Reciprocally interacting domains of protein phosphatase 1 and focal adhesion kinase |
| |
Authors: | Mariarita Bianchi Stefania de Lucchini Michele Vietri Emma Villa-Moruzzi |
| |
Institution: | (1) Molecular Signalling Group, Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK;(2) Molecular Signalling Group, Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, U.K. |
| |
Abstract: | The Murine double-minute clone 2 (Mdm2) onco-protein is the principal regulator of the tumour suppressor, p53. Mdm2 acts as an E3-type ubiquitin ligase that mediates the ubiquitylation and turnover of p53 under normal, unstressed circumstances. In response to cellular stress, such as DNA damage, the Mdm2–p53 interaction is disrupted. Part of the mechanism of uncoupling p53 from Mdm2-mediated degradation involves hypo-phosphorylation of a cluster of phosphorylated serine residues in the central acidic domain of Mdm2. Here, we show that two of the residues within this domain that are phosphorylated in vivo, Ser-260 and Ser-269, are phosphorylated by CK2 in vitro. Treatment of cells with the CK2 inhibitor, 4,5,6,7-tetrabromo-2-azabenzimidazole (TBB), leads to the induction of p53 and downstream targets of p53 including Mdm2 itself and p21. These data are consistent with the idea that CK2-mediated phosphorylation of Mdm2 may regulate Mdm2-mediated p53 turnover. |
| |
Keywords: | CK2 DNA damage Mdm2 p53 phosphorylation |
本文献已被 PubMed SpringerLink 等数据库收录! |
|