The role of the p53 tumor suppressor in metabolism and diabetes.
In the context of tumor suppression, p53 is an undisputedly critical protein. Functioning primarily as a transcription factor, p53 helps fend off the initiation and progression of tumors by inducing cell cycle arrest, senescence or programmed cell death (apoptosis) in cells at the earliest stages of precancerous development. Compelling evidence, however, suggests that p53 is involved in other aspects of human physiology, including metabolism. Indeed, recent studies suggest that p53 plays a significant role in the development of metabolic diseases, including diabetes, and further that p53's role in metabolism may also be consequential to tumor suppression. Here, we present a review of the literature on the role of p53 in metabolism, diabetes, pancreatic function, glucose homeostasis and insulin resistance. Additionally, we discuss the emerging role of genetic variation in the p53 pathway (single-nucleotide polymorphisms) on the impact of p53 in metabolic disease and diabetes. A better understanding of the relationship between p53, metabolism and diabetes may one day better inform the existing and prospective therapeutic strategies to combat this rapidly growing epidemic.
Department of Internal MedicineWashington University School of Medicine, St Louis, Missouri, USA patkung@wustl.edu mmurphy@wistar.org.
Che-Pei
CP
Kung
Department of Internal MedicineWashington University School of Medicine, St Louis, Missouri, USA patkung@wustl.edu mmurphy@wistar.org.
Maureen E
ME
Murphy
D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D011236:Prediabetic State / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D007328:Insulin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
diabetes; insulin resistance; metabolism; p53