Rearrangement of Mitochondrial Pyruvate Dehydrogenase Subunit Dihydrolipoamide Dehydrogenase Protein-Protein Interactions by the MDM2 Ligand Nutlin-3
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F16%3AN0000033" target="_blank" >RIV/00209805:_____/16:N0000033 - isvavai.cz</a>
Result on the web
<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026170/" target="_blank" >https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026170/</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/pmic.201500501" target="_blank" >10.1002/pmic.201500501</a>
Alternative languages
Result language
angličtina
Original language name
Rearrangement of Mitochondrial Pyruvate Dehydrogenase Subunit Dihydrolipoamide Dehydrogenase Protein-Protein Interactions by the MDM2 Ligand Nutlin-3
Original language description
MDMX and MDM2 are two nonredundant essential regulators of p53 tumor suppressor activity. MDM2 controls p53 expression levels, whereas MDMX is predominantly a negative regulator of p53 trans-activity. The feedback loops between MDM2 and p53 are well studied and involve both negative and positive regulation on transcriptional, translational and post-translational levels but little is known on the regulatory pathways between p53 and MDMX. Here we show that overexpression of p53 suppresses mdmx mRNA translation in vitro and in cell-based assays. The core domain of p53 binds the 5′ untranslated region (UTR) of the mdmx mRNA in a zinc-dependent manner that together with a trans-suppression domain located in p53 N-terminus controls MDMX synthesis. This interaction can be visualized in the nuclear and cytoplasmic compartment. Fusion of the mdmx 5′UTR to the ovalbumin open reading frame leads to suppression of ovalbumin synthesis. Interestingly, the transcription inactive p53 mutant R273H has a different RNA-binding profile compared with the wild-type p53 and differentiates the synthesis of MDMX isoforms. This study describes p53 as a trans-suppressor of the mdmx mRNA and adds a further level to the intricate feedback system that exist between p53 and its key regulatory factors and emphasizes the important role of mRNA translation control in regulativ protein expression in the p53 pathway.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EB - Genetics and molecular biology
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Proteomics
ISSN
1615-9853
e-ISSN
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Volume of the periodical
16
Issue of the periodical within the volume
17
Country of publishing house
US - UNITED STATES
Number of pages
18
Pages from-to
2327-2344
UT code for WoS article
000383611400004
EID of the result in the Scopus database
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