Regulation of BRCC, a Holoenzyme Complex Containing BRCA1 and BRCA2, by a Signalosome-like Subunit and Its Role in DNA Repair

Dong, Yongchun; Hakimi, Mohamed‐Ali; Chen, Xiaowei; Kumaraswamy, Easwari; Cooch, Neil; Godwin, Andrew K.; Shiekhattar, Ramin

doi:10.1016/s1097-2765(03)00424-6

Cited by 256 publications

(288 citation statements)

References 55 publications

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“…37 BRCC enhances cellular survival after DNA damage by ubiquitin E3 ligase activity. Interestingly, association of BRE to this complex further enhances the E3 ligase activity.…”

Section: Discussionmentioning

confidence: 99%

High BRE expression in pediatric MLL-rearranged AML is associated with favorable outcome

et al. 2010

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Translocations involving the mixed lineage leukemia (MLL) gene, localized at 11q23, frequently occur in pediatric acute myeloid leukemia (AML). We recently reported differences in prognosis between the different translocation partners, suggesting differences in biological background. To unravel the latter, we used microarrays to generate gene expression profiles of 245 pediatric AML cases, including 53 MLLrearranged cases. Thereby, we identified a specific gene expression signature for t(9;11)(p22;q23), and identified BRE (brain and reproductive organ expressed) to be discriminative for t(9;11)(p22;q23) (Po0.001) when compared with other MLL subtypes. Patients with high BRE expression showed a significantly better 3-year relapse-free survival (pRFS) (80 ± 13 vs 30 ± 10%, P ¼ 0.02) within MLL-rearranged AML cases. Moreover, multivariate analysis identified high BRE expression as an independent favorable prognostic factor within pediatric AML for RFS (HR ¼ 0.2, P ¼ 0.04). No significant differences were identified for 3-year event-free survival or for 3-year overall survival. Forced expression of BRE did not result in altered cell proliferation, apoptosis or drug sensitivity, which could explain the favorable outcome. In conclusion, overexpression of the BRE gene is predominantly found in MLL-rearranged AML with t(9;11)(p22;q23). Although further investigation for the role of BRE in leukemogenesis and outcome is warranted, high BRE expression is an independent prognostic factor for pRFS in pediatric AML.

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“…37 BRCC enhances cellular survival after DNA damage by ubiquitin E3 ligase activity. Interestingly, association of BRE to this complex further enhances the E3 ligase activity.…”

Section: Discussionmentioning

confidence: 99%

High BRE expression in pediatric MLL-rearranged AML is associated with favorable outcome

et al. 2010

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“…Certain point mutant disease-predisposing alleles of BRCA1 disrupt these interactions, indicating that these interactions are clinically relevant. BRCA1 forms complexes with a large number of other protein interaction partners, including the Mre11/Rad50/NBS1 (MRN) heterotrimer (a complex involved in the early recognition of DSBs), BRCA2/FANCD1, Rad51 and other Fanconi Anemia gene products, as well as with a number of chromatin-modifying factors [124][125][126]. A recent biochemical purification of BARD1 revealed at least three distinct BRCA1/BARD1 complexes: one containing BACH1, the DNA damage responsive protein, TopBP1 and the Mlh1 mismatch repair protein; one containing MRN and CtIP; one containing BRCA2 and Rad51.…”

Section: Molecular Functions Of Brca1 and Brca2mentioning

confidence: 99%

Minding the gap: The underground functions of BRCA1 and BRCA2 at stalled replication forks

Nagaraju

Scully

2007

DNA Repair

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The hereditary breast and ovarian cancer predisposition genes, BRCA1 and BRCA2, participate in the repair of DNA double strand breaks by homologous recombination. Circumstantial evidence implicates these genes in recombinational responses to DNA polymerase stalling during the S phase of the cell cycle. These responses play a key role in preventing genomic instability and cancer. Here, we review the current literature implicating the BRCA pathway in HR at stalled replication forks and explore the hypothesis that BRCA1 and BRCA2 participate in the recombinational resolution of single stranded DNA lesions termed "daughter strand gaps", generated during replication across a damaged DNA template.

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“…BRE, in combination with BRCC36, was shown to enhance the E3 ubiquitin ligase activity of BARD1 and BRCA1 complex in vitro. The protein was also shown to have a protective role against ionizing irradiation-induced cell death (Dong et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

BRE is an antiapoptotic protein in vivo and overexpressed in human hepatocellular carcinoma

Chan

Ching

et al. 2007

Oncogene

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BRE binds to the cytoplasmic domains of tumor necrosis factor receptor-1 and Fas, and in cell lines can attenuate death receptor-initiated apoptosis by inhibiting t-BIDinduced activation of the mitochondrial apoptotic pathway. Overexpression of BRE by transfection can also attenuate intrinsic apoptosis and promote growth of the transfected Lewis lung carcinoma line in mice. There is, however, a complete lack of in vivo data about the protein.Here, we report that by using our BRE-specific monoclonal antibody on the immunohistochemistry of 123 specimens of human hepatocellular carcinoma (HCC), significant differences in BRE expression levels between the paired tumoral and non-tumoral regions (Po2.2eÀ16) were found. Marked overexpression of BRE was detected in majority of the tumors, whereas most non-tumoral regions expressed the same low level of the protein as in normal livers. To investigate whether BRE overexpression could promote cell survival in vivo, liver-specific transgenic BRE mice were generated and found to be significantly resistant to Fas-mediated lethal hepatic apoptosis. The transgenic model also revealed post-transcriptional regulation of Bre level in the liver, which was not observed in HCC and non-HCC cell lines. Indeed, all cell lines analysed express high levels of BRE. In conclusion, BRE is antiapoptotic in vivo, and may promote tumorigenesis when overexpressed.

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Regulation of BRCC, a Holoenzyme Complex Containing BRCA1 and BRCA2, by a Signalosome-like Subunit and Its Role in DNA Repair

Cited by 256 publications

References 55 publications

High BRE expression in pediatric MLL-rearranged AML is associated with favorable outcome

High BRE expression in pediatric MLL-rearranged AML is associated with favorable outcome

Minding the gap: The underground functions of BRCA1 and BRCA2 at stalled replication forks

BRE is an antiapoptotic protein in vivo and overexpressed in human hepatocellular carcinoma

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