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

作者：Dolezelova Pavlina; Cetkovska Katerina; Vousden Karen H; Uldrijan Stjepan^*

来源：FEBS Letters, 2012, 586(16): 2225-2231.

DOI：10.1016/j.febslet.2012.05.034

• p53 degradation
• Mdm2
• Acidic domain
• Mutagenesis
• Ubiquitin ligase activity
• Binding partner

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.

• 出版日期2012-7-30