School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
Oncogene. 2014 Feb 13;33(7):805-13. doi: 10.1038/onc.2013.60. Epub 2013 Mar 18.
The proteasome is a cellular machine found in the cytosol, nucleus and on chromatin that performs much of the proteolysis in eukaryotic cells. Recent reports show it is enriched at sites of double-stranded DNA breaks (DSBs) in mammalian cells. What is it doing there? This review will address three possibilities suggested by recent reports: in degrading proteins after their ubiquitination at and eviction from chromatin; as a deubiquitinase, specific to the antagonism of ubiquitin conjugates generated as part of the signalling of a DSB; and as a functional component of DNA repair mechanism itself. These findings add complexity to the proteasome as a potential therapeutic target in cancer treatment.
蛋白酶体是一种存在于细胞质、细胞核和染色质中的细胞机器，它在真核细胞中执行大部分蛋白质水解作用。最近的报告显示，它在哺乳动物细胞的双链 DNA 断裂（DSB）部位富集。它在那里做什么？这篇综述将讨论最近的报告提出的三种可能性：在染色质上泛素化和逐出后降解蛋白质；作为一种去泛素化酶，特异性拮抗作为 DSB 信号一部分产生的泛素缀合物；以及作为 DNA 修复机制本身的功能成分。这些发现增加了蛋白酶体作为癌症治疗潜在治疗靶点的复杂性。
