COMM domain-containing protein 4 (COMMD4)

COMM domain-containing protein 4 (COMMD4) is a member of the copper metabolism MURR1 domain (COMMD) family that acts as a chromatin-associated protein involved in the regulation of genomic stability, particularly at sites of DNA double-strand breaks (DSBs)[1][3]. COMMD4 binds histones H2A and H2B and regulates their ubiquitination by the RNF20/40 E3 ubiquitin ligase complex, thereby controlling chromatin remodeling and the accessibility of DNA repair machinery at damage sites. COMMD4 plays a critical role in both homologous recombination and non-homologous end joining repair pathways. Its depletion results in defective DNA repair, increased cell death, and increased sensitivity to DNA-damaging agents. COMMD4 is upregulated in various cancers including non-small cell lung cancer and gliomas, where its expression is associated with poor prognosis and therapeutic resistance. Targeting COMMD4 or its interactions has been proposed as a potential cancer therapeutic strategy, although no specific drugs are clinically approved for this purpose as of 2024[1][2][3][4][5][7].

Other names

FLJ20452COMM domain containing 4COMMD4copper metabolism gene MURR1 domain-containing protein 4

Sensitization to DNA-damaging agents by disrupting DNA repair (through COMMD4 inhibition or depletion)[4][3]