Figure 4

Tetramerization model of the p63/p73 interaction. (a) Heterotetramerization between p63 and p73 isoforms is possible in tissues where both proteins are coexpressed in the same cells at the same time. Squamous cell carcinomas express high levels of ΔNp63α as well as TAp73. The proapoptotic function of TAp73 seems to be repressed by the high abundance of ΔNp63 via promoter squelching, as knockdown of ΔNp63 leads to expression of Puma/Noxa with subsequent apoptosis. In basal keratinocytes ΔNp63α is also expressed at high levels. During differentiation a short burst of p73 expression can be observed. In addition, p63/p73 colocalization can be observed in some cells of the basal layer of the epidermis and the ORS of hair follicles of mouse skin. (b) Isoforms of p63 and p73 that are available for heterotetramer formation. P73 is a constitutive tetramer; therefore, all isoforms can participate in heterotetramer formation. In contrast, inactive TAp63α is a closed dimer with a buried tetramerization domain. All other p63 isoforms either lacking the N-terminal TA domain (ΔN isoforms) or the C-terminal inhibitory domain (TID, isoforms β, γ, δ and ɛ) are tetramers and therefore can participate in heterotetramer formation