CDK8 is a positive regulator of transcriptional elongation within the serum response network.
CDK8 is a positive regulator of transcriptional elongation within the serum response network.
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DOI：
10.1038/nsmb.1752
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发表时间：
2010-02
影响因子：
16.8
通讯作者：
中科院分区：
文献类型：
--
作者：
介体复合物允许转录因子和RNA聚合酶II（RNAPII）之间的通信。CDK 8是在Mediator的一些变体中发现的激酶，其主要特征是转录阻遏物。最近，CDK 8被证明是一种有效的癌蛋白。在这里，我们表明，CDK 8是一个积极的调节基因的血清反应网络，包括几个成员的AP-1和EGR家族的致癌转录因子。机制研究表明，CDK 8不是RNAPII募集或启动子逃逸所必需的。相反，CDK 8耗竭导致携带低磷酸化RNAPII的较慢延伸复合物的出现。CDK 8-介体调节RNAPII延伸复合物组装中的精确步骤，包括P-TEFb和BRD 4的募集。此外，CDK 8-介体与P-TEFb特异性相互作用。因此，我们发现了CDK 8在转录调控中的新作用，这可能有助于其致癌作用。
The Mediator complex allows communication between transcription factors and RNA polymerase II (RNAPII). CDK8, the kinase found in some variants of Mediator, has been characterized mostly as a transcriptional repressor. Recently, CDK8 was demonstrated to be a potent oncoprotein. Here we show that CDK8 is a positive regulator of genes within the serum response network, including several members of the AP-1 and EGR family of oncogenic transcription factors. Mechanistic studies demonstrate that CDK8 is not required for RNAPII recruitment or promoter escape. Instead, CDK8 depletion leads to the appearance of slower elongation complexes carrying hypophosphorylated RNAPII. CDK8-Mediator regulates precise steps in the assembly of the RNAPII elongation complex, including the recruitment of P-TEFb and BRD4. Furthermore, CDK8-Mediator specifically interacts with P-TEFb. Thus, we uncovered a novel role for CDK8 in transcriptional regulation that may contribute to its oncogenic effects.
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DOI：
10.1073/pnas.2035253100
发表时间：
2003-10-14
影响因子：
11.1
作者：
Cantin, GT;Stevens, JL;Berk, AJ
通讯作者：
Berk, AJ
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
16
作者：
Esnault, Cyril;Ghavi-Helm, Yad;Werner, Michel
通讯作者：
Werner, Michel
影响因子：
16
作者：
Ahn, SH;Kim, M;Buratowski, S
通讯作者：
Buratowski, S
影响因子：
16
作者：
Barboric, M;Nissen, RM;Peterlin, BM
通讯作者：
Peterlin, BM