title: Identification of a new CRMP5 isoform present in the nucleus of cancer cells and enhancing their proliferation.
abstract: Collapsin Response Mediator Protein 5 (CRMP5) belongs to a family of five cytosolic proteins highly expressed in the developing nervous system but downregulated in the adult brain. When expressed at the adult stage, CRMP5 is involved in neurological disorders. Indeed, CRMP5 is found expressed in cancer cells of some brain tumors, such as glioblastoma, or in small cell lung cancer causing paraneoplastic neurological syndromes as a result of cancer-induced auto-immune processes. Nevertheless, its role in cancer pathology is still obscure. Here, we show a new short isoform, derived from C-terminal processing of CRMP5, presenting a nuclear localization both in human glioblastoma, and in cancer cell lines (H69, GL15). By mutational analysis, we demonstrate that nuclear translocation occurs via nuclear localization signal (NLS), where the essential residue for nuclear location is K391. Direct CRMP5/ tubulin interaction, previously shown during brain development, does not occur for cytosolic CRMP5 in pathological conditions, leading to the suggestion that in cancer cells CRMP5 is not sequestered in the cytosol; therefore it may undergo C-terminal truncation allowing the exposure of the NLS for active translocation. Moreover, we show that the function associated with the CRMP5 nuclear targeting is an increase of cell proliferation activity.
authors.affiliation: INSERM, UMR-S1028, CNRS, UMR-5292, Lyon Neuroscience Research Center, Neuro-Oncology and Neuro-Inflammation Team, 7, Rue Guillaume Paradin, Lyon Cedex 08 F-69372, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Brot
authors.forename: Céline
authors.initials: C
authors.lastname: Malleval
authors.forename: Claire
authors.initials: C
authors.lastname: Benetollo
authors.forename: Carole
authors.initials: C
authors.lastname: Auger
authors.forename: David
authors.initials: D
authors.lastname: Meyronet
authors.forename: Véronique
authors.initials: V
authors.lastname: Rogemond
authors.forename: Jérôme
authors.initials: J
authors.lastname: Honnorat
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Moradi-Améli
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004261:DNA Replication; D005434:Flow Cytometry; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D006867:Hydrolases; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019913:Nuclear Localization Signals / Q000378:metabolism*; D020033:Protein Isoforms; D011817:Rabbits; D014183:Transplantation, Heterologous; D014404:Tubulin / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D019913:Nuclear Localization Signals; D020033:Protein Isoforms; D014404:Tubulin; C415087:DPYSL5 protein, human; D006867:Hydrolases