The role of PRDMs in cancer: one family, two sides
The role of PRDMs in cancer: one family, two sides
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DOI：
10.1016/j.gde.2016.03.009
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发表时间：
2016-02-01
影响因子：
4
通讯作者：
Guccione, Ernesto
中科院分区：
文献类型：
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作者：
Mzoughi, Slim;Tan, Ying Xim;Guccione, Ernesto
PRDM蛋白家族具有一个独特的结构，具有一个N-末端的PR结构域，它具有潜在的甲基转移酶活性，随后在C-末端有不同数量的锌指，可能介导蛋白质-蛋白质、蛋白质-RNA或蛋白质-DNA的相互作用。有趣的是，尽管没有全面的功能数据，但在多种癌症类型中，所有家庭成员都与缺失、突变、表观遗传沉默或过度表达有关。有趣的是，几乎所有的PRDM家族成员都存在不同的亚型。这些异构体不仅受到不同的调控，而且在癌症中扮演着相反的角色，在被称为“阴阳”调控的过程中，这类表观遗传调控是典型的。总而言之，这些发现为未来的干预奠定了基础，通过直接针对其内在的催化活性，或间接地，差异调节肿瘤抑制物/癌基因异构体表达的途径。
The PRDM family of proteins share a unique structure, with an N-terminal PR domain, which has a potential methyltransferase activity, followed by a distinct number of zinc fingers at the C-terminus, potentially mediating protein-protein, protein-RNA or protein-DNA interactions. Interestingly, despite no comprehensive functional data, all family members have been associated with deletions, mutations, epigenetic silencing or overexpression, in multiple cancer types. The intriguing observation is that different isoforms exist for almost all PRDM family members. These isoforms are not only differentially regulated, but play opposite roles in cancer, in what has been termed 'Yin and Yang' regulation, typical of this class of epigenetic regulators. Collectively, these findings set the stage for future intervention, by targeting directly their intrinsic catalytic activities, or indirectly, pathways that differentially regulate tumor suppressor/oncogenic isoform-expression.