Mouse <i>Brca1</i>: localization, sequence analysis and identification of evolutionarily conserved domains

Abel, Kenneth; Xu, Junzhe; Yin, Gui Ying; Lyons, Robert H.; Meisler, Miriam H.; Weber, Barbara

doi:10.1093/hmg/4.12.2265

Cited by 66 publications

(47 citation statements)

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“…As illustrated in Figure 2a, Bard1 transcripts of approximately 6.0 and 3.0 kilobases are especially prevalent in RNA from spleen and testes (lanes 3 and 8, respectively), but not from heart, brain, lung, liver, skeletal muscle or kidney. The same expression pattern was obtained upon hybridization with pE18, a cDNA probe containing codons 8 ± 301 of mouse Brca1 (Bennett et al, 1995); in accord with previous reports (Abel et al, 1995;Bennett et al, 1995;Lane et al, 1995;Zabludo et al, 1996;Blackshear et al, 1998), this probe detects a major polyadenylated RNA species of 7.5 kilobases in the spleen and testes of adult mice (Figure 2b). The abundance of Bard1 and Brca1 transcripts in spleen and testes is especially striking given that these samples displayed the lowest levels of hybridization with the GAPDH control (Figure 2c; lanes 3 and 8).…”

supporting

confidence: 89%

“…As expected, sequence conservation is greater within the known protein motifs of BARD1, including the RING domain (86.7% identity), the three ankyrin repeats (90.1%) and the two BRCT domains (79.8%). Previous studies have shown that sequence conservation is also elevated within the RING (98.0% identity) and BRCT (63.7%) sequences of BRCA1 (Abel et al, 1995;Bennett et al, 1995;Lane et al, 1995;Sharan et al, 1995;Szabo et al, 1996).…”

mentioning

confidence: 94%

“…For example, the mouse and human counterparts of these proteins share less than 60% amino acid identity, a level of phylogenetic conservation that is remarkably low ± especially when compared with those of other known tumor suppressors (Abel et al, 1995;Bennett et al, 1995;Lane et al, 1995;Sharan et al, 1995;Szabo et al, 1996;Connor et al, 1997b;McAllister et al, 1997;. Moreover, yeast orthologs of the BRCA1 and BRCA2 genes are not found within the complete nucleotide sequence of the Figure 1 An alignment of the amino acid sequences of mouse and human BARD1.…”

mentioning

confidence: 99%

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Conservation of function and primary structure in the BRCA1-associated RING domain (BARD1) protein

et al. 1998

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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.

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supporting

confidence: 89%

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confidence: 94%

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confidence: 99%

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Conservation of function and primary structure in the BRCA1-associated RING domain (BARD1) protein

et al. 1998

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“…The speci®c antigen ± antibody interaction was blocked by the immunizing BRCA1 peptide (Figure 1a, lane 5). Despite di erences of the sequence in the epitope region between human and murine BRCA1 (Lane et al, 1995;Abel et al, 1995), the antiserum 579 identi®ed a polypeptide p215 BRCA1 in human and mouse cell lines (Figure 1b), indicating that the BRCA1 peptide likely exhibits some structural features shared between the intact rodent and human BRCA1 polypeptides. The polypeptide immunoprecipitated by 579 could be recognized by the commercially available polyclonal antibody M-20 (Santa Cruz, Inc.) that was generated against a Cterminal peptide of mouse BRCA1 (Figure 1c).…”

Section: Generation and Characterization Of Antibodies Against A Brcamentioning

confidence: 99%

Relationship of p215BRCA1 to tyrosine kinase signaling pathways and the cell cycle in normal and transformed cells

Zhang

Zhao

et al. 1997

Oncogene

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We have analysed the relationship of the products of two genes, neu and BRCA1, known to be important in human breast cancer. Highly speci®c antibodies that recognized both the rodent and human form of the BRCA1 gene product (M r 215 kDa, p215 BRCA1 ) were developed to facilitate these e orts. p215 BRCA1 was identi®ed as a tyrosine phosphorylated protein primarily localized in the nucleus of several breast cancer cell lines. In transformed murine and human cells, levels of p215 BRCA1 tyrosine phosphorylation were inversely correlated with the activity of the erbB family receptor-tyrosine-kinases and with the transformed growth features of these cells. Regulation of p215 BRCA1 tyrosine phosphorylation was also related to events in the cell cycle. Increased levels of p215 BRCA1 phosphotyrosine content were observed in NIH3T3 cells arrested at the G 2 /M transition. These ®ndings indicate that the products of BRCA1, neu, and erbB breast cancer genes participate in a common or shared signaling pathway important in cell growth and its regulation.

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“…The segregation of this amino acid change with the disease in the carrier's family could not be examined as the appropriate DNA samples were not available for analysis. The tyrosine at position 105 in BRCA1 protein lies outside the two regions conserved in human and mouse sequences (Abel et al, 1995). In murine Brca1 the position 105 is occupied by Phe, similar to Tyr.…”

Section: Introductionmentioning

confidence: 99%

Novel BRCA1 mutations and more frequent intron-20 alteration found among 236 women from Western Poland

et al. 1997

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Three di erent novel BRCA1 mutations, ®ve independent cases of the same 12 bp insertion-duplication in intron-20 and two novel rare BRCA1 sequence variants were identi®ed among 122 Polish women with positive, in most cases moderate family history of breast and/or ovarian cancer, 80 controls and 34 unselected breast cancer tissue specimens. All mutations and variants were germline. The 4153 delA frameshift mutation, the Tyr105Cys missense mutation and two cases of the alteration in intron-20 were found in the group of healthy women with positive family history. Two other cases of the intronic insertion were found in unselected controls. Their carriers had no family history of breast or ovarian cancer but other cancers occurred in their families. The 1782 Trp/STOP nonsense mutation and one case of the insertion in intron-20 were ®rst found in tissue specimens of breast cancer patient and breast/ovarian cancer patient, respectively. Their carriers also had no family history of breast or ovarian cancer. The distribution of the insertion in intron-20 in analysed groups and results of RT ± PCR experiments suggest a less prominent role for this variant considered earlier a splicing mutation. This study shows also, that more population-oriented research is needed, involving women with less profound or even no family history of breast and ovarian cancer, to better understand the role and signi®cance of di erent BRCA1 variants and mutations.Keywords: BRCA1; mutations and variants; SSCPheteroduplex analysis; Polish women; positive family history IntroductionApproximately one in ten women in western countries will develop breast cancer during their lifetime . In most cases the disease is sporadic; however, some 5 ± 10% of women with breast cancer inherit increased susceptibility to the disease (Claus et al., 1991). Within this fraction of breast cancer the germline mutations in BRCA1 (Miki et al., 1994) and BRCA2 genes most frequently form a favorable genetic background for the disease. Also at increased risk are the carriers of one abnormal allele of the ataxia telangiectasia gene (Swift et al., 1991), the carriers of rare minisatelite allele at the HRAS1 locus (Krontiris et al., 1993) and the members of Li Fraumeni families with germline mutation in the p53 gene (Srivastava et al., 1990).The BRCA1 gene located on chromosome 17q21 (Hall et al., 1990) is also linked to hereditary ovarian cancer (Narod et al., 1991). More than 400 BRCA1 sequence variants have been identi®ed thus far and deposited in Breast Cancer Information Core Database (Friend et al., 1995) which now contains about 150 di erent cancer predisposing mutations. Most of this knowledge comes from studies of breast and breastovarian cancer families. Therefore the known mutations are probably biased towards those with more severe e ects on phenotype. It is expected that less expressive mutations will be identi®ed when studies expand and include women with less profound family history and women from the general population. It is also very likely that the inciden...

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Mouse Brca1: localization, sequence analysis and identification of evolutionarily conserved domains

Cited by 66 publications

References 0 publications

Conservation of function and primary structure in the BRCA1-associated RING domain (BARD1) protein

Conservation of function and primary structure in the BRCA1-associated RING domain (BARD1) protein

Relationship of p215BRCA1 to tyrosine kinase signaling pathways and the cell cycle in normal and transformed cells

Novel BRCA1 mutations and more frequent intron-20 alteration found among 236 women from Western Poland

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