1. ¹Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India
2. ²Inserm U716, Pharmacologie Expérimentale, Institut Génétique Moléculaire, Hôpital St Louis and Université Paris 7, Paris, France

Correspondence: Dr S Das, Department of Microbiology and Cell Biology, Indian Institute of Science, Sir CV Raman Avenue, Malleswaram, Bangalore, Karnataka 560012, India. E-mail: sdas@mcbl.iisc.ernet.in

³Joint first author.

⁴Current address: Institute of Bioinformatics and Applied Biotechnology, Bangalore, India.

⁵Current address: Department of Clinical Molecular Biology, Graduate School of Medicine Kyoto University, Kyoto 606-8507, Japan.

Received 8 December 2008; Revised 21 April 2009; Accepted 22 April 2009; Published online 1 June 2009.

Abstract

The tumor suppressor p53 represents a paradigm for gene regulation. Its rapid induction in response to DNA damage conditions has been attributed to both increased half-life of p53 protein and also increased translation of p53 mRNA. Recent advances in our understanding of the post-transcriptional regulation of p53 include the discovery of internal ribosome entry sites (IRESs) within the p53 mRNA. These IRES elements regulate the translation of the full length as well as the N-terminally truncated isoform, p53/47. The p53/47 isoform is generated by alternative initiation at an internal AUG codon present within the p53 ORF. The aim of this review is to summarize the role of translational control mechanisms in regulating p53 functions. We discuss here in detail how diverse cellular stress pathways trigger alterations in the cap-dependent and cap-independent translation of p53 mRNA and how changes in the relative expression levels of p53 isoforms result in more differentiated p53 activity.