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Schematic illustrating in vitro reconstituted BRD4 neo-substrate ubiquitylation in the presence of neddylated CRL2VHL, UBE2R2 (light blue), and the PROTAC MZ1 (gray). Notice that the recombinant BRD4 protein contains multiple Lys residues (the actual number has been reduced for simplicity) that potentially may serve as sites of ubiquitin (UB; orange) priming of neo-substrate.

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