In addition to p53 itself, the p53 tumor suppressor family is also made up of tumor protein 63 and tumor protein p73. Like p53, p63 functions as a transcription factor to regulate the cell cycle. Mutant TP63 is also related to many cancers. In contrast, mutant p73 or a lack p73 altogether apparently does not affect tumor growth. p73 is rarely mutated in cancers. This family of tumor suppressors is found in multicellular organisms and has been shown to have a highly conserved domain structure in many species of vertebrates.
p63 and p73 were both discovered several years after the initial discovery of p53 and were classified in the p53 family due to their structural similarities. Although p53 was the first protein in the family to be discovered, certain evidence suggests that p63 was actually the original protein from which p53 and p73 evolved.
Additionally, they all have a transactivation domain located in the N–terminus, which is linked to the DNA–binding domain, followed by an oligomerization domain, and finally a C–terminus containing NLS and NES(Belyi and Levine, 2009). It appears that the highest region of conservation between the three proteins is the DNA–binding domain, sharing 55–87% homology in humans (Belyi and Levine, 2009).
The p53 family has been evolving for over one billion years. The family originated from a p63/p73 ancestor gene which is still commonly found in all invertebrates (Belyi et al. 2010). The first p53 gene was born when it split from its ancestor via a gene duplication in a cartilaginous fish, creating a p53 gene and a separate p63/p73 ancestor gene (Belyi et al. 2010). p63 and p73 then diverged from their common ancestor with a second duplication in species of bony fish (Belyi et al 2010).
Although the respective structures and functions vary between different species of vertebrates and invertebrates, the p53 family has managed to maintain its original structure and function since it began divergence (Belyi et al. 2010).
- TP63 Wikipedia page
- TP73 Wikipedia page
- p53 p63 p73 family Wikipedia page
- The p53 website
- Belyi, Vladimir A., Prashanth Ak, Elke Markert, et al. (2010). The Origins and Evolution of the P53 Family of Genes. Cold Spring Harbor Perspectives in Biology, 2(6).
- Belyi, Vladimir A., and Arnold J. Levine. (2009). One Billion Years of P53/p63/p73 Evolution. Proceedings of the National Academy of Sciences 106(42): 17609–17610.
- 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