PRT4165 is a potent inhibitor of PRC1-mediated H2A ubiquitylation.
PRT4165 is a potent inhibitor of PRC1-mediated H2A ubiquitylation. In vitro E3 ubiquitin ligase activity assays reveal that PRT4165 inhibits both RNF2 and RING 1A, but not RNF8 nor RNF168. In the presence of PRT4165, H2A ubiquitylation could be completely inhibited regardless of whether RING1 or RNF2 contributes the E3 ubiquitin ligase activity. Treatment of cells for 60 min with 50 μM PRT4165 results in a dramatic reduction in total ubiquitylated histone H2A. It is also found that longer exposure of the cells with the PRT4165 (30 and 60 min) leads to increased levels of γ-H2AX in unirradiated cells. PRT4165 inhibits double-strand break (DSB) repair at the 8-h time point compare with mock treated cells. Cells treated with increasing concentrations of PRT4165 show increasing numbers of cells in G2/M[1].
References:
[1]. Ismail IH, et al. A small molecule inhibitor of polycomb repressive complex 1 inhibits ubiquitin signaling at DNA double-strand breaks. J Biol Chem. 2013 Sep 13;288(37):26944-54.