p53 is a homotetrameric, tumor suppressor protein involved in transcriptional control of genes that regulate cell proliferation and death. In order to investigate the role that oligomerization plays in this capacity, the malleability of the sequence-structure relationship as it pertains to the quaternary structure, stability and oligomeric status of p53 is examined. This is achieved through scrutinizing the impact of two cancer-causing germline mutations found within the oligomerization domain and the analysis of hydrophobic to hydrophilic, single and double point mutations at the dimer-dimer interface, culminating in the design and structural characterization of a dimeric form of p53 by NMR. These studies produced a set of biophysically characterized p53 mutants with altered oligomeric status including monomers, dimers and destabilized tetramers ideal for probing the dependence of p53 function on oligomeric status. Specifically, studies involving the two germline mutations indicate that even partial abrogation of p53 oligomerization is sufficient for accelerated tumour progression. The prospect of functional interactions amongst p53 family members, including the p53 homologs p63 and p73, via conserved oligomerization domains is also assessed. Evidence is presented to show that the oligomerization domains of p63 and p73 preferentially fold into stable homotetramers, can form weak heterotetramers, but do not hetero-oligomerize with p53.