DDB1- and CUL4-associated factor 8-like protein 1 (DCAF8L1)

DCAF8L1 (DDB1- and CUL4-associated factor 8-like protein 1) is a member of the WD repeat protein family, functioning as a substrate receptor within the CRL4 E3 ubiquitin ligase complex. It directly binds to BRCA1 and BARD1, targeting them for ubiquitin-dependent proteasomal degradation and thereby negatively regulating their protein levels. DCAF8L1 plays a key role in DNA damage repair through its modulation of the BRCA1 pathway, impacting homologous recombination repair and cellular response to DNA-damaging agents. Overexpression of DCAF8L1 in breast cells results in reduced BRCA1/BARD1 abundance, increased genomic instability, and heightened sensitivity to genotoxic stress. This protein is encoded by an intronless, X-linked retrocopy gene, and does not have a clear ortholog in mice. Its function links the ubiquitin-proteasome system to cancer biology, particularly breast cancer, by contributing to tumorigenesis when dysregulated

Other names

DCAF8L1WDR42BWD repeat-containing protein 42BWD repeat domain 42BDDB1- and CUL4-associated factor 8-like protein 1

Drugs that target DCAF8L1, if discovered, would likely function by modulating ubiquitination/degradation of BRCA1/BARD1, impacting homologous recombination DNA repair and genomic stability