Interactions of mutant p53 with DNA: guilt by association

Since the very early days of p53 research, the gain of oncogenic activities by some mutant p53 proteins had been suspected as an important factor contributing to cancer progression. Considerable progress towards understanding the biology of mutant p53 has been made during the last years, the quintessence being the realization that the impact of mutant p53 proteins on the transcriptome of a tumor cell is much more global than previously thought. The emerging role of mutant p53 proteins in coordinating oncogenic signaling and chromatin modifying activities reveals an until now unsuspected function of these proteins as important modifiers of the oncogenic transcriptional response. Notwithstanding the fact that the sequence specific DNA binding activity of mutant p53 proteins is impaired, they are still able to associate with specific loci on DNA by utilizing different mechanisms. The ability to associate with DNA appears to be crucial for the master role of mutant p53 proteins in coordinating oncogenic transcriptional responses.