The p53 protein is encoded by the TP53 gene (20 kb) located on the p arm of chromosome 17. The expression and biosynthesis of p53 is maintained in a variety of ways, including transcriptional and translational control, alternative splicing, and more (Terzian and Lozano, 2010).
p53 synthesis can be activated in response to DNA damage. Recent studies have shwon that the amount of TP53 mRNA itself does not change in response to stress signals; instead, there are several factors affecting the rate of translation initiation (Ponnuswamy and Fahraeus 2012). Translation initiation is usually initiated around the 5'UTR cap of the mRNA. This recruits several initiation factors, forming a pre-initiation complex. This pre-initiation complex scans the mRNA for the initiation codon, where the 60S ribosomal subunit is recruited to begin translation. Several steps in this process are subject to regulation.
In normal, unstressed cells, p53 production is regulated primarily by the binding of MDM2, which targets p53 for degradation (Thierry 1994). MDM2 is an E3 ubiquitin ligase that negatively regulates p53 by directly blocking p53 transcriptional activity and mediating p53 degradation. p53 activates the transcription of the mdm2 gene, while MDM2 binds p53 and inhibits its ability to function properly (Wu et al. 1993). This forms an autoregulatory feedback loop in which MDM2 is able to control the production and activity of p53. In response to a stress signal, MDM2 degrades itself via polyubiquitylation, which lengthens the half-life of p53 and leads to an accumulation of p53 in the cell (Riley et al. 2008).
- Ponnuswamy, A, and R Fahraeus. (2012).The regulation of p53 synthesis . Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti, 25(2): 2S32–37.
- Riley, Todd, Eduardo Sontag, Patricia Chen, and Arnold Levine. (2008). Transcriptional control of human p53-regulated genes. Nature Reviews Molecular Cell Biology, 9(5): 402–412.
- Terzian, Tamara, and Guillermina Lozano. (2010). Building p53. Genes & Development, 24(20): 2229–2232.
- Thierry Soussi. (1994). P53 Information. The TP53 Web Site. Retrieved 17 February 2014.
- Wu, X, J H Bayle, D Olson, and A J Levine. (1993). The p53-mdm-2 autoregulatory feedback loop . Genes & Development, 7(7A): 1126–1132.
- Keri: p53: Introduction
- Keri: p53: Biological function
- Keri: p53: Biosynthesis
- Keri: p53: Gene sequence
- Keri: p53: Amino acid sequence and composition
- Keri: p53: Secondary and tertiary structure
- Keri: p53: Domains and structural motifs
- Keri: p53: Interactions with macromolecules and small molecules
- Keri: p53: Molecular biodiversity and evolution
- Keri: p53: Literature overview
- Keri: p53: Useful online resources