Ran suppresses paclitaxel-induced apoptosis in human glioblastoma cells |
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Authors: | Im Sun Woo Han-Su Jang So Young Eun Hyo Jung Kim Sun Ah Ham Hye Jung Kim Jae Heun Lee Ki Churl Chang Jin-Hoi Kim Chang Woo Han Han Geuk Seo |
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Institution: | Department of Pharmacology, Gyeongsang Institute of Health Science, Gyeongsang National University School of Medicine, Jinju 660-751, South Korea. |
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Abstract: | Yeast-based functional screening of a human glioblastoma cDNA library identified ras-related nuclear protein (Ran) as a novel
suppressor of Bcl-2-associated X protein (Bax), a pro-apoptotic member of the Bcl-2 family of proteins. Yeast cells that expressed
human Ran were resistant to Bax-induced cell death. In U373MG glioblastoma cells, stable overexpression of Ran significantly
attenuated apoptotic cell death induced by the chemotherapeutic agent paclitaxel. FACS analysis demonstrated that Ran is involved
in paclitaxel-induced cell cycle arrest. Stable overexpression of Ran also markedly inhibited the phosphorylation of Bcl-2
by paclitaxel, and inhibited the translocation of Bax, the release of cytochrome c and activation of caspase-3. Paclitaxel-induced
phosphorylation of c-JUN N-terminal kinase (JNK), but not p38, extracellular signal-regulated kinase and Akt, was markedly
suppressed in U373MG cells that stably expressed Ran. These results suggest that Ran suppresses paclitaxel-induced cell death
through the downregulation of JNK-mediated signal pathways.
Im Sun Woo and Han-Su Jang contributed equally to this work. |
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Keywords: | Apoptosis Ran Paclitaxel Glioblastoma |
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