Targeted degradation of the enhancer lysine acetyltransferases CBP and p300
نویسندگان
چکیده
Summary The enhancer factors CREB-binding protein (CBP) and p300 (also known as KAT3A KAT3B) maintain gene expression programs through lysine acetylation of chromatin transcriptional regulators by scaffolding functions mediated several protein-protein interaction domains. Small molecule inhibitors that target some these domains have been developed; however, they cannot completely ablate p300/CBP function in cells. Here we describe a chemical degrader p300/CBP, dCBP-1. Leveraging structures ligand-bound domains, use in silico modeling ternary complex formation with the E3 ubiquitin ligase cereblon to enable design. dCBP-1 is exceptionally potent at killing multiple myeloma cells can abolish drives MYC oncogene expression. As an efficient this unique class acetyltransferases, useful tool alongside domain for dissecting mechanism which coordinate activity normal diseased
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ژورنال
عنوان ژورنال: Cell chemical biology
سال: 2021
ISSN: ['2451-9456', '2451-9448']
DOI: https://doi.org/10.1016/j.chembiol.2020.12.004