Selective p300 degradation via peptide PROTAC: a new therapeutic strategy for advanced prostate cancers

p300 and its paralog CREB-binding protein (CBP) are essential coactivators for many cancer-associated transcription factors. In prostate cancer, the transcriptional activity of the androgen receptor (AR) relies on p300/CBP, which catalyzes AR acetylation to enhance coactivator binding, and deposits histone acetylation at target enhancers to program a cancer-specific AR-dependent transcriptome.1–3 Additionally, the expression of AR and various tumor-promoting factors, such as c-Myc and FOXA1, also depends on p300 and super enhancer activities.