文章：

BARD1是否比BRCA1更多？

Is there more to BARD1 than BRCA1?

原文发布日期：2006-05-01

DOI: 10.1038/nrc1878

类型: Review Article

开放获取: 否

要点：

1. BRCA1-associated ring domain 1 (BARD1) is the main binding partner of BRCA1 and is essential for the tumour-suppressor functions of BRCA1.
2. The BARD1–BRCA1 heterodimer has ubiquitin ligase activity that targets proteins involved in cell-cycle regulation and DNA repair for degradation.
3. BARD1 has a BRCA1-independent function in mediating p53-dependent apoptosis. It binds to p53, facilitating its phosphorylation and stabilization.
4. BARD1 is expressed in most proliferative tissues, including that of the breast, ovary and uterus. It is transcriptionally upregulated in response to DNA damage, hypoxia and hormone signalling. Its translation is activated by cell-cycle-dependent phosphorylation.
5. BARD1 is mutated or truncated in breast, ovarian and uterine tumour samples.
6. Depletion of BARD1 leads to early embryonic lethality in mice, and genomic instability in vitro and in vivo; phenotypes that are also observed for BRCA1 or BRCA2 deficiencies.

要点翻译：

1. BRCA1相关环结构域蛋白1（BARD1）是BRCA1的主要结合伴侣，对BRCA1的肿瘤抑制功能至关重要。
2. BARD1-BRCA1异源二聚体具有泛素连接酶活性，可靶向参与细胞周期调控和DNA修复的蛋白并促使其降解。
3. BARD1在介导p53依赖性凋亡过程中具有独立于BRCA1的功能：它能与p53结合，促进其磷酸化和稳定化。
4. BARD1在大多数增殖性组织（包括乳腺、卵巢和子宫组织）中均有表达。其转录水平会响应DNA损伤、缺氧和激素信号传导而上调，翻译过程则通过细胞周期依赖性磷酸化被激活。
5. 在乳腺癌、卵巢癌和子宫肿瘤样本中均发现BARD1存在突变或截断变异。
6. 小鼠模型中BARD1缺失会导致早期胚胎致死，并在体外和体内引发基因组不稳定性——这些表型在BRCA1或BRCA2缺陷时同样被观察到。

英文摘要：

It has been over a decade since mutations in BRCA1 and BRCA2 were found to be associated with a small number of familial breast cancer cases. BRCA1 is a large protein that interacts with many other proteins that have diverse functions, so it has been a challenge to determine how defects in its function could lead to cancer. One particular protein, BARD1, seems to be an important regulator of the tumour-suppressor function of BRCA1, as well as acting as a tumour suppressor itself. BARD1 is indispensable for cell viability, so loss-of-function mutations are rare, but mutations and truncations that alter its function might be involved in the pathogenesis of breast cancer.

摘要翻译： 

自发现BRCA1和BRCA2基因突变与少数家族性乳腺癌病例相关以来，已过去十余年。BRCA1是一种大分子蛋白，可与多种功能各异的蛋白质相互作用，因此确定其功能缺陷如何导致癌症一直是一大挑战。其中，BARD1蛋白似乎是BRCA1抑癌功能的重要调控因子，其本身也具有抑癌作用。BARD1对细胞存活至关重要，因此功能缺失性突变极为罕见，但可能改变其功能的突变和截短形式或许参与了乳腺癌的发病过程。

原文链接：

Is there more to BARD1 than BRCA1?