Role of p90(RSK) in regulating the Crabtree effect: implications for cancer.
High glucose inhibits mitochondrial respiration, known as the 'Crabtree effect', in cancer cells and possibly other cell types. The upstream pathways regulating this phenomenon are poorly understood. In diabetes, where glucose levels are elevated, the p90(RSK) (p90 ribosomal S6 kinase) has received much attention as a potential upstream mediator of the effects of high glucose. Evidence is also emerging that p90(RSK) may play a role in cancer cell signalling, although the role of p90(RSK) in regulating cancer cell metabolism is unclear. In the present paper, we provide an overview of the Crabtree effect and its relationship to mitochondrial metabolism. Furthermore, preliminary data are presented suggesting a role for p90(RSK) and its upstream components, the ERK (extracellular-signal-regulated kinase) family of MAPKs (mitogen-activated protein kinases), in the Crabtree effect.
School of Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Emily K
EK
Redman
Paul S
PS
Brookes
Marcin K
MK
Karcz
D002460:Cell Line; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
D038744:Ribosomal Protein S6 Kinases, 90-kDa