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Nucleoporin Nup155 is part of the p53 network in liver cancer.
- Source :
-
Nature communications [Nat Commun] 2019 May 14; Vol. 10 (1), pp. 2147. Date of Electronic Publication: 2019 May 14. - Publication Year :
- 2019
-
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.
- Subjects :
- Animals
Carcinoma, Hepatocellular genetics
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p21 metabolism
Datasets as Topic
Gene Expression Regulation, Neoplastic
Humans
Liver Neoplasms genetics
Liver Neoplasms, Experimental genetics
Liver Neoplasms, Experimental pathology
Methyltransferases metabolism
Mice
Nuclear Pore Complex Proteins genetics
Nuclear Proteins metabolism
RNA, Small Interfering metabolism
Carcinoma, Hepatocellular pathology
Cyclin-Dependent Kinase Inhibitor p21 genetics
Liver Neoplasms pathology
Methyltransferases genetics
Nuclear Pore Complex Proteins metabolism
Nuclear Proteins genetics
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31089132
- Full Text :
- https://doi.org/10.1038/s41467-019-10133-z