title: Transportin 2 regulates apoptosis through the RNA-binding protein HuR.
abstract: In response to severe stress, apoptotic cell death is engaged. Apoptosis is a well orchestrated process that involves the activation and implication of many factors. In this study, we identified a role for the nuclear trafficking factor TRN2 (transportin 2) in cell death. TRN2 is normally responsible for the nuclear import of the RNA-binding protein HuR. During apoptosis, however, HuR accumulates in the cytoplasm. This is due to the caspase-mediated cleavage of the cytoplasmic fraction of HuR. One of the cleavage fragments generated by this processing of HuR interacts with TRN2 and thus blocks the re-import of HuR into the nucleus. This concentrates HuR in the cytoplasm, advancing apoptosis. Therefore, increasing or decreasing the levels of TRN2 has an inverse consequential effect on cell death, demonstrating for the first time the role of a nucleocytoplasmic transport factor in apoptosis.
authors.affiliation: Department of Biochemistry and Rosalind and Morris Goodman Cancer Center, McGill University, Montreal, Quebec, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: von Roretz
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Macri
authors.forename: Imed-Eddine
authors.initials: IE
authors.lastname: Gallouzi
mesh_terms: D017209:Apoptosis; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D028961:beta Karyopherins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C503621:TNPO2 protein, human; D028961:beta Karyopherins