Ran suppresses paclitaxel-induced apoptosis in human glioblastoma cells

• Published in: Apoptosis (London) Vol. 13; no. 10; pp. 1223 - 1231
• Main Authors: Woo, Im Sun, Jang, Han-Su, Eun, So Young, Kim, Hyo Jung, Ham, Sun Ah, Kim, Hye Jung, Lee, Jae Heun, Chang, Ki Churl, Kim, Jin-Hoi, Han, Chang Woo, Seo, Han Geuk
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01-10-2008; Springer US; Springer Nature B.V
• Subjects: Apoptosis - drug effects; Apoptosis Regulatory Proteins - metabolism; bcl-2-Associated X Protein - metabolism; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Biology; Cell Line, Tumor; Enzyme Activation - drug effects; G1 Phase - drug effects; Gene Library; Glioblastoma - enzymology; Glioblastoma - pathology; Humans; JNK Mitogen-Activated Protein Kinases - metabolism; Models, Biological; Mortality; Oncology; Original Paper; Paclitaxel - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; ran GTP-Binding Protein - metabolism; Reactive Oxygen Species - metabolism; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - drug effects; Translocation; Virology; Yeasts; Ran; Paclitaxel; Glioblastoma; Apoptosis
• ISSN: 1360-8185; 1573-675X
• DOI: 10.1007/s10495-008-0247-0

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.