Mutational analysis reveals a dual role of Mdm2 acidic domain in the regulation of p53 stability

• Autoři: KOSZTYU Pavlína; CETKOVSKÁ Kateřina; VOUSDEN Karen H.; ULDRIJAN Stjepan
• Rok publikování: 2012
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: FEBS Letters
• Fakulta / Pracoviště MU: Lékařská fakulta
• Doi: http://dx.doi.org/10.1016/j.febslet.2012.05.034
• Obor: Onkologie a hematologie
• Klíčová slova: p53 degradation; Mdm2; Acidic domain; Mutagenesis; Ubiquitin ligase activity; Binding partner

Přiložené soubory

• Dolezelova_et_al_2012_FEBS_Letters_-_PDF_Offprint.pdf

• Popis: 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.

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