engleski

Importin 7 and exportin 1 link c-Myc and p53 to regulation of ribosomal biogenesis

Members of the β-karyopherin family mediate nuclear import of ribosomal proteins and export of ribosomal subunits, required for ribosome biogenesis. We report that transcription of the genes encoding the β-karyopherins importin 7 (IPO7) and exportin 1 (XPO1) and several additional proteins involved in nuclear import, is regulated positively by c-Myc and negatively by p53. Partial depletion of IPO7 leads to 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.

ribosome biogenesis; p53; c-Myc

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