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The ubiquitin E3 ligase activity of BRCA1 and its biological functions

机译：BRCA1的泛素E3连接酶活性及其生物学功能

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The basal-like breast cancer, a new category of breast cancer associated with poor prognosis and possibly unique chemosensitivity, is a current topic in the breast cancer field. Evidence from multiple sources strongly indicate that impairment of BRCA1 pathways is responsible for this phenotype, implying the importance of BRCA1 not only in familial breast cancers but also in sporadic cancers. BRCA1 acts as a hub protein that coordinates a diverse range of cellular pathways to maintain genomic stability. BRCA1 participates in multiple cellular supercomplexes to execute its tasks and, in most of the complexes, BRCA1 exists as a RING heterodimer with BARD1 to provide ubiquitin E3 ligase activity that is required for its tumor suppressor function. It was revealed recently that the BRCA1 RING finger is capable of catalyzing multiple types of ubiquitination depending upon the interacting E2, the ubiquitin carrier protein. BRCA1 may catalyze distinct ubiquitination on different substrates as the situation demands. On the other hand, in response to DNA double-strand breaks where BRCA1 plays its major role for homologous recombination repair, recent evidence showed that ubiquitination is a critical step to recruit BRCA1 to the damaged site through UIM (ubiquitin interacting motif) containing protein RAP80. Thus, ubiquitin and BRCA1 likely affect each other in many ways to perform cellular functions. Elucidation of this mechanism in relation to cell survival is now much anticipated because it could be a key to predict chemosensitivity of basal-like breast cancer.
机译：基底样乳腺癌是与预后差和可能具有独特的化学敏感性相关的新型乳腺癌，是乳腺癌领域中的当前话题。来自多个来源的证据强烈表明，BRCA1通路的损伤是该表型的原因，这表明BRCA1不仅在家族性乳腺癌中而且在散发性癌症中都具有重要意义。 BRCA1充当枢纽蛋白，可协调多种细胞途径以维持基因组稳定性。 BRCA1参与多个细胞超复合体以执行其任务，并且在大多数复合体中，BRCA1与BARD1一起作为RING异二聚体存在，以提供其肿瘤抑制功能所需的泛素E3连接酶活性。最近发现，BRCA1 RING指能够根据相互作用的E2（泛素载体蛋白）催化多种类型的泛素化。根据情况需要，BRCA1可以在不同的底物上催化不同的泛素化。另一方面，针对DNA双链断裂，其中BRCA1在同源重组修复中起主要作用，最近的证据表明，泛素化是通过包含蛋白RAP80的UIM（泛素相互作用基序）将BRCA1募集到受损部位的关键步骤。 。因此，遍在蛋白和BRCA1可能以多种方式相互影响以执行细胞功能。现在人们非常期待阐明这种与细胞存活有关的机制，因为它可能是预测基底样乳腺癌化学敏感性的关键。

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