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@article{976730,
author = {Doleželová, Pavlína and Cetkovská, Kateřina and Vousden, Karen H. and Uldrijan, Stjepan},
article_number = {5},
doi = {http://dx.doi.org/10.4161/cc.11.5.19445},
keywords = {p53; Mdm2; RING domain; ubiquitylation; ubiquitin ligase; E3},
language = {eng},
issn = {1538-4101},
journal = {Cell Cycle},
title = {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},
volume = {11},
year = {2012}
}
TY - JOUR
ID - 976730
AU - Doleželová, Pavlína - Cetkovská, Kateřina - Vousden, Karen H. - Uldrijan, Stjepan
PY - 2012
TI - 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
JF - Cell Cycle
VL - 11
IS - 5
SP - 953-962
EP - 953-962
SN - 15384101
KW - p53
KW - Mdm2
KW - RING domain
KW - ubiquitylation
KW - ubiquitin ligase
KW - E3
N2 - 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. In contrast, only a subset of extended Mdm2 mutants was activated by the interaction with Mdm2 RING domain, suggesting that Mdm2 homodimers and Mdm2/MdmX heterodimers may not be structurally and functionally fully equivalent.
ER -
DOLEŽELOVÁ, Pavlína, Kateřina CETKOVSKÁ, Karen H. VOUSDEN and Stjepan ULDRIJAN. 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. \textit{Cell Cycle}. 2012, vol.~11, No~5, p.~953-962. ISSN~1538-4101. Available from: https://dx.doi.org/10.4161/cc.11.5.19445.
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