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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 a 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, roč.~11, č.~5, s.~953-962. ISSN~1538-4101. Dostupné z: https://dx.doi.org/10.4161/cc.11.5.19445.
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