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Identification of Functions of Neurofibromin Distinct from the RASGAP Domain

机译：从RasGap结构域鉴别神经纤维瘤的功能

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We proposed to study new functions of neurofibromin in the model organism, the budding yeast, Saccharornyces cerevisiae. The design of our study is mainly to generate dominant negative mutants of neurofibromin and its yeast homologs (Iral and Ira2), induce their expression in wild type yeast and elicit an interfering phenotype. We will then screen a yeast library to identify novel interaction partners of neurofibromin. We have constructed various mutants and fragments of Iral and neurofibromin. All of them have been tested in either transient or stably integrated expression. So far we have not observed any obvious interfering phenotype in the yeast strains that we have used. We have also experienced difficulties in detecting the expression of some of the mutants. We are continuing to test more yeast strains as difference strains have variable sensitivities to these mutants. Our second methodology to search for new functions of neurofibromin is gene expression profiling. We have obtained some preliminary data comparing Iral/Ira2 deletion and Ras super- activation. We are working towards verifying these data and hopefully reaching some definitive answers in the near future.

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