Transcriptional coordination of the genes encoding catalytic (CK2α) and regulatory (CK2β) subunits of human protein kinase CK2
Transcriptional coordination of the genes encoding catalytic (CK2α) and regulatory (CK2β) subunits of human protein kinase CK2
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DOI：
10.1023/a:1013152621029
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发表时间：
2001-01-01
影响因子：
4.3
通讯作者：
Ackermann, K
中科院分区：
文献类型：
--
作者：
Pyerin, W;Ackermann, K
蛋白激酶CK2基因是如何调控的知之甚少，也不清楚是否存在转录协调机制。已使用报告基因测定、电泳迁移率变动测定、定点诱变、异位蛋白表达和转录物评估来检查存在于人催化（CK2 α）和调节（CK2 β）亚基基因的启动子序列中的响应元件在转录控制中的意义。最引人注目的是，在这两个启动子的转录活性最高的区域包含两个相邻的，完全相同的和保守的Ets1响应元件，和基序的突变和过度表达的Ets1显着影响转录活性。同样常见的是与Ets1合作的Sp1反应元件，并且Sp1可被CK2全酶磷酸化，但不能被单个CK2 α磷酸化，磷酸化对DNA结合产生负面影响。CK2 α和CK2 β转录水平和mRNA种类的化学计量在培养的细胞中相当恒定，尽管通过增殖和分化的各个阶段进行。这些数据似乎表明，人类基因编码CK2 α和CK2 β的基础上的Ets1双基序共同的两个基因与Sp1基序合作，并服从负反馈控制的基因产物，以下复合成CK2全酶，可以磷酸化Sp1（和Ets1？）从而下调转录并促成观察到的恒定细胞CK2 α和CK2 β转录物的情况。
Little is known of how protein kinase CK2 genes are regulated, and it is unclear whether there are mechanisms of transcriptional coordination. Response elements present in the promoter sequences of the human catalytic (CK2 alpha) and regulatory (CK2 beta) subunit genes have been examined for the significance in transcriptional control using reporter gene assays, electrophoretic mobility shift assays, site-directed mutagenesis, ectopic protein expressions, and transcript assessments. Most strikingly, in both promoters the regions of highest transcriptional activity contain two adjoining, completely identical and conserved Ets1 response elements, and both the mutation of motifs and the overexpression of Ets1 affect significantly transcriptional activity. Also in common are Sp1 response elements that cooperate with Ets1, and Sp1 is phosphorylatable by CK2 holoenzyme but not by individual CK2 alpha, the phosphorylation negatively affecting DNA binding. CK2 alpha and CK2 beta transcript levels and stoichiometries of mRNA species turned out quite constant in cultured cells despite progressing through various stages of proliferation and differentiation. The data seem to indicate transcriptional coordination of the human genes encoding CK2 alpha and CK2 beta based on an Ets1 double motif common to both genes cooperating with Sp1 motifs and amenable to negative feedback control by the gene products which, following complexation into CK2 holoenzyme, could phosphorylate Sp1 (and Ets1 ?) and thus downregulate transcription and contribute to the observed constant cellular CK2 alpha and CK2 beta transcripts situation.