Fig. 3

Merlin signaling pathways and potential therapeutic targets in NF2. A schematic depiction of the main intracellular pathways regulated by the protein product of the NF2 gene (merlin (is shown by golden)). Merlin regulates cell survival, proliferation, and cell–cell interaction in response to multiple proliferative signaling pathways at the plasma membrane and in the nucleus. Merlin can predominantly block the RTKs’ activity on their downstream targets, including RAS, PI3K, and Rac. Merlin inhibits Wnt/β-catenin signaling through inhibit translocation of β-catenin to the nucleus. At the nucleus (inhibition CRL4^DCAF1) and cell cortex (promoting MST1/2), merlin can regulate Hippo signaling pathway. As a result, the expression of target genes of YAP will decrease. Merlin may also block LIN28B in the nucleus, reducing let-7 miRNA cluster repression and downregulating proto-oncogenic proteins including MYC and RAS. Diverse treatment options have been investigated for NF2 patients, including the suppression of merlin-regulated proteins and other cellular receptors. Pathogenic mutations in NF2 patients cause merlin function loss, which modulates downstream activity in each pathway, promoting cell growth, protein and fatty acid synthesis, proliferation, and survival. The five white boxes provided are current inhibitors of this pathway with their respective targets. Proteins are also illustrated in circular shapes, and each of them has been given a distinct color. the bilayer cellular plasma membrane with phospholipid compounds is presented at the top in pink. Also, the blue area in the cell represents the nucleus and the two blue straight lines within, represent genes involved in this pathway. Black arrows indicate the act of promotion and blocking lines indicate the act of suppression