BRCA1-mediated ubiquitylation
BRCA1-mediated ubiquitylation
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DOI：
10.4161/cc.5.14.2930
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发表时间：
2006-07-15
期刊：
影响因子：
4.3
通讯作者：
Boulton, Simon J.
中科院分区：
文献类型：
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作者：
Boulton, Simon J.
BRCA 1肿瘤抑制因子及其异源二聚体伴侣BARD 1在协调细胞对DNA损伤的反应中发挥关键作用。证据还表明这些蛋白质参与转录调控、细胞周期进程和减数分裂性染色体失活，但它们的作用模式仍然难以捉摸。BRCA 1/BARD 1异源二聚体构成E3-泛素（Ub）连接酶的证明提出了特定靶点的泛素化可能允许BRCA 1/BARD 1影响不同细胞过程的可能性。很明显，BRCA 1/BARD 1的E3-Ub连接酶活性具有关键的功能重要性，因为已经鉴定了消除该活性的肿瘤来源的BRCA 1突变。最近的工作和数据表明，BRCA 1/BARD 1功能在C.优雅事实上，在C.线虫和人类细胞已经阐明了E3-泛素（Ub）连接酶活性是如何响应DNA损伤而被调节的。然而，BRCA 1依赖性泛素化的真正靶点尚不清楚，它们的鉴定对于理解BRCA 1在肿瘤发生中的作用仍然至关重要。
The BRCA1 tumour suppressor and its heterodimeric partner BARD1 play crucial roles in coordinating cellular responses to DNA damage. Evidence also implicates these proteins in transcriptional regulation, cell cycle progression and meiotic sex chromosome inactivation, but their mode of action remains elusive. The demonstration that the BRCA1/BARD1 heterodimer constitutes an E3-ubiquitin (Ub) ligase raises the possibility that ubiquitylation of specific targets may allow BRCA1/BARD1 to impact on diverse cellular processes. It is clear that the E3-Ub ligase activity of BRCA1/BARD1 is of critical functional importance as tumour-derived BRCA1 mutations have been identified that eliminate this activity. Recent work and data presented here indicates that BRCA1/BARD1 function is largely conserved in C. elegans. Indeed, studies in C. elegans and human cells have illuminated how the E3-ubiquitin (Ub) ligase activity is regulated in response to DNA damage. However, bone fide targets for BRCA1-dependent ubiquitylation are not known and their identification remains critical to the understanding of the role of BRCA1 in tumorigenesis.