Fisher Robert P
Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
J Cell Sci. 2005 Nov 15;118(Pt 22):5171-80. doi: 10.1242/jcs.02718.
In metazoans, cyclin-dependent kinase 7 (CDK7) has essential roles in both the cell-division cycle and transcription, as a CDK-activating kinase (CAK) and as a component of the general transcription factor TFIIH, respectively. Controversy over its double duty has been resolved, but questions remain. First, how does CDK7 achieve the dual substrate specificity necessary to perform both roles? Second, is there a deeper connection implied by the dichotomy of CDK7 function, for example similar mechanisms controlling cell division and gene expression, and/or actual coordination of the two processes? Enzymological studies have revealed solutions to the unusual substrate recognition problem, and there is evidence that the distinct functions of CDK7 can be regulated independently. Finally, despite divergence in their wiring, the CAK-CDK networks of budding yeast, fission yeast and metazoans all link transcriptional regulation with operation of the cell-cycle machinery. This connection might help to ensure that mRNAs encoding effectors of cell division are expressed at the right time in the cycle.
在多细胞动物中，细胞周期蛋白依赖性激酶7（CDK7）在细胞分裂周期和转录过程中都发挥着重要作用，分别作为细胞周期蛋白依赖性激酶激活激酶（CAK）和通用转录因子TFIIH的一个组成部分。关于其双重作用的争议已经得到解决，但问题仍然存在。首先，CDK7如何实现履行这两种作用所需的双重底物特异性？其次，CDK7功能的二分法是否暗示着更深层次的联系，例如控制细胞分裂和基因表达的相似机制，和/或这两个过程的实际协调？酶学研究已经揭示了针对这种异常底物识别问题的解决方案，并且有证据表明CDK7的不同功能可以独立调节。最后，尽管出芽酵母、裂殖酵母和多细胞动物的CAK-CDK网络在连接方式上存在差异，但它们都将转录调控与细胞周期机制的运行联系起来。这种联系可能有助于确保编码细胞分裂效应器的mRNA在细胞周期的正确时间表达。
