Ran Binding Protein 9 (RanBP9) is a novel mediator of cellular DNA damage response in lung cancer cells

• DOI: 10.18632/oncotarget.7813
• Publication Date: 2016-03-01T10:33:09Z
• Authors: Dario Palmieri; Mario Scarpa; Anna Tessari; Rexhep Uka; Foued Amari; Cindy Lee; Timothy Richmond; Claudia Foray; Tyler Sheetz; Ashley Braddom; Christin E. Burd; Jeffrey D. Parvin; Thomas Ludwig; Carlo M. Croce; Vincenzo Coppola
• Keywords: Nuclear export signal

// Dario Palmieri 1, 2 , Mario Scarpa Anna Tessari 1 Rexhep Uka Foued Amari Cindy Lee Timothy Richmond Claudia Foray Tyler Sheetz Ashley Braddom Christin E. Burd Jeffrey D. Parvin Thomas Ludwig Carlo M. Croce Vincenzo Coppola Department of Molecular Virology, Immunology and Medical Genetics, College Medicine, 43210 Columbus, OH, USA Solid Tumor Biology Program, Comprehensive Cancer Center, The Ohio State University, Correspondence to: Coppola, e-mail: [e-mail] Keywords: RanBP9, RanBPM, ATM, DNA damage, ionizing radiation Received: December 09, 2015      Accepted: January 29, 2016      Published: March 01, 2016 ABSTRACT Ran Binding Protein 9 (RanBP9, also known as RanBPM) is an evolutionary conserved scaffold protein present both in the nucleus cytoplasm cells whose biological functions remain elusive. We show that active ATM phosphorylates RanBP9 on at least two different residues (S181 S603). In response to IR, rapidly accumulates into lung cancer cells, but this nuclear accumulation prevented by inhibition. stable silencing three cell lines significantly affects Damage Response (DDR), resulting delayed activation key components cellular IR such itself, Chk2, γH2AX, p53. Accordingly, abrogation expression reduces homologous recombination-dependent repair efficiency, causing abnormal IR-induced senescence apoptosis. summary, here we report a novel mediator DDR, upon dependent kinase activity. absence hampers molecular mechanisms leading efficient damaged DNA, enhanced sensitivity genotoxic stress. These findings suggest targeting might enhance anti-neoplastic treatment.