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. 2015 Mar 30;112(15):4624–4629. doi: 10.1073/pnas.1420833112

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Fig. 6. — Regulation of MDMX intramolecular interactions by CK1α. (A and B) MDMXc3 was cotransfected with CK1α and CK1α-K46D kinase-dead mutant into U2OS cells, and the changes in intramolecular interactions were analyzed by using PFR assay. (C) A model of MDMX intramolecular interactions. MDMX can assume multiple conformational states. I, a closed state of weak p53 binding and cytoplasmic localization due to intramolecular interactions. II, interaction with CK1α opens the N terminus for p53 binding. III, DNA damage recruits 14-3-3 and disrupts binding to CK1α, inhibits the N terminus, and exposes the RING to mediate nuclear import and heterodimerization with MDM2. ATM/Chk2 and WIP1-mediated phosphorylation and dephosphorylation alter the balance between the conformational states.