Nucleoporin Nup155 is part of the p53 network in liver cancer.
Animals
Carcinoma, Hepatocellular
/ genetics
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p21
/ genetics
Datasets as Topic
Gene Expression Regulation, Neoplastic
Humans
Liver Neoplasms
/ genetics
Liver Neoplasms, Experimental
/ genetics
Methyltransferases
/ genetics
Mice
Nuclear Pore Complex Proteins
/ genetics
Nuclear Proteins
/ genetics
RNA, Small Interfering
/ metabolism
Tumor Suppressor Protein p53
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 05 2019
14 05 2019
Historique:
received:
14
01
2018
accepted:
16
04
2019
entrez:
16
5
2019
pubmed:
16
5
2019
medline:
2
7
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31089132
doi: 10.1038/s41467-019-10133-z
pii: 10.1038/s41467-019-10133-z
pmc: PMC6517424
doi:
Substances chimiques
CDKN1A protein, human
0
Cyclin-Dependent Kinase Inhibitor p21
0
NUP155 protein, human
0
NUP155 protein, mouse
0
Nuclear Pore Complex Proteins
0
Nuclear Proteins
0
RNA, Small Interfering
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
FTSJ1 protein, human
EC 2.1.1.-
Methyltransferases
EC 2.1.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2147Subventions
Organisme : NIGMS NIH HHS
ID : R15 GM119118
Pays : United States
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : TRR/SF209 (B04)
Pays : International
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : Si1487/3-1
Pays : International
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