Using a set of p63 deletion mutants, we have identified a region and two critical lysine residues of p63, associated to human Split-Hand and Foot Malformation-4 (SHFM-4) syndrome, which are involved in the mechanism of Itch-mediated p63 degradation.
In contrast to previously reported patients with isolated split hand/foot anomaly and mutations in the DNA binding domain of Tp63, the mutation described herein induce an amino acid substitution (R97C) in the canonical transactivation (TA) domain.