Alterations of the nuclear transport system in hepatocellular carcinoma – New basis for therapeutic strategies  Martin Beck, Peter Schirmacher, Stephan Singer  Journal of Hepatology  Volume 67, Issue 5, Pages 1051-1061 (November 2017) DOI: 10.1016/j.jhep.2017.06.021 Copyright © 2017 Terms and Conditions

Fig. 1 The nuclear transport system. (A left panel) The nuclear pore complex (NPC) is embedded in the nuclear envelope and includes the indicated subcomplexes: cytoplasmic filaments, cytoplasmic ring, nuclear ring, inner pore ring, and nuclear basket. (A right panel) The subcomplexes are composed of subsets of nucleoporins (NUPs) indicated as colour-coded boxes: Y-complexes in dark yellow and dark purple; the inner ring complex in light blue; the transmembrane NUPs in orange; the NUP62 complex in green; cytoplasmic complexes in light yellow; and nuclear basket complexes are in light purple. (B) List of nuclear transport receptors (NTRs) sorted based on their transport directionality (import=blue, export=red, bi-directional=bold). (C) NTR-dependent import pathway either with a heterotrimeric complex containing Importin-β, Importin-α and a cargo protein with a nuclear localization signal (NLS) or a heterodimeric complex containing Importin-β and a cargo protein with a NLS. Upon binding to Ran-GTP within the nucleus each of the complexes dissociate. Export pathway with a trimeric complex containing Ran-GTP, exportin-1 (XPO1/CRM1) and a cargo protein with a nuclear export signal. Upon conversion of Ran-GTP to Ran-GDP the complex dissociates in the cytoplasm. Also shown re-shuttling of Importin-α by exportin-2 (XPO2/CAS) together with Ran-GTP and of Importin-β by Ran-GTP alone from the nucleus to the cytoplasm. IPO, Importin; KPNA, Karyopherin alpha; KPNB, Karyopherin beta; NES, nuclear export signal; TNPO, Transportin. Journal of Hepatology 2017 67, 1051-1061DOI: (10.1016/j.jhep.2017.06.021) Copyright © 2017 Terms and Conditions

Fig. 2 Levels at which members of the nuclear transport system (NTRs and/or NUPs) can be linked to liver cancer relevant pathways. (1) import/export of transcription factors (TF) either nuclear transport receptor (NTR)-dependent (blue) or -independent (red), (2) transcriptional regulation/chromatin interaction (light blue), or (3) post-transcriptional regulation such as mRNA (wavy black lines) export/stability (light purple). Journal of Hepatology 2017 67, 1051-1061DOI: (10.1016/j.jhep.2017.06.021) Copyright © 2017 Terms and Conditions