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Electrophilic PROTACs that degrade nuclear proteins by engaging DCAF16

By Xiaoyu Zhang, Vincent M Crowley, Thomas G Wucherpfennig, Melissa M Dix, Benjamin F Cravatt

Posted 15 Oct 2018
bioRxiv DOI: 10.1101/443804 (published DOI: 10.1038/s41589-019-0279-5)

Ligand-dependent protein degradation has emerged as a compelling strategy to pharmacologically control the protein content of cells. So far, only a limited number of E3 ligases have been found to support this process. Here, we use a chemical proteomic strategy to discover that DCAF16 - a poorly characterized substrate recognition component of CUL4-DDB1 E3 ubiquitin ligases - promotes nuclear-restricted protein degradation upon modification by cysteine-directed heterobifunctional electrophilic compounds.

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