ArticleThe Journal of biological chemistry2012
Characterization of BRCA1 protein targeting, dynamics, and function at the centrosome: a role for the nuclear export signal, CRM1, and Aurora A kinase.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Sex-biased transcriptomic landscapes in bipolar disorder: integrating neurobiology and clinical heterogeneity through cross-study meta-analysis.Biology of sex differences · 2026Pooled it
- The Role of Aurora Kinase A in HBV-Associated Hepatocellular Carcinomas: A Molecular and Immunohistochemical Study.Diagnostics (Basel, Switzerland) · 2026Article
- The role of Aurora kinase A in hepatocellular carcinoma: Unveiling the intriguing functions of a key but still underexplored factor in liver cancer.Cell proliferation · 2024Review
- BAP1 loss induces mitotic defects in mesothelioma cells through BRCA1-dependent and independent mechanisms.Oncogene · 2023Article
- BRCA1 transports the DNA damage signal for CDDP-induced centrosome amplification through the centrosomal Aurora A.Cancer science · 2022Article
- Dysregulation of the centrosome induced by BRCA1 deficiency contributes to tissue-specific carcinogenesis.Cancer science · 2021Review
- Aurora kinase A, a synthetic lethal target for precision cancer medicine.Experimental & molecular medicine · 2021Review
- Review
- Fanconi Anemia Pathway: Mechanisms of Breast Cancer Predisposition Development and Potential Therapeutic Targets.Frontiers in cell and developmental biology · 2020Review
- Noncoding RNA Ginir functions as an oncogene by associating with centrosomal proteins.PLoS biology · 2018Article
- Identifying genes as potential prognostic indicators in patients with serous ovarian cancer resistant to carboplatin using integrated bioinformatics analysis.Oncology reports · 2018Article
- CRM1, a novel independent prognostic factor overexpressed in invasive breast carcinoma of poor prognosis.Oncology letters · 2018Article
- Crm1 knockdown by specific small interfering RNA reduces cell proliferation and induces apoptosis in head and neck cancer cell lines.Turkish journal of biology = Turk biyoloji dergisi · 2018Article
- Pharmacological treatment with inhibitors of nuclear export enhances the antitumor activity of docetaxel in human prostate cancer.Oncotarget · 2017Article
- Aurora A kinase regulates non-homologous end-joining and poly(ADP-ribose) polymerase function in ovarian carcinoma cells.Oncotarget · 2017Article
- Phenethyl isothiocyanate suppresses the metastasis of ovarian cancer associated with the inhibition of CRM1-mediated nuclear export and mTOR-STAT3 pathway.Cancer biology & therapy · 2017Article
- CRM1 Inhibitors for Antiviral Therapy.Frontiers in microbiology · 2017Review
- Chromosome region maintenance 1 expression and its association with clinical pathological features in primary carcinoma of the liver.Experimental and therapeutic medicine · 2016Article
- Characterization of Adenomatous Polyposis Coli Protein Dynamics and Localization at the Centrosome.Cancers · 2016Article
- The GTPase RAN regulates multiple steps of the centrosome life cycle.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2016Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BRCA1 is a DNA damage response protein and functions in the nucleus to stimulate DNA repair and at the centrosome to inhibit centrosome overduplication in response to DNA damage. The loss or mutation of BRCA1 causes centrosome amplification and abnormal mitotic spindle assembly in breast cancer cells. The BRCA1-BARD1 heterodimer binds and ubiquitinates γ-tubulin to inhibit centrosome amplification and promote microtubule nucleation; however regulation of BRCA1 targeting and function at the centrosome is poorly understood. Here we show that both N and C termini of BRCA1 are required for its centrosomal localization and that BRCA1 moves to the centrosome independently of BARD1 and γ-tubulin. Mutations in the C-terminal phosphoprotein-binding BRCT domain of BRCA1 prevented localization to centrosomes. Photobleaching experiments identified dynamic (60%) and immobilized (40%) pools of ectopic BRCA1 at the centrosome, and these are regulated by the nuclear export receptor CRM1 (chromosome region maintenance 1) and BARD1. CRM1 mediates nuclear export of BRCA1, and mutation of the export sequence blocked BRCA1 regulation of centrosome amplification in irradiated cells. CRM1 binds to undimerized BRCA1 and is displaced by BARD1. Photobleaching assays implicate CRM1 in driving undimerized BRCA1 to the centrosome and revealed that when BRCA1 subsequently binds to BARD1, it is less well retained at centrosomes, suggesting a mechanism to accelerate BRCA1 release after formation of the active heterodimer. Moreover, Aurora A binding and phosphorylation of BRCA1 enhanced its centrosomal retention and regulation of centrosome amplification. Thus, CRM1, BARD1 and Aurora A promote the targeting and function of BRCA1 at centrosomes.
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