Fig. 2

Cartoon illustration of the evolution of the p53 mRNA structure and the co-evolution of p53 and MDM2. a Illustration of the structures of p53(box-I) in the transactivation domains (TAD) of mRNA sequences from the pre-vertebrate (ancestral) and human p53. The structure and the MDM2-interaction of the ancestral p53 mRNA is temperature dependent and its binding to the ancestral MDM2/X is optimal at 18 °C (temperature of the natural environment of C.intestinalis) while the human homologues (MDM2 via MDMX) positively interact on either 18 °C and 30 °C temperatures. b Co-evolutionary pressure of the box-I motif of the transactivation (TA) domain of p53 and the p53 binding site on MDM family, at the RNA and protein levels. (i) RNA level: Ancestral MDM2/X interacts with the p53 mRNA in a temperature- dependent fashion while the in MDM2 requires the employment of MDMX and the activity of a p53 signaling pathway, responding to DNA damage response. (ii) Protein level: The p53 - MDM2 protein - protein interaction has evolved by changes in the flanking sequence (FS) of box-I and it is intimately related to the evolution of the p53 activity as a tumor suppressor