Lukas Lercher, Nina Simon, Andreas Bergmann, Marcel Tauchert, David Bochmann, Tarig Bashir, Torsten Neuefeind, Daniel Riley, Ben Danna, Paul Krawczuk, Vineet Pande, Aaron Patrick, Ruth Steele, Weixue Wang, Brent Rupnow, Peter Tummino, Sujata Sharma, Michael Finley
The dysregulation of the PRC1/2 complex plays a key role in lineage plasticity in prostate cancer and may be required to maintain neuroendocrine phenotype. [1] CBX2, a key component of the canonical PRC1 complex, is an epigenetic reader, recognizing trimethylated lysine on histone 3 (H3K27me3) [2] and is overexpressed in metastatic neuroendocrine prostate cancer. [3,4] We implemented a screening strategy using nucleosome substrates to identify inhibitors of CBX2 binding to chromatin. Construct design and phosphorylation state of CBX2 were critical for successful implementation and execution of an HTS library screen...
July 2022: SLAS Discovery