停滞产生抗性。另一种糖酵解酶葡萄糖磷酸异构酶也表现出类似活性，相反，用短发夹RNA耗尽PGM或葡萄糖磷酸异构酶会引发早衰。永生化的小鼠胚胎成纤维细胞和小鼠胚胎干细胞比衰老细胞表现出更高的糖酵解通量和更强的抗氧化损伤能力。由于野生型p53会下调PGM，p53的突变可通过影响PGM水平和糖酵解促进细胞永生化。
