Deubiquitinating enzymes as novel anticancer targets.
Deubiquitinating enzymes as novel anticancer targets.
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DOI：
10.2217/14796694.3.2.191
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发表时间：
2007-04-01
期刊：
影响因子：
--
通讯作者：
Mattern, Michael R
中科院分区：
文献类型：
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作者：
Nicholson, Benjamin;Marblestone, Jeffrey G;Mattern, Michael R
用单或多泛素标记蛋白质是目前公认的一种多方面和普遍的调节细胞生长和生理的手段。它通过控制几乎所有真核蛋白质的细胞寿命和许多关键蛋白质的细胞定位来实现这一目标。泛素途径的酶以选择性的方式在其靶蛋白上添加（连接酶）或去除（去泛素酶[DUBs]）泛素标签。与激酶及其相应的磷酸酶类似，泛素连接酶和dub已成为积极研究的分子肿瘤药物发现靶点。人类蛋白质组中存在大约79个功能性dub，这表明选择性干预是一种合理的治疗目标，其目的是下调或消除癌基因产物，或者上调或保留肿瘤抑制因子。在接下来的回顾中，我们将对这类令人着迷的调节酶进行描述，并将考虑作为抗癌治疗可行靶点的dub的具体例子。
Tagging proteins with mono- or poly-ubiquitin is now recognized as a multifaceted and universal means of regulating cell growth and physiology. It does so by controlling the cellular lifetime of nearly all eukaryotic proteins and the cellular localization of many critical proteins. Enzymes of the ubiquitin pathway add (ligases) or remove (deubiquitinases [DUBs]) ubiquitin tags to or from their target proteins in a selective fashion. Similarly to the kinases and their corresponding phosphatases, ubiquitin ligases and DUBs have become actively studied molecular oncology targets for drug discovery. Approximately 79 functional DUBs exist in the human proteome, suggesting that selective intervention is a reasonable therapeutic objective, with the goal of downregulating or ablating oncogene products or, alternatively, upregulating or sparing tumor suppressors. In the following review, this fascinating class of regulatory enzymes will be described, and specific examples of DUBs that are viable targets for anticancer therapy will be considered.