Chromobox homolog 4 (CBX4)

Chromobox homolog 4 (CBX4) is a nuclear protein that belongs to the polycomb group (PcG) family and functions as both a component of the PRC1 complex and as a SUMO E3 ligase[1][2][3][4][5]. Its chromodomain enables specific binding to di- and trimethylated lysines (H3K27me3, H3K9me3) on histone H3, facilitating gene silencing and maintenance of cell identity[2]. In addition, CBX4 contains SUMO-interacting motifs (SIMs) and a conserved Pc box. CBX4 is required for diverse processes including transcriptional silencing, DNA damage repair, cell cycle regulation, and cell proliferation[2][3]. It plays context-dependent roles in cancer, with evidence for both tumor suppressive and oncogenic activities: for example, it suppresses metastasis via HDAC3 recruitment in colorectal carcinoma, while promoting progression and stemness in hepatocellular carcinoma by enhancing HIF-1α sumoylation and VEGF expression[1][5][7]. CBX4 is also implicated in regulating cellular senescence and response to ionizing radiation through sumoylation-mediated DNA damage repair pathways[2][3]. No approved drugs currently target CBX4, though chemical probes (e.g., UNC3866) have been developed for research applications[6]. If further structure-specific or pathway-related information is needed, note that CBX4 functions through the PRC1 complex and its own SUMO E3 ligase activity, both critical for its biological roles[2][3][4][5][7].

Other names

Polycomb 2 homologPc2hPc2hPC2PC2NBP16Chromobox protein homolog 4NS5ATP1-binding protein 16Pc class 2 homolog (Drosophila)Chromobox-like protein 4

Modulation of gene expression through chromodomain-mediated binding to methylated histone H3 (H3K27me3/H3K9me3). SUMOylation of target proteins, e.g., BMI1, facilitating DNA damage repair. Recruitment of histone deacetylase 3 (HDAC3), leading to histone deacetylation and transcriptional repression (e.g., suppression of Runx2). Regulation of cellular senescence and stemness.