Mutational analysis reveals a dual role of Mdm2 acidic domain in the regulation of p53 stability
| Authors | |
|---|---|
| Year of publication | 2012 |
| Type | Article in Periodical |
| Magazine / Source | FEBS Letters |
| MU Faculty or unit | |
| Citation | |
| Doi | http://dx.doi.org/10.1016/j.febslet.2012.05.034 |
| Field | Oncology and hematology |
| Keywords | p53 degradation; Mdm2; Acidic domain; Mutagenesis; Ubiquitin ligase activity; Binding partner |
| Attached files | |
| Description | 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. |
| Related projects: |