Retention of p63 in an ER-Golgi intermediate compartment depends on the presence of all three of its domains and on its ability to form oligomers

We next asked whether the lumenal domain of p63 is dispensable for the correct targeting of the protein. To this end, a chimeric construct in which the lumenal domain of p63 was replaced by that of DPPIV (PPD, p63 cytoplasmic, p63 transmembrane, DPPIV lumenal; Fig. 9 ) was created. In a related construct we linked the cytoplasmic and transmembrane domains of A24-101 to the DPPIV lumenal domain (A24-101PPD, p63 with deletion of amino acids 24-101 cyto- plasmic, p63 transmembrane, DPPIV lumenal; Fig. 9 ). When the subeellular localization of the chimeric proteins was analyzed in transfected COS cells, A24-101PPD showed the same distribution as DPPIVwt. There was strong labeling of the cell surface ( Fig. 10 f ) , but no internal staining with a p63wt pattern (Fig. 10 e) . The same was true for the PPD chimera (Fig. 10, g and h) except that the internal staining pattern included more ER staining in addition to the Golgi and cell surface staining predominantly found for DPPIVwt and A24-101PPD. These data demonstrate that the presence of the lumenal domain of the p63 molecule is essential for the correct localization of the protein.