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E3 Activity of MDM2 is not required for MDM2 to Inhibits Axin-induced p53 Activation
He Ying,Lian Guili,Ma Huanhuan #,Lin Shuyong,Li Qinxi *
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian 361102, China
*Correspondence author
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Funding: none
Opened online:18 May 2016
Accepted by: none
Citation: He Ying,Lian Guili,Ma Huanhuan.E3 Activity of MDM2 is not required for MDM2 to Inhibits Axin-induced p53 Activation[OL]. [18 May 2016] http://en.paper.edu.cn/en_releasepaper/content/4688749
 
 
MDM2 plays a crucial role in negatively regulating the functions of tumor suppressor p53. Here we show that MDM2 can inhibit Axin-stimulated p53-dependent apoptosis by suppressing p53 phosphorylation at Ser 46 and apoptosis-related p53 transactivational activity. Interestingly, the ubiquitin E3 ligase activity of MDM2 is not required for this inhibitory effect. Mechanically, either wildtype Mdm2 or its E3-dead mutant, disrupts the Axin-based HIPK2/p53 complex formation by blocking the binding of p53 and HIPK2 to Axin. Mdm2Δp53, a deletion mutant that lacks p53 binding domain fails to exert the inhibitory effect, demonstrating that the interaction of Mdm2 and p53, but not its E3 ligase activity toward p53 plays key role in suppressing Axin-stimulated p53 activation. Our results thus have revealed a novel aspect of the mechanism by which MDM2 regulates p53 activities.
Keywords:p53; MDM2; Axin; interaction
 
 
 

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