Polycomb repressive complex 1 (PRC1)

Polycomb repressive complex 1 (PRC1) is a fundamental epigenetic regulatory assembly that plays a critical role in gene silencing and the maintenance of cellular identity [2, 5]. It functions primarily as an E3 ubiquitin ligase, catalyzing the monoubiquitination of histone H2A at lysine 119 (H2AK119ub1), a modification that promotes chromatin compaction and prevents transcriptional activation [4, 11]. The complex is heterogeneous, typically comprising a catalytic core of RING1A or RING1B paired with one of several Polycomb group ring finger (PCGF) proteins, most notably BMI1 (PCGF4) [4, 12]. PRC1 is frequently dysregulated in various cancers, including acute myeloid leukemia and several solid tumors, where it supports the survival and self-renewal of cancer stem cells by repressing tumor suppressor genes [3, 9]. Consequently, PRC1 has emerged as a significant therapeutic target, with small-molecule inhibitors like RB-3 and RB-231 being developed to disrupt its E3 ligase activity or its association with chromatin [7, 16]. These inhibitors aim to induce the differentiation of malignant cells and restore the expression of silenced genes [8, 12]. However, therapeutic intervention must be carefully managed due to the essential role of PRC1 in normal development and the maintenance of healthy stem cell populations [13, 14].

Other names

PRC1Polycomb group complex 1PcG complex 1

Inhibition of E3 ubiquitin ligase activity (specifically the RING1B-BMI1 core) and disruption of PRC1-nucleosome binding to reduce H2AK119ub1 levels, leading to the de-repression of target genes and induction of cellular differentiation [4, 7, 12].