The regulation of energy metabolism and the IGF-1/mTOR pathways by the p53 protein.
In response to stress, p53 initiates the transcriptional regulation of selected target genes and various cellular responses, including cell cycle arrest, apoptosis and senescence. Recent studies revealed two additional functions of p53 in the regulation of IGF-1/AKT/mTOR pathways and energy metabolism, contributing to p53's role as a tumor suppressor. Oncogenic processes give rise to metabolic pathways focused upon the use of aerobic glycolysis (the Warburg effect) and the pentose shunt, providing higher levels of reducing activities. p53 shuts down these pathways and refocuses cells to utilize mitochondrial oxidative phosphorylation, thereby maximizing efficient ATP production and minimizing the synthesis of substrates for cell division. The use of these alternative metabolic pathways is an integral part of both normal and oncogenic phenotypes.
Feng
Zhaohui
Z
Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903, USA. fengzh@umdnj.edu
Levine
Arnold J
AJ
D000818:Animals; D004734:Energy Metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D058570:TOR Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D016159:Tumor Suppressor Protein p53; D007334:Insulin-Like Growth Factor I; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases
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