Importin 7 and Exportin 1 Link C-Myc and P53 to Regulation of Ribosomal Biogenesis

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2012 Jan 31

PMID 22284678

Citations 77

Authors

Lior Golomb

Debora Rosa Bublik

Sylvia Wilder

Reinat Nevo

Vladimir Kiss

Kristina Grabusic

Sinisa Volarevic

Moshe Oren

Affiliations

Soon will be listed here.

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.

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