Fig. 8. Illustration of PCNXL2 regulating the Notch signaling pathway. PCNXL2 present in the ER membrane releases a protein consisting of up of 1054 amino acids containing domain A and the pcx domain. The pcx domain exhibits ATPase activity coupled to transmembrane movement of ions (protons) by establishing a membrane potential for essential biological processes, such as liberation of the activated protein NICD from receptors. Domain A exhibits nuclear transport activity; it transports NICD from the cytoplasm to the nucleus to transcriptional factor CSL to activate the expression of Notch targeted tumor suppressor genes and to downregulate tumor oncogenes, including p21, p53, p27, Smad, p63, p65, as well as WNT signaling and AP1\HPV\MRCKα.