Tumor gene expression in vitro and in vivo

Division Of Basic Sciences - Nci

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Abstract

We identified a new function for mutant KRAS, namely a key role in the export of nuclear proteins into the cytoplasm. The function lies downstream from XPO1. It is attributable to a previously unknown complex between mutant KRAS and RAN-GAP, which mediates the hydrolysis of RAN-GTP to RAN-GDP, which is involved in regulating the cytoplasmic export of nuclear proteins. This function is non-canonical in that it is independent of KRAS activities generated at the plasma membrane. These finding may have translational implications, as novel drug combinations that take advantage of this new KRAS function can cooperate with RAS inhibitors.