p53 and the regulation of hepatocyte apoptosis: implications for disease pathogenesis.
The interplay between p53 and apoptosis in diseases such as cancer, neurodegeneration, ischemia and atherosclerosis underscores the need to understand the complexity of p53 networks. Here, we highlight recent studies of p53-induced apoptosis in human diseases, with a focus on the modulation of liver cell apoptosis. In addition, recent work has provided new insights into mechanisms underlying the antiapoptotic functions of the endogenous bile acid ursodeoxycholic acid (UDCA), suggesting that the finely tuned, complex control of p53 by Mdm2 is a key step in the UDCA modulation of deregulated, p53-triggered apoptosis. The effect of targeting cell death signaling proteins has been established in preclinical models of human diseases. Finally, we review recent therapeutic strategies and clinical applications of targeted agents, with a particular emphasis on the potential use of UDCA.
Amaral
Joana D
JD
Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
Castro
Rui E
RE
Steer
Clifford J
CJ
Rodrigues
Cecília M P
CM
D017209:Apoptosis; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014580:Ursodeoxycholic Acid / Q000502:physiology
D016159:Tumor Suppressor Protein p53; D014580:Ursodeoxycholic Acid