Mitochondrial Localization and Regulation of BRAFV600E in Thyroid Cancer: A Clinically Used RAF Inhibitor Is Unable to Block the Mitochondrial Activities of BRAFV600E
作者： Min Hee Lee , Seong Eun Lee , Dong Wook Kim , Min Jeong Ryu , Sung Jin Kim
DOI: 10.1210/JC.2010-1071
关键词:
摘要: Context: The oncogenic BRAFV600E mutation results in an active structural conformation characterized by greatly elevated ERK activity. However, additional cellular effects caused subcellular action of remain to be identified. Objective: To explore these effects, differences the localization wild-type and mutant BRAF thyroid cancer were investigated. Results: A significant proportion endogenous exogenous BRAFV600E, but not BRAF, was detected mitochondrial fraction, similar other mutants including BRAFV600D, BRAFV600K, BRAFV600R, BRAFG469A, which showed kinase activity localization. Induced expression suppressed apoptotic responses against staurosporine TNFα/cycloheximide. Interestingly, antiapoptotic activities unaffected sorafenib U0126 suppression MAPK (MEK) activities. Similarly, although RAF inhibitor sora...
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