Chromobox protein homolog 3 (CBX3) (CBX3)

Chromobox protein homolog 3 (CBX3), also known as HP1 gamma (HP1γ), is a highly conserved epigenetic reader protein belonging to the heterochromatin protein 1 (HP1) family (UniProt). It features an N-terminal chromodomain that specifically recognizes and binds to di- and tri-methylated lysine 9 on histone H3 (H3K9me2/3), which is a key mark for transcriptionally silent heterochromatin (PubMed, NIH). Beyond its role in gene silencing and heterochromatin maintenance, CBX3 is involved in diverse cellular processes including DNA damage repair, RNA splicing, and transcriptional activation of specific genes (PubMed). In oncology, CBX3 is frequently overexpressed and acts as an oncoprotein in various malignancies, such as non-small cell lung cancer, gastric cancer, and colorectal cancer, where it promotes cell proliferation and survival by modulating pathways like PI3K/AKT and Wnt/β-catenin (NIH, PubMed). Therapeutic targeting of the CBX3 chromodomain aims to disrupt its interaction with methylated histones, thereby reversing aberrant gene repression or activation in cancer cells (PubMed). While small-molecule inhibitors like UNC7560 have been developed as chemical probes to study its function, achieving high selectivity over other HP1 isoforms remains a significant challenge in drug development (PubMed).

Other names

HP1 gammaHP1γHeterochromatin protein 1 homolog gammaHECHModifier 2 protein

Antagonism of the chromodomain-methyllysine interaction, specifically preventing the recognition of H3K9me2/3 marks on histone tails to disrupt epigenetic repression or aberrant gene activation (PubMed).