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  • The exact role of the central acidic domain of Mdm2 in p53 degradation remains unclear. We therefore performed a systematic and comprehensive analysis of the acidic domain using a series of short deletions and found that only a minor part of the domain was indispensable for Mdm2-mediated p53 ubiquitylation. Moreover, we identified a short stretch of acidic amino acids required for p53 degradation but not ubiquitylation, indicating that, in addition to p53 ubiquitylation, the acidic domain might be involved in a critical post-ubiquitylation step in p53 degradation. Rather than representing a single functional domain, different parts of the acidic region perform separate functions in p53 degradation, suggesting that it might be possible to therapeutically target them independently.
  • The exact role of the central acidic domain of Mdm2 in p53 degradation remains unclear. We therefore performed a systematic and comprehensive analysis of the acidic domain using a series of short deletions and found that only a minor part of the domain was indispensable for Mdm2-mediated p53 ubiquitylation. Moreover, we identified a short stretch of acidic amino acids required for p53 degradation but not ubiquitylation, indicating that, in addition to p53 ubiquitylation, the acidic domain might be involved in a critical post-ubiquitylation step in p53 degradation. Rather than representing a single functional domain, different parts of the acidic region perform separate functions in p53 degradation, suggesting that it might be possible to therapeutically target them independently. (en)
Title
  • Mutational analysis reveals a dual role of Mdm2 acidic domain in the regulation of p53 stability
  • Mutational analysis reveals a dual role of Mdm2 acidic domain in the regulation of p53 stability (en)
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  • Mutational analysis reveals a dual role of Mdm2 acidic domain in the regulation of p53 stability
  • Mutational analysis reveals a dual role of Mdm2 acidic domain in the regulation of p53 stability (en)
skos:notation
  • RIV/00216224:14110/12:00065570!RIV14-MZ0-14110___
http://linked.open...avai/predkladatel
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(ED1.100/02/0123), P(GA301/09/1324), P(NS10236)
http://linked.open...iv/cisloPeriodika
  • 16
http://linked.open...vai/riv/dodaniDat
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  • 152546
http://linked.open...ai/riv/idVysledku
  • RIV/00216224:14110/12:00065570
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • p53 degradation; Mdm2; Acidic domain; Mutagenesis; Ubiquitin ligase activity; Binding partner (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV
  • [4A481F7D9AA4]
http://linked.open...i/riv/nazevZdroje
  • FEBS Letters
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http://linked.open...v/svazekPeriodika
  • 586
http://linked.open...iv/tvurceVysledku
  • Uldrijan, Stjepan
  • Cetkovská, Kateřina
  • Kosztyu, Pavlína
  • Vousden, Karen H.
http://linked.open...ain/vavai/riv/wos
  • 000306694800004
issn
  • 0014-5793
number of pages
http://bibframe.org/vocab/doi
  • 10.1016/j.febslet.2012.05.034
http://localhost/t...ganizacniJednotka
  • 14110
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