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BARD1, a tumor suppressor, with oncogenic functions in cancer

Defense Thèse de privat-docent : Univ. Genève, 2012
Abstract Mutations in the BRCA1 or BRCA2 genes predispose carriers to breast and ovarian cancer, but do not account for all cases of familial breast/ovarian cancer. BARD1 mutations are also associated with breast and ovarian cancer but are much less frequent. BARD1 and BRCA1 proteins form a stable complex, which acts as an E3 ubiquitin ligase. Ubiquitination and degradation of targets proteins essential for cell cycle control and response to DNA damage response presents part of the tumor suppressor functions of BRCA1 and BARD1. BARD1 can also be found independently of BRCA1 interacting with proteins involved in mRNA maturation, apoptosis, and mitosis, which might reflect tumor suppressor functions, but also essential functions for cell proliferation. Tumor cells express isoforms of BARD1 that cannot perform the tumor suppressor functions, and antagonize the wild type BARD1 and BRCA1. While first discovered in breast and ovarian cancer, BARD1 isoforms seem to play oncogenic roles in many epithelial cancers and could be targets for novel drug treatments and biomarkers of cancer.
Keywords BARD1BRCA1BRCA2CancerOncogenesPredisposition genesTumor suppressors
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IRMINGER, Irmgard. BARD1, a tumor suppressor, with oncogenic functions in cancer. Université de Genève. Thèse de privat-docent, 2012. https://archive-ouverte.unige.ch/unige:22051

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Deposited on : 2012-08-15

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