1.C.110 The Pore-forming PNC-27 Peptide of 32 aas from the p53 Tumor Suppressor Protein (PNC-27) Family

The 32 amino acid PNC-27 peptide (PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG) inserts into the membranes of tumor cells and selectively kills them, leaving normal cells unaffected.  This peptide is from the Mdm-2 binding domain of the p53 protein which is selectively cytotoxic to cancer cells.  The NMR structure is available (PDB# 1Q2F; 12QI-A).  The p53 cellular tumor antigen, p53-TAD, is 393 aas in humans and of similar sizes in other animals (Sookraj et al. 2010). Anti-cancer tumor cell necrosis of epithelial ovarian cancer cell lines depends on high expression of the HDM-2 protein in their membranes (Thadi et al. 2020). The HDM-2 protein is highly expressed in the membranes of ovarian cancer cell lines and colocalizes with PNC-27. Thus, the association of PNC-27 with preferentially expressed membrane HDM-2 isoforms results in a model for the formation of transmembrane pores and epithelial ovarian cancer tumor cell necrosis (Thadi et al. 2020).