Novel Role of Merlin Tumor Suppressor in Autophagy and Its Implication in Treating NF2-Associated Tumors
Technical Report,01 Apr 2011,31 Mar 2015
Beckman Research Institute of the City of Hope Duarte United States
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Neurofibromatosis type 2 NF2 is an autosomal dominant disorder characterized by the development of brain tumors of peripheral nervous system origin. We endeavored to improve understanding of NF2 pathogenesis at the genetic and molecular levels. The gene causative for NF2 has been identified as the tumor suppressor Merlin, and several mutations of Merlin found in NF2 patients have been linked to loss of growth suppressive activity of Merlin. A major goal of this project has been to elucidate novel functions of Merlin in autophagy, a cellular clearance system responsible for degrading old proteins or damaged organelles within cells, thus helping to mitigate the risk of tumor formation. We successfully confirmed the novel role of Merlin in promoting autophagy. We showed that Merlin is a part of multi protein complex that serves as a scaffolding machinery to promote autophagic membrane assembly.