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. BARD 1 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 BARD 1 expression in apoptotic tumor cells was found associated with anti-BARD 1 immune response thus leading to new therapeutic approaches. (C) 2002 Elsevier Science Ltd. All rights reserved.