The interferon-induced GTPase, mGBP-2, confers resistance to paclitaxel-induced cytotoxicity without inhibiting multinucleation.

Interferon (IFN) exposure promotes a wide variety of cellular changes, many of which are still poorly characterized. Many of these changes are initiated through the induction or repression of hundreds of genes. One multigene family of GTPases induced by both type I and type II IFNs is the Guanylate Binding Protein (GBP) family. In this study we show that a murine GBP, mGBP-2, confers resistance to a microtubule-stabilizing drug used in cancer therapy, paclitaxel. Paclitaxel-treated, mGBP-2-expressing NIH 3T3 cells showed less rounding and substrate detachment than treated control cells. mGBP-2 also conferred resistance to paclitaxel-induced cytotoxicity at paclitaxel concentrations from 0.005 to 15 microM. mGBP-2-mediated paclitaxel resistance did not protect against the generation of multinucleate cells but fewer of these cells progressed to apoptosis.