Nucleoporin Nup155 is part of the p53 network in liver cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31089132.
- Also identified by DOI 10.1038/s41467-019-10133-z and PMC identifier 6517424.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Carcinoma, Hepatocellular
- Cyclin-Dependent Kinase Inhibitor p21
- Liver Neoplasms
- Methyltransferases
- Nuclear Pore Complex Proteins
- Nuclear Proteins
- Tumor Suppressor Protein p53