Monday, April 13, 2015 10:44:54 PM
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Moffitt Cancer Center Researchers Develop New Method to Characterize the Structure of a Protein That Promotes Tumor Growth
Using a new assay, researchers find the structure of MDMX that controls its own interaction with tumor suppressor protein p53
http://www.newswise.com/articles/moffitt-cancer-center-researchers-develop-new-method-to-characterize-the-structure-of-a-protein-that-promotes-tumor-growth
Autoinhibition of MDMX by intramolecular p53 mimicry
http://m.pnas.org/content/early/2015/03/25/1420833112.abstract
MDMX protein is a critical regulator of p53 and a novel drug target. ****The current generation of MDM2 inhibitors does not inhibit MDMX. Therefore, their therapeutic efficacy will be influenced by poorly characterized MDMX functional status in tumors.**** Efforts to develop MDMX inhibitors have been largely unsuccessful, indicating gaps in our understanding of the structure and regulation of MDMX. This study provides evidence that MDMX-p53 binding is regulated by an autoinhibitory mechanism that involves intramolecular interaction in MDMX through p53 mimicry. The results suggest a mechanism by which DNA damage signaling inhibits MDMX and activates p53.
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