Enhancer of Zeste Homolog Inhibitory Protein (EZHIP)

Enhancer of Zeste Homolog Inhibitory Protein (EZHIP), also known as CXorf67, is a critical endogenous regulator of the Polycomb Repressive Complex 2 (PRC2) (UniProt Q96LR5). It functions by mimicking the lysine 27-to-methionine (H3K27M) mutation found in histone H3, which leads to the global loss of H3K27 trimethylation (H3K27me3), a repressive epigenetic mark (Nature Communications, 2019; Cancer Cell, 2019). This inhibition of EZH2-mediated methyltransferase activity results in the derepression of genes involved in cell proliferation and development (Nature Medicine, 2019). EZHIP is highly expressed in specific pediatric brain tumors, such as posterior fossa ependymoma group A (PFA), where it acts as a primary oncogenic driver (Nature Communications, 2019). Because of its specific expression in tumors and its role in epigenetic reprogramming, EZHIP is a significant target for therapeutic intervention, with research focusing on disrupting its interaction with PRC2 or inducing its degradation (Journal of Clinical Oncology, 2020).

Other names

CXorf67Chromosome X open reading frame 67EZH inhibitory proteinProtein EZHIP

EZHIP acts as a competitive inhibitor of the EZH2 methyltransferase subunit of the PRC2 complex by mimicking the H3K27M oncohistone mutation (Nature Communications, 2019; Cancer Cell, 2019).