title: Importin 7 and exportin 1 link c-Myc and p53 to regulation of ribosomal biogenesis.
abstract: Members of the β-karyopherin family mediate nuclear import of ribosomal proteins and export of ribosomal subunits, both required for ribosome biogenesis. We report that transcription of the β-karyopherin genes importin 7 (IPO7) and exportin 1 (XPO1), and several additional nuclear import receptors, is regulated positively by c-Myc and negatively by p53. Partial IPO7 depletion triggers p53 activation and p53-dependent growth arrest. Activation of p53 by IPO7 knockdown has distinct features of ribosomal biogenesis stress, with increased binding of Mdm2 to ribosomal proteins L5 and L11 (RPL5 and RPL11). Furthermore, p53 activation is dependent on RPL5 and RPL11. Of note, IPO7 and XPO1 are frequently overexpressed in cancer. Altogether, we propose that c-Myc and p53 counter each other in the regulation of elements within the nuclear transport machinery, thereby exerting opposing effects on the rate of ribosome biogenesis. Perturbation of this balance may play a significant role in promoting cancer.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Golomb
authors.forename: Debora Rosa
authors.initials: DR
authors.lastname: Bublik
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wilder
authors.forename: Reinat
authors.initials: R
authors.lastname: Nevo
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kiss
authors.forename: Kristina
authors.initials: K
authors.lastname: Grabusic
authors.forename: Sinisa
authors.initials: S
authors.lastname: Volarevic
authors.forename: Moshe
authors.initials: M
authors.lastname: Oren
mesh_terms: D021581:Active Transport, Cell Nucleus; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012269:Ribosomal Proteins / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000097606:Exportin 1 Protein
chemical_list: D028884:Karyopherins; D016271:Proto-Oncogene Proteins c-myc; D018160:Receptors, Cytoplasmic and Nuclear; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; D000097606:Exportin 1 Protein; C466996:IPO7 protein, human; C489427:MYC protein, human; C056368:ribosomal protein L4