Conclusion

In a broader context, p73 belongs to and shares conserved DNA recognition motif of the well-known p53 protein family (Figure 7) which regulate DNA repair proteins. However, its activity is more sensitive to spacer length. Also, its smaller dimerization and tetramerization interfaces result in lower DNA binding affinity.

After all, a shorter spacer length between RE half-sites ultimately decreases transcriptional activity of p73, by affecting its oligomerization state, DBD quaternary structure and DNA conformation of itself. Accordingly, an insertional mutation in RE spacer may affect p73 transactivation, potentially resulting in a tumourigenic phenotype as there would be reduced expression of DNA repair proteins.

As only isolated DBD are used in these experiments, additional studies with the whole p73 tetramer would further reveal the relevant interactions and function of N- and C-term domains, giving a complete mechanism of p73 transactivation regulation.




Figure 7: This is a BLAST local alignment of p53 and p73 proteins, this alignment shows there is 51% sequence identity. An E value of 2x10-89 shows it is unlikely the alignment occurred by chance, suggesting DBD is highly conserved.