p53 mRNA and p53 Protein Structures Have Evolved Independently to Interact with MDM2
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26823446
DOI
10.1093/molbev/msw012
PII: msw012
Knihovny.cz E-resources
- Keywords
- Ciona intestinalis, MDM2, RNA structures, invertebrate., p53, protein–RNA interactions,
- MeSH
- Apoptosis genetics MeSH
- Ciona intestinalis MeSH
- DNA Primers MeSH
- RNA, Messenger genetics metabolism MeSH
- Cell Line, Tumor MeSH
- Tumor Suppressor Protein p53 genetics metabolism MeSH
- DNA Damage MeSH
- Proto-Oncogene Proteins c-mdm2 genetics metabolism MeSH
- RNA Recognition Motif Proteins genetics metabolism MeSH
- Base Sequence MeSH
- Protein Structure, Tertiary MeSH
- Protein Binding MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA Primers MeSH
- MDM2 protein, human MeSH Browser
- RNA, Messenger MeSH
- Tumor Suppressor Protein p53 MeSH
- Proto-Oncogene Proteins c-mdm2 MeSH
- RNA Recognition Motif Proteins MeSH
The p53 tumor suppressor and its key regulator MDM2 play essential roles in development, ageing, cancer, and cellular stress responses in mammals. Following DNA damage, MDM2 interacts with p53 mRNA in an ATM kinase-dependent fashion and stimulates p53 synthesis, whereas under normal conditions, MDM2 targets the p53 protein for degradation. The peptide- and RNA motifs that interact with MDM2 are encoded by the same conserved BOX-I sequence, but how these interactions have evolved is unknown. Here, we show that a temperature-sensitive structure in the invertebrate Ciona intestinalis (Ci) p53 mRNA controls its interaction with MDM2. We also show that a nonconserved flanking region of Ci-BOX-I domain prevents the p53-MDM2 protein-protein interaction. These results indicate that the temperature-regulated p53 mRNA-MDM2 interaction evolved to become kinase regulated in the mammalian DNA damage response. The data also suggest that the negative regulation of p53 by MDM2 via protein-protein interaction evolved in vertebrates following changes in the BOX-I flanking sequence.
Department of Medical Biosciences Umeå University Umeå Sweden
Edinburgh Cancer Research UK Centre the University of Edinburgh Edinburgh United Kingdom
Équipe Labellisée Ligue Contre le Cancer Université Paris 7 INSERM UMR 1162 Paris France
UPMC CNRS FR2424 Station Biologique de Roscoff Roscoff France
References provided by Crossref.org
Thermal stress, p53 structures and learning from elephants
The Elephant Evolved p53 Isoforms that Escape MDM2-Mediated Repression and Cancer
p53 mRNA Metabolism Links with the DNA Damage Response
Shaping the regulation of the p53 mRNA tumour suppressor: the co-evolution of genetic signatures
The p53 mRNA: an integral part of the cellular stress response
A single synonymous mutation determines the phosphorylation and stability of the nascent protein
