BRCA1-dependent and independent functions of BARD1.

Breast cancer susceptibility gene 1 (BRCA1)-associated RING domain (BARD1) was discovered as a protein interacting with the RING domain of BRCA1. It is structurally homologous to BRCA1 with which it shares the conserved RING finger and BRCT domains. BARD1 is strongly expressed in spleen and testis, correlated with the expression of BRCA1. Co-localization of BARD1 with BRCA1 and other repair proteins indicate a function in DNA repair. A potential role of BARD1-BRCA1 complexes in ubiquitination of RNA Pol II, and the interaction of BARD1 with polyadenylation factor CstF-50, thus inhibiting mRNA processing, provide mechanisms for tumor suppression. BRCA1-independent functions of BARD1 were first noted by its inordinate expression in hormonally regulated uterine tissue. BARD1 repression lead to a premalignant phenotype in mammary gland epithelial cells. The interaction of BARD1 with NF-kappaB, suggests modulation of transcriptional activity independent of BRCA1. Elevated BARD1 expression in apoptotic tumor cells was found associated with anti-BARD1 immune response thus leading to new therapeutic approaches.