Inhibition of Ubc9-Induced CRMP2 SUMOylation Disrupts Glioblastoma Cell Proliferation

Glioblastoma (GBM) is the most aggressive astrocytoma. Despite maximum treatment, the GBM usually recurs and the patient survival is poor. Thus, understanding the molecular mechanism of GBM progression will be meaningful to ameliorate this situation. In this study, collapsin response mediator protein 2 (CRMP2) and Ubc9 protein levels were evaluated in three GBM cell lines. Sumoylated CRMP2 were enriched and immunoprecipitated using SUMO1 and IgG antibodies. CRMP2-K374A mutant was generated by site-direct mutagenesis. All indicated constructs were transfected into GL15 cells, and the corresponding proliferation-promoting effect was assessed through cell proliferation ratio. The t-CSM peptide was used to disturb Ubc9-CRMP2 interaction. CRMP2 is expressed in all tested GBM cell lines. The Ubc9 protein levels are positively correlated with CRMP2 level, and both can promote GBM cell proliferation. Blocking CRMP2 SUMOylation through SUMOylation-incompetent mutant or small peptide suppresses CRMP2-induced GBM cell proliferation. This study demonstrates that the CRMP2 SUMOylation exists widely in GBM cells and drives glioblastoma proliferation. CRMP2 SUMOylation inhibition can significantly suppress GBM proliferation in vitro.