TY - JOUR AU - Holzer, Kerstin AU - Ori, Alessandro AU - Cooke, Amy AU - Dauch, Daniel AU - Drucker, Elisabeth AU - Riemenschneider, Philip AU - Andres-Pons, Amparo AU - DiGuilio, Amanda L AU - Mackmull, Marie-Therese AU - Baßler, Jochen AU - Roessler, Stephanie AU - Breuhahn, Kai AU - Zender, Lars AU - Glavy, Joseph S AU - Dombrowski, Frank AU - Hurt, Ed AU - Schirmacher, Peter AU - Beck, Martin AU - Singer, Stephan TI - Nucleoporin Nup155 is part of the p53 network in liver cancer. JO - Nature Communications VL - 10 IS - 1 SN - 2041-1723 CY - [London] PB - Nature Publishing Group UK M1 - DKFZ-2019-01244 SP - 2147 PY - 2019 AB - Cancer-relevant signalling pathways rely on bidirectional nucleocytoplasmic transport events through the nuclear pore complex (NPC). However, mechanisms by which individual NPC components (Nups) participate in the regulation of these pathways remain poorly understood. We discover by integrating large scale proteomics, polysome fractionation and a focused RNAi approach that Nup155 controls mRNA translation of p21 (CDKN1A), a key mediator of the p53 response. The underlying mechanism involves transcriptional regulation of the putative tRNA and rRNA methyltransferase FTSJ1 by Nup155. Furthermore, we observe that Nup155 and FTSJ1 are p53 repression targets and accordingly find a correlation between the p53 status, Nup155 and FTSJ1 expression in murine and human hepatocellular carcinoma. Our data suggest an unanticipated regulatory network linking translational control by and repression of a structural NPC component modulating the p53 pathway through its effectors. LB - PUB:(DE-HGF)16 C6 - pmid:31089132 C2 - pmc:PMC6517424 DO - DOI:10.1038/s41467-019-10133-z UR - https://inrepo02.dkfz.de/record/143670 ER -