1.C.110.1.1
The PNC-37 (32 aas) pore-forming peptide derived from the Mdm-2 binding domain of the p53 tumor-supressor protein which is selectively cytotoxic to cancer cells.  The 3-d structure is known from NMR analyses (Sookraj et al. 2010). PNC-37 binds to HDM-2 in a 1:1 stoichiometry to induce pore-formation, and the pores are lined by PNC-37 bound to HDM-2 at the membrane surface with the PNC-37 leader sequence lining the pores (Sarafraz-Yazdi et al. 2022). The interaction of the C-terminal domain of Vaccinia-Related Kinase 2A (VRK2A) with the B-cell lymphoma-extra Large (Bcl-xL) plays an anti-apoptotic role in cancer (Puja et al. 2023). P53 is a multifunctional protein implicated in the regulation of diverse cellular processes via transcription-dependent and transcription-independent mechanisms (Wang et al. 2024). Mitochondria maintain cellular function, and mitochondrial defects or impairment are primary causes of dopaminergic neuron degeneration in PD. Mitochondrial dysfunction-associated dopaminergic neuron degeneration is tightly regulated by p53 in PD pathogenesis. Neurodegenerative stress triggers p53 activation, which induces mitochondrial changes, including transmembrane permeability, reactive oxygen species production, Ca²⁺ overload, electron transport chain defects and other dynamic alterations, and these changes contribute to neurodegeneration and are linked closely with PD occurrence and development. P53 inhibition has been shown to attenuate mitochondrial dysfunction and protect dopaminergic neurons from degeneration under conditions of neurodegenerative stress (Wang et al. 2024).