p53 promotes its own polyubiquitination by enhancing the HDM2 and HDMX interaction
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F18%3A00077983" target="_blank" >RIV/00209805:_____/18:00077983 - isvavai.cz</a>
Result on the web
<a href="https://www.ncbi.nlm.nih.gov/pubmed/29524278" target="_blank" >https://www.ncbi.nlm.nih.gov/pubmed/29524278</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/pro.3405" target="_blank" >10.1002/pro.3405</a>
Alternative languages
Result language
angličtina
Original language name
p53 promotes its own polyubiquitination by enhancing the HDM2 and HDMX interaction
Original language description
HDM2 and HDMX are two homologs essential for controlling p53 tumor suppressor activity under normal conditions. Both proteins bind different sites on the p53 N-terminus, and while HDM2 has E3 ubiquitin ligase activity towards p53, HDMX does not. Nevertheless, HDMX is required for p53 polyubiquitination and degradation, but the underlying molecular mechanism remains unclear. Alone, HDMX and HDM2 interact via their respective C-terminal RING domains but here we show that the presence of p53 induces an N-terminal interface under normal cellular conditions. This results in an increase in HDM2-mediated p53 polyubiquitination and degradation. The HDM2 inhibitor Nutlin-3 binds the N-terminal p53 binding pocket and is sufficient to induce the HDM2-HDMX interaction, suggesting that the mechanism depends on allosteric changes that control the multiprotein complex formation. These results demonstrate an allosteric interchange between three different proteins (HDMX-HDM2-p53) and help to explain the molecular mechanisms of HDM2-inhibitory drugs.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
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
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Protein science
ISSN
0961-8368
e-ISSN
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Volume of the periodical
27
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
976-986
UT code for WoS article
000430824300008
EID of the result in the Scopus database
2-s2.0-85044265567