Yap1 as a New Therapeutic Target in Neurofibromatosis Type 2.

摘要

We hypothesized that Yap1 activity is critical for the growth- suppressing activity of Merlin, and that downmodulation of Yap1 function might constitute a novel therapeutic approach for the treatment of neurofibromatosis and other NF2-null tumors. In Aim 1, we tested whether ablation or reduction of Yap1 activity suppresses Nf2-null phenotypes in vivo. In aim 2, we attempted to identify novel proteins and small molecules that negatively regulate Yap1 activity. We have demonstrated in fact that Nf2-ablation induces YAP activity in multiple tissues in mice. We have also established a reporter system for YAP activity and have finished a genetic screen identifying kinases that might activate YAP1.