The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1

Otsuka, Kei; Yoshino, Yuki; Qi, Huicheng; Chiba, Natsuko

doi:10.3390/genes11080842

Cited by 12 publications

(12 citation statements)

References 96 publications

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“…In our cohort, p.Thr716Ala was only present in one patient. Moreover, several published studies have designated p.Thr716Ala as deleterious, arguing that it abolishes binding to OLA1, a protein interacting in BRCA1-BARD1 complex, leading to the alteration of BARD1 tumor suppressor activity 24 – 26 . Taking this in account, we consider that it should be regarded as VUS.…”

Section: Resultsmentioning

confidence: 99%

Apparent regional differences in the spectrum of BARD1 pathogenic variants in Spanish population and importance of copy number variants

Benito-Sánchez

Barroso

Fernández

et al. 2022

Sci Rep

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Only up to 25% of the cases in which there is a familial aggregation of breast and/or ovarian cancer are explained by germline mutations in the well-known BRCA1 and BRCA2 high-risk genes. Recently, the BRCA1-associated ring domain (BARD1), that partners BRCA1 in DNA repair, has been confirmed as a moderate-risk breast cancer susceptibility gene. Taking advantage of next-generation sequencing techniques, and with the purpose of defining the whole spectrum of possible pathogenic variants (PVs) in this gene, here we have performed a comprehensive mutational analysis of BARD1 in a cohort of 1946 Spanish patients who fulfilled criteria to be tested for germline pathogenic mutations in BRCA1 and BRCA2. We identified 22 different rare germline variants, being 5 of them clearly pathogenic or likely pathogenic large deletions, which account for 0.26% of the patients tested. Our results show that the prevalence and spectrum of mutations in the BARD1 gene might vary between different regions of Spain and expose the relevance to test for copy number variations.

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Section: Resultsmentioning

confidence: 99%

Apparent regional differences in the spectrum of BARD1 pathogenic variants in Spanish population and importance of copy number variants

Benito-Sánchez

Barroso

Fernández

et al. 2022

Sci Rep

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“…The proper formation of the complex composed of BRCA1, BARD1, and OLA1 is critical for the regulation of centrosome number (Figure 4B). 67 BRCA1 I42V decreases the interaction with OLA1 17 . Conversely, OLA1 E168Q, a substitution found in a breast cancer cell line, abrogates the interaction with BRCA1 17 .…”

Section: Roles Of Brca1 In Centrosome Regulationmentioning

confidence: 94%

Dysregulation of the centrosome induced by BRCA1 deficiency contributes to tissue‐specific carcinogenesis

Yoshino

Fang

et al. 2021

Cancer Science

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Alterations in breast cancer gene 1 (BRCA1), a tumor suppressor gene, increase the risk of breast and ovarian cancers. BRCA1 forms a heterodimer with BRCA1‐associated RING domain protein 1 (BARD1) and functions in multiple cellular processes, including DNA repair and centrosome regulation. BRCA1 acts as a tumor suppressor by promoting homologous recombination (HR) repair, and alterations in BRCA1 cause HR deficiency, not only in breast and ovarian tissues but also in other tissues. The molecular mechanisms underlying BRCA1 alteration‐induced carcinogenesis remain unclear. Centrosomes are the major microtubule‐organizing centers and function in bipolar spindle formation. The regulation of centrosome number is critical for chromosome segregation in mitosis, which maintains genomic stability. BRCA1/BARD1 function in centrosome regulation together with Obg‐like ATPase (OLA1) and receptor for activating protein C kinase 1 (RACK1). Cancer‐derived variants of BRCA1, BARD1, OLA1, and RACK1 do not interact, and aberrant expression of these proteins results in abnormal centrosome duplication in mammary‐derived cells, and rarely in other cell types. RACK1 is involved in centriole duplication in the S phase by promoting polo‐like kinase 1 activation by Aurora A, which is critical for centrosome duplication. Centriole number is higher in cells derived from mammary tissues compared with in those derived from other tissues, suggesting that tissue‐specific centrosome characterization may shed light on the tissue specificity of BRCA1‐associated carcinogenesis. Here, we explored the role of the BRCA1‐containing complex in centrosome regulation and the effect of its deficiency on tissue‐specific carcinogenesis.

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“…The centrosome is the main microtubule organization center in animal cells and is essential for the formation of the bipolar mitotic spindle. BRCA1 and BARD1 are located in the centrosome during the cell cycle, and BRCA1/BARD1 dimers ubiquitinate centrosome proteins to regulate centrosome function and then participate in the process of tumorigenesis (36). BARD1 is considered to be a potential pathogenic gene in colorectal cancer (37,38), endometrial cancer (39) and pancreatic cancer (40).…”

Section: Verification Of the Expression Level In The Hpa Databasementioning

confidence: 99%

Establishment and verification of a prognostic model of liver cancer by RNA-binding proteins based on the TCGA database

Apizi¹,

Wang²,

Wusiman³

et al. 2022

Transl Cancer Res TCR

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Background: Globally, liver cancer is one of the most common malignant tumors and is the third leading cause of cancer deaths. RNA-binding protein (RBP) is a general term for a class of proteins that bind to RNA to regulate metabolic processes. The expression of RNA-binding proteins is related to the prognosis of liver cancer patients. Methods:The RBP gene expression data of liver cancer were extracted from the TCGA database. First, the differentially expressed RBPs (DE RBPs) were selected through enrichment analysis and volcano mapping.Then, the prognosis-related RBP genes were selected through single-factor Cox regression analysis. The key prognosis-related RBPs were further screened by multifactor Cox regression analysis, and a formula for the patient's risk coefficient was obtained. Finally, based on the patient's risk score, a nomogram was established and verified.Results: We extracted 374 cancer tissue samples and 50 normal tissue samples with the clinical information from each sample. Through enrichment analysis, we screened 208 upregulated RBPs and 122 downregulated RBPs. Prognosis-related high-risk genes were EEF1E1,

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The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1

Cited by 12 publications

References 96 publications

Apparent regional differences in the spectrum of BARD1 pathogenic variants in Spanish population and importance of copy number variants

Apparent regional differences in the spectrum of BARD1 pathogenic variants in Spanish population and importance of copy number variants

Dysregulation of the centrosome induced by BRCA1 deficiency contributes to tissue‐specific carcinogenesis

Establishment and verification of a prognostic model of liver cancer by RNA-binding proteins based on the TCGA database

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