Introduction

To be or not to be a cancer? It seem cells expressing the tumor protein 73 (p73) agonize whether to induce apoptosis upon oncogenic stress — although its knockout does not lead to formation of cancer in mice. 

While its sister protein p53 is mutated in multiple cancers, tumour suppressor function of p73 is still under debate. Understanding how it regulates anti-cancer gene expression, therefore, may indicate the implications and functional significance of p73 in cancer.

As a transcription factor, p73 binds RE to regulate transcription of downstream genes. Here, loop-sheet-helix motif of its DNA binding domain (DBD) forms favorable electrostatic interactions with the DNA backbone (Figure 1), where an octahedrally coordinated zinc ion aids binding and may also be required for proper folding.

Figure 1. The surface charge interaction between p73 DBD tetramers and RE

Interestingly, the activity of this tetrameric protein is determined by sequence of its target DNA; the length of spacer between Response Elements (RE) is suggested to influence its oligomerization state and structural organization, which then alters its transactivation activity.

Figure 2. The octahedral coordination of zinc ion by residues in p73 DBD