Disease relevance of Bard1

• BRCA1-associated RING domain (BARD1) was identified as a protein interacting with the breast cancer gene product BRCA1 [1].
• Upregulation of BARD1 alone is sufficient for stabilization of p53 and phosphorylation on serine-15, as shown in nonmalignant epithelial cells and ovarian cancer cells, NuTu-19, which are defective in apoptosis induction and express aberrant splice variants of BARD1 [2].

High impact information on Bard1

• BRCA1 is not required for but partially counteracts apoptosis induction by BARD1 [3].
• In vitro repression of Brca1-associated RING domain gene, Bard1, induces phenotypic changes in mammary epithelial cells [1].
• Partial repression of Bard1, achieved by the transfection of TAC-2 cells with plasmids constitutively expressing ribozymes or antisense RNAs, resulted in marked phenotypic changes, consisting of altered cell shape, increased cell size, high frequency of multinucleated cells, and aberrant cell cycle progression [1].
• Furthermore, Bard1-repressed cell clones overcame contact inhibition of cell proliferation when grown in monolayer cultures and lost the capacity to form luminal structures in three-dimensional collagen gels [1].
• To investigate the function of Bard1, we have reduced Bard1 gene expression in TAC-2 cells, a murine mammary epithelial cell line that retains morphogenetic properties characteristic of normal breast epithelium [1].

Biological context of Bard1

• To explore the genetic relationship between BRCA1 and BARD1, we have examined the phenotype of Bard1-null mice [4].
• Loss of Bard1, the heterodimeric partner of the Brca1 tumor suppressor, results in early embryonic lethality and chromosomal instability [4].
• 5. This result, together with the increased chromosomal aneuploidy of Bard1 mutant cells, indicates a role for Bard1 in maintaining genomic stability [4].
• We have constructed a series of BARD1 deletion mutants and analysed their cellular distribution and capacity to induce apoptosis [5].
• The tumor suppressor protein BARD1 plays a dual role in response to genotoxic stress: DNA repair as a BARD1-BRCA1 heterodimer and induction of apoptosis in a BRCA1-independent manner [5].

Anatomical context of Bard1

• Moreover, murine Bard1 retains the ability to associate in vivo with BRCA1, and its expression pattern in adult mice mirrors that of Brca1, with elevated levels of RNA transcripts found in the testes and spleen [6].
• These results demonstrate that Bard1 repression induces complex changes in mammary epithelial cell properties which are suggestive of a premalignant phenotype [1].

Associations of Bard1 with chemical compounds

• In assays for antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH), Granuflex, and two other hydrocolloid dressings (Comfeel Powder and Bard Absorption Dressing) showed significant ability to reduce DPPH to DPPH2 [7].

Other interactions of Bard1

• In the absence of p53, the developmental defects associated with Bard1 deficiency are partly ameliorated, and the lethality of Bard1; p53-nullizygous mice is delayed until E9 [4].
• In vivo BRCA1 forms a heterodimeric complex with the related BARD1 protein, and its enzymatic activity as a ubiquitin ligase is largely dependent upon its interaction with BARD1 [4].

Analytical, diagnostic and therapeutic context of Bard1

• As opposed to previous studies suggesting an exclusively nuclear localization of BARD1, we found, both in tissues and cell cultures, nuclear and cytoplasmic localization of BARD1 [5].

References