Dysfunctional BRCA1 is only indirectly linked to multiple centrosomes

Hut, Henderika M.J.; Rembacz, Krzysztof P.; Lemstra, Willy; Cappellen, Wiggert A. van; Kampinga, Harm H.; Sibon, Ody C. M.

doi:10.1038/sj.onc.1208859

Cited by 16 publications

(15 citation statements)

References 22 publications

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“…Likewise, the reported Cep63-dependent presence of Cdk1 at centrosomes [138] is almost certainly due to antibody cross-reactivity with Cep152 [139]. Thus, when interpreting immunocytochemical data reporting on unexpected centrosome-associations of particular proteins, it would seem wise to consider carefully the possibility of antibody-related artefacts [135,137,139,140]. Not only have proteins with well-established functions in DNA damage response pathways been reported to reside at centrosomes, but the opposite is also true: genuine centrosomal proteins have been implicated in DNA damage response.…”

Section: Centrosomes As Signalling Platforms In Vertebrates? (A) Cellmentioning

confidence: 99%

“…Moreover, APC/C activity was shown to oscillate, leading to successive rounds of Cdk2 and separase activation in the arrested cells [161]. Although centrosome amplification does not necessarily require passage through mitosis [159], we emphasize that supernumerary centrosomes are expected to arise whenever cells with damaged DNA fail to arrest at the G2/M checkpoint and then advance to abortive divisions [16,140]. The physiological significance of centrosomal responses to DNA damage remains to be fully understood, but the possibility has been raised that centrosome fragmentation or amplification may constitute a safeguard mechanism to kill cells with DNA damage via induction of division failures [156,159].…”

Section: Centrosomes As Signalling Platforms In Vertebrates? (A) Cellmentioning

confidence: 99%

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Centrosomes as signalling centres

Arquint

Gabryjonczyk

Nigg

2014

Phil. Trans. R. Soc. B

134

114

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Centrosomes—as well as the related spindle pole bodies (SPBs) of yeast—have been extensively studied from the perspective of their microtubule-organizing roles. Moreover, the biogenesis and duplication of these organelles have been the subject of much attention, and the importance of centrosomes and the centriole–ciliary apparatus for human disease is well recognized. Much less developed is our understanding of another facet of centrosomes and SPBs, namely their possible role as signalling centres. Yet, many signalling components, including kinases and phosphatases, have been associated with centrosomes and spindle poles, giving rise to the hypothesis that these organelles might serve as hubs for the integration and coordination of signalling pathways. In this review, we discuss a number of selected studies that bear on this notion. We cover different processes (cell cycle control, development, DNA damage response) and organisms (yeast, invertebrates and vertebrates), but have made no attempt to be comprehensive. This field is still young and although the concept of centrosomes and SPBs as signalling centres is attractive, it remains primarily a concept—in need of further scrutiny. We hope that this review will stimulate thought and experimentation.

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Section: Centrosomes As Signalling Platforms In Vertebrates? (A) Cellmentioning

confidence: 99%

Section: Centrosomes As Signalling Platforms In Vertebrates? (A) Cellmentioning

confidence: 99%

Centrosomes as signalling centres

Arquint

Gabryjonczyk

Nigg

2014

Phil. Trans. R. Soc. B

134

114

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“…Because BRCA1 localizes to centrosomes at all phases of the cell cycle (5), it is likely that the BRCA1 ubiquitin ligase activity is directly involved in regulating centrosome function. Although BRCA1 localization to the centrosome was questioned in one study in which the green fluorescent protein fusion of BRCA1 failed to localize to the centrosome (17), a number of other reports have shown endogenous BRCA1 localization to the centrosome (4,5,18,19).…”

Section: Introductionmentioning

confidence: 99%

Aurora-A Kinase Regulates Breast Cancer–Associated Gene 1 Inhibition of Centrosome-Dependent Microtubule Nucleation

et al. 2007

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Breast cancer-associated gene 1 (BRCA1) regulates the duplication and the function of centrosomes in breast cells. We have previously shown that BRCA1 ubiquitin ligase activity directly inhibits centrosome-dependent microtubule nucleation. However, there is a paradox because centrosome microtubule nucleation potential is highest during mitosis, a phase when BRCA1 is most abundant at the centrosome. In this study, we resolve this conundrum by testing whether centrosomes from cells in M phase are regulated differently by BRCA1 when compared with other phases of the cell cycle. We observed that BRCA1-dependent inhibition of centrosome microtubule nucleation was high in S phase but was significantly lower during M phase. The cell cycle-specific effects of BRCA1 on centrosome-dependent microtubule nucleation were detected in living cells and in cell-free experiments using centrosomes purified from cells at specific stages of the cell cycle. We show that Aurora-A kinase modulates the BRCA1 inhibition of centrosome function by decreasing the E3 ubiquitin ligase activity of BRCA1. In addition, dephosphorylation of BRCA1 by protein phosphatase 1A enhances the E3 ubiquitin ligase activity of BRCA1. These observations reveal that the inhibition of centrosome microtubule nucleation potential by the BRCA1 E3 ubiquitin ligase is controlled by Aurora-A kinase and protein phosphatase 1A-mediated phosphoregulation through the different phases of the cell cycle. [Cancer Res 2007;67(23):11186-94]

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“…However, centrosomal localization of BRCA1 was later challenged by one group: through the examination of exogenously introduced fluorescent protein-tagged BRCA1, they have concluded that BRCA1 does not localize to centrosomes. 30 The question of whether BRCA1 localizes to centrosomes had not been resolved. Here, we undertook a rigorous analysis of centrosome localization of BRCA1.…”

Section: Introductionmentioning

confidence: 99%