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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). P53 inhibition attenuates mitochondrial dysfunction and protects dopaminergic neurons from degeneration under conditions of neurodegenerative stress,  and thus, p53 may be a potential target for neuroprotective therapy of poarkinson's disease (PD) (Wang et al. 2022).

References associated with 1.C.110 family:

Puja, R., S. Dutta, and K. Bose. (2023). Elucidating the interaction of C-terminal domain of Vaccinia-Related Kinase 2A (VRK2A) with B-cell lymphoma-extra Large (Bcl-xL) to decipher its anti-apoptotic role in cancer. Biochem. J. 480: 1871-1885. 37943248
Sarafraz-Yazdi, E., S. Mumin, D. Cheung, D. Fridman, B. Lin, L. Wong, R. Rosal, R. Rudolph, M. Frenkel, A. Thadi, W.F. Morano, W.B. Bowne, M.R. Pincus, and J. Michl. (2022). PNC-27, a Chimeric p53-Penetratin Peptide Binds to HDM-2 in a p53 Peptide-like Structure, Induces Selective Membrane-Pore Formation and Leads to Cancer Cell Lysis. Biomedicines 10:. 35625682
Sookraj, K.A., W.B. Bowne, V. Adler, E. Sarafraz-Yazdi, J. Michl, and M.R. Pincus. (2010). The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide. Cancer Chemother Pharmacol 66: 325-331. 20182728
Thadi, A., E.M. Gleeson, M. Khalili, M.F. Shaikh, E. Goldstein, W.F. Morano, L.M. Daniels, N. Grandhi, H. Glatthorn, S.D. Richard, P.M. Campbell, E. Sarafraz-Yazdi, M.R. Pincus, and W.B. Bowne. (2020). Anti-Cancer Tumor Cell Necrosis of Epithelial Ovarian Cancer Cell Lines Depends on High Expression of HDM-2 Protein in Their Membranes. Ann Clin Lab Sci 50: 611-624. 33067207
Wang, Y.F., Y.D. Wang, S. Gao, and W. Sun. (2022). Implications of p53 in mitochondrial dysfunction and Parkinson''s disease. Int J. Neurosci. 1-12. [Epub: Ahead of Print] 36514978