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

Warning

This publication doesn't include Faculty of Economics and Administration. It includes Faculty of Medicine. Official publication website can be found on muni.cz.
Authors

KOSZTYU Pavlína CETKOVSKÁ Kateřina VOUSDEN Karen H. ULDRIJAN Stjepan

Year of publication 2012
Type Article in Periodical
Magazine / Source FEBS Letters
MU Faculty or unit

Faculty of Medicine

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:

You are running an old browser version. We recommend updating your browser to its latest version.