Critical Role for a Central Part of Mdm2 in the Ubiquitylation of p53
Open Access
- 1 July 2003
- journal article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 23 (14) , 4929-4938
- https://doi.org/10.1128/mcb.23.14.4929-4938.2003
Abstract
The stability of the p53 protein is regulated by Mdm2. By acting as an E3 ubiquitin ligase, Mdm2 directs the ubiquitylation of p53 and its subsequent degradation by the 26S proteasome. In contrast, the Mdmx protein, although structurally similar to Mdm2, cannot ubiquitylate or degrade p53 in vivo. To ascertain which domains determine this functional difference between Mdm2 and Mdmx and consequently are essential for p53 ubiquitylation and degradation, we generated Mdm2-Mdmx chimeric constructs. Here we show that, in addition to a fully functional Mdm2 RING finger, an internal domain of Mdm2 (residues 202 to 302) is essential for p53 ubiquitylation. Strikingly, the function of this domain can be fulfilled in trans, indicating that the RING domain and this internal region perform distinct activities in the ubiquitylation of p53.Keywords
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