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Quantitative Proteomics Analysis to Determine Specificity of PRC2 Degrader

ABSTRACT: To assess the effects of UNC6852 treatment on cellular protein levels more broadly, we performed global proteomics experiments using tandem mass tag (TMT) quantification comparing HeLa cells treated with UN6852 (10 μM, 24 hrs) to DMSO treated control cells. Whole proteome analysis resulted in the identification of >60,000 peptides corresponding to 5,452 quantifiable proteins. Notably, these data revealed that EED and EZH2 were selectively degraded by UNC6852 within the proteome.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Laura Herring

LAB HEAD: Lindsey James

PROVIDER: PXD016021 | Pride | 2020-01-09

REPOSITORIES: Pride

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Degradation of Polycomb Repressive Complex 2 with an EED-Targeted Bivalent Chemical Degrader.

Potjewyd Frances F Turner Anne-Marie W AW Beri Joshua J Rectenwald Justin M JM Norris-Drouin Jacqueline L JL Cholensky Stephanie H SH Margolis David M DM Pearce Kenneth H KH Herring Laura E LE James Lindsey I LI

Cell chemical biology 20191209 1

Protein degradation via the use of bivalent chemical degraders provides an alternative strategy to block protein function and assess the biological roles of putative drug targets. This approach capitalizes on the advantages of small-molecule inhibitors while moving beyond the restrictions of traditional pharmacology. Here, we report a chemical degrader (UNC6852) that targets polycomb repressive complex 2 (PRC2). UNC6852 contains an EED226-derived ligand and a ligand for VHL which bind to the WD4 ...[more]

PMID: 31831267

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