Mutational analysis of Mdm2 C-terminal tail suggests an evolutionarily conserved role of its length in Mdm2 activity toward p53 and indicates structural differences between Mdm2 homodimers and Mdm2/MdmX heterodimers

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F12%3A00057309" target="_blank" >RIV/00216224:14110/12:00057309 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.4161/cc.11.5.19445" target="_blank" >http://dx.doi.org/10.4161/cc.11.5.19445</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.4161/cc.11.5.19445" target="_blank" >10.4161/cc.11.5.19445</a>

Result language

angličtina

Original language name

Mutational analysis of Mdm2 C-terminal tail suggests an evolutionarily conserved role of its length in Mdm2 activity toward p53 and indicates structural differences between Mdm2 homodimers and Mdm2/MdmX heterodimers

Original language description

Mdm2 can mediate p53 ubiquitylation and degradation either in the form of the Mdm2 homodimer or Mdm2/MdmX heterodimer. The ubiquitin ligase activity of these complexes resides mainly in their respective RING finger domains and also requires adjacent C-terminal tails. So far, structural studies have failed to show significant differences between Mdm2 RING homodimers and Mdm2/MdmX RING heterodimers. Here, we report that not only the primary amino acid sequence, but also the length of the C-terminal tail of Mdm2 is highly conserved through evolution and plays an important role in Mdm2 activity toward p53. Mdm2 mutants with extended C termini do not ubiquitylate p53 despite being capable of forming Mdm2 homodimers through both RING-acidic domain and RING-RING interactions. All extended mutants also retained the ability to interact with MdmX, and this interaction led to reactivation of their E3 ubiquitin ligase activity.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

<a href="/en/project/GA301%2F09%2F1324" target="_blank" >GA301/09/1324: Function of the central domain of oncoprotein Mdm2 and its novel binding partners in the regulation of p53 tumour suppressor protein</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2012

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cell Cycle

ISSN

1538-4101

e-ISSN

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Volume of the periodical

11

Issue of the periodical within the volume

5

Country of publishing house

US - UNITED STATES

Number of pages

10

Pages from-to

953-962

UT code for WoS article

000300989700024

EID of the result in the Scopus database

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