p53 and the regulation of hepatocyte apoptosis: implications for disease pathogenesis

Joana D. Amaral, Rui E. Castro, Clifford J. Steer, Cecília M.P. Rodrigues

Research output: Contribution to journalReview articlepeer-review

29 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)531-541
Number of pages11
JournalTrends in Molecular Medicine
Volume15
Issue number11
DOIs
StatePublished - Nov 2009

Bibliographical note

Funding Information:
Supported in part by grant PTDC/SAU-FCF/67912/2006 from Fundação para a Ciência e a Tecnologia (FCT), Lisbon, Portugal (to C.M.P.R). J.D.A. and R.E.C. are recipients of postdoctoral fellowships (SFRH/BPD/47376/2008 and SFRH/BPD/30257/2006, respectively) from FCT. The authors thank members of the laboratory for critical reading of the manuscript.

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