Ets1 is a common element in directing transcription of the α and β genes of human protein kinase CK2
Ets1 is a common element in directing transcription of the α and β genes of human protein kinase CK2
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DOI：
10.1046/j.1432-1327.2001.02219.x
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发表时间：
2001-06-01
期刊：
影响因子：
--
通讯作者：
Pyerin, W
中科院分区：
文献类型：
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作者：
Krehan, A;Schmalzbauer, R;Pyerin, W
蛋白激酶CK 2是一种保守的和重要的Ser/Thr磷酸转移酶，与恶性疾病有各种联系，作为由两个催化活性亚基（CK 2 α和/或CK 2 α ′）和两个调节亚基（CK 2 β）组成的四聚体存在。在增殖和分化的培养细胞中，CK 2 α和CK 2 β转录物的可用性平衡。通过系统性缺失和报告基因测定对人CK 2 β基因的转录活性区进行检查，表明在含有基因转录起始位点1和2的位置-42至14和12至72处具有强启动子活性（位置+1和33），分别在位置-241至-168和123至677处的上游和下游增强子活性，和-241到-261位置的消音器活性。在这些区域中存在的各种转录因子结合基序中，Ets 1和CAAT相关基序被证明是特别重要的，Ets 1用于启动子激活，CAAT相关基序用于增强子激活。此外，还有SP1的贡献。最引人注目的是，代表两个相邻共有基序的Ets 1区域也以完全相同的方式出现在最近表征的CK 2 α基因的启动子中[Krehan，A.，Ansuini，H.，Bocher，O.，Grein，S.，Wirkner，U. & Pyerin，W.（2001）J.Biol.Chem.275，18327-18336]，并且当平行测定时，通过基序突变和Ets 1过表达影响两种CK 2基因的启动子。这些数据强烈支持这一假设，Ets 1作为一个共同的调控元件的CK 2 α和CK 2 β基因参与指导协调转录，并有助于平衡的可用性的成绩单。
Protein kinase CK2 is a conserved and vital Ser/Thr phosphotransferase with various links to malignant diseases, occurring as a tetramer composed of two catalytically active (CK2 alpha and/or CK2 alpha') and two regulatory subunits (CK2 beta). There is balanced availability of CK2 alpha and CK2 beta transcripts in proliferating and differentiating cultured cells. Examination of the human CK2 beta gene for transcriptionally active regions by systematic deletions and reporter gene assays indicates strong promoter activity at positions -42 to 14 and 12 to 72 containing transcription start sites 1 and 2 of the gene (positions +1 and 33), respectively, an upstream and a downstream enhancer activity at positions -241 to -168 and 123 to 677, respectively, and silencer activity at positions -241 to -261. Of the various transcription factor binding motifs present in those regions, Ets1 and CAAT-related motifs turned out to be of particular importance, Ets1 for promoter activation and CAAT-related motifs for enhancer activation. In addition, there are contributions by Sp1. Most strikingly, the Ets1 region representing two adjoining consensus motifs also occurs with complete identity in the recently characterized promoter of the CK2 alpha gene [Krehan, A., Ansuini, H., Bocher, O., Grein, S., Wirkner, U. & Pyerin, W. (2001) J. Biol. Chem. 275, 18327-18336], and affects comparably, when assayed in parallel, the promoters of both CK2 genes, both by motif mutations and by Ets1 overexpression. The data strongly support the hypothesis that Ets1 acts as a common regulatory element of the CK2 alpha and CK2 beta genes involved in directing coordinate transcription and contributing to the balanced availability of transcripts.