UCSD Molecule Pages
- Author(s): Irminger-Finger, Irmgard
- et al.
BARD1 was originally identified as a protein interacting with BRCA1, the breast cancer predisposition gene product. BARD1, like BRCA1, has an amino-terminal RING-finger domain and carboxy-terminal BRCT domains. In addition, BARD1 has three ankyrin repeats adjacent to the BRCT domains. BARD1 and BRCA1 form a stable heterodimer via their RING-finger domains. BRCA1, like many RING-finger proteins, has E3 ubiquitin ligase activity, which is amplified when in association with BARD1. By contrast, BARD1 alone has no such activity. The binding of BARD1 to BRCA1 stabilizes BRCA1 and, to some extent, BARD1. BARD1 and BRCA1 are co-expressed in most proliferating tissues and are localized to the nucleus. Based mostly on its ubiquitin ligase activity, the BARD1/BRCA1 complex has functions in DNA repair, transcriptional regulation, chromatin condensation, cell-cycle regulation, mitotic spindle formation and cytokinesis. BARD1 is highly conserved, having orthologs in many species. In mice, BARD1 has essential functions during development, and Bard1-null mice, like Brca1-null mice, die between embryonic days 7 and 8, suggesting that the defect is caused by the lack of a functional BARD1/BRCA1 heterodimer. Whereas only a few somatic and germline mutations of BARD1 have been found associated with breast, ovarian and endometrial cancer, nine commonly found alleles of BARD1 that contain single nucleotide polymorphisms have been found to be significantly associated with childhood neuroblastoma. In breast and ovarian cancers, truncated forms of BARD1 derived by differential RNA splicing are highly upregulated and are localized to the cytoplasm. The expression of these BARD1 isoforms in breast and ovarian cancer is correlated with a poor prognosis.