Bivalent binding of p14arf to mdm2 ring and acidic domains inhibits e3 ligase function

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SUMMARY

    MDM2`s RING domain activity is regulated by dimerization, where MDM2 RING domain homodimerization or heterodimerization with the MDMX RING domain is essential for binding E2~Ub in the active conformation to confer E3 activity (Nomura et al, 2017; Magnussen et al, 2020). Binding of ribosomal proteins by the zinc_finger (ZnF) region inhibits MDM2`s activity toward p53 (Lohrum et al, 2003; Zhang et al, 2003; Dai et al, 2004; Dai and amp; Lu, 2004; Jin et al, 2004), and phosphorylation of MDM2 by Chk2, ATM, and CKI promotes MDM2 ubiquitination and degradation (Chen . . .

     

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