Novel Role of Merlin Tumor Suppressor in Autophagy and its Implication in Treating NF2-Associated Tumors
Annual rept. Apr 2012-31 Mar 2013
CITY OF HOPE BECKMAN RESEARCH INST DUARTE CA
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Our preliminary study demonstrated that Merlin promotes autophagy, a cellular clearance system responsible for degrading old proteins or damaged organelles within cells, and thus help mitigate the risk of tumor formation. Moreover, the cellular stress caused by loss of Merlin function was effectively suppressed by rapamycin, an autophagy-inducing compound. Therefore, we hypothesize that Merlin normally suppresses tumorigenesis in part by activating autophagy, and that this new role of Merlin in autophagy could be a target for therapeutic intervention against NF2-associated tumors. To test this hypothesis, we have evaluated the interaction of Merlin with autophagy-related proteins i.e., LC3, dynein, Ulk1Atg1. We will also analyze how Merlin mutations found in NF2 patients may affect the autophagy-inducing activity of Merlin. These analyses are expected to provide new insight into the role of Merlin in autophagy and to contribute to the development of new therapeutic means against NF2.
- Medicine and Medical Research