Structural Basis of Merlin Tumor Suppressor Functions in Neurofibromatosis-2

摘要: Abstract : The development of effective and safe therapeutics that can be used to combat the debilitating incurable malignancies are associated with neurofibromatosis type II (NF2) clearly requires a detailed understanding underlying molecular basis this disease. NF2 is gene encodes cytoskeletal tumor suppressor protein merlin, which required for stabilization cell-cell contacts mediated by specialized cell surface structures called adherens junctions. Lossof- function mutations merlin hallmark NF2, these disable its functions in controlling junctions, provoking uncontrolled growth leading ultimately lethal tumors, including schwannoma, meningioma, mesothelioma. This award allowed us perform series structural biochemical studies provide foundation developing small molecule therapeutic agents bind reactivate activity mutated merlin.