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New insight into the role of MDMX in MDM2-mediated p53 degradation and anti-cancer drug development
Author(s) -
Jing Yang,
Yanping Zhang
Publication year - 2021
Publication title -
oncoscience
Language(s) - English
Resource type - Journals
ISSN - 2331-4737
DOI - 10.18632/oncoscience.542
Subject(s) - mdmx , mdm2 , drug development , degradation (telecommunications) , cancer drugs , drug , cancer , cancer research , pharmacology , chemistry , medicine , computer science , biochemistry , gene , telecommunications
Inactivation of the tumor suppressor p53 has been generally accepted as a hallmark of tumor. MDM2 and MDMX, the two closely related proteins are considered to be critical for negatively regulating p53 activity through inhibitory binding to and post-translational modification of the p53 protein. We have demonstrated that MDMX facilitates MDM2-mediated p53 ubiquitination and degradation via recruitment of the ubiquitin-conjugating enzyme UbcH5c to the MDM2-MDMX heterooligomers. Here, we discuss our new findings from genetically engineered mouse models and a potential therapeutic strategy.

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