Conservation of function and primary structure in the BRCA1-associated RING domain (BARD1) protein.
The BRCA1 gene encodes a tumor suppressor that has been implicated in hereditary forms of breast and ovarian cancer. During S phase of the cell cycle, BRCA1 polypeptides are found in discrete nuclear bodies ('BRCA1 nuclear dots') together with HsRad51, a human homolog of the E. coli recA protein, and BARD1, a protein that interacts with BRCA1 to form a stable heterodimer. BARD1 is structurally similar to BRCA1 in that both molecules harbor an amino-terminal RING domain and two carboxy-terminal BRCT domains. Here we describe the amino acid sequence and expression pattern of murine Bard1. A comparison of the mouse and human sequences reveals that the recognizable protein motifs of BARD1 are well conserved, including the RING domain, the three tandem ankyrin repeats, and, to a lesser extent, the two BRCT domains. However, the remaining sequences of BARD1 display a markedly lower degree of phylogenetic conservation, comparable to those reported for BRCA1 and BRCA2. 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. These data suggest that BRCA1 and BARD1 have co-evolved to participate in a common pathway of tumor suppression.
Ayi
T C
TC
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Tsan
J T
JT
Hwang
L Y
LY
Bowcock
A M
AM
Baer
R
R
D000595:Amino Acid Sequence; D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism*; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002461:Cell Line, Transformed; D017124:Conserved Sequence; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases
D019313:BRCA1 Protein; D002352:Carrier Proteins; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; C491163:Bard1 protein, mouse; D044767:Ubiquitin-Protein Ligases