CK2 kinase activity but not its binding to CK2 promoter regions is implicated in the regulation of CK2α and CK2β gene expressions
CK2 kinase activity but not its binding to CK2 promoter regions is implicated in the regulation of CK2α and CK2β gene expressions
复制标题
DOI：
10.1007/s11010-013-1782-8
复制
发表时间：
2013-12-01
影响因子：
4.3
通讯作者：
Rother, Karen
中科院分区：
文献类型：
--
作者：
Lupp, Sarah;Gumhold, Catalina;Rother, Karen
蛋白激酶 CK2 是一种普遍存在的丝氨酸/苏氨酸激酶，控制多种关键细胞功能，由催化 α 和 α' 亚基以及非催化 β 亚基组成，形成全酶，例如 CK2(alpha beta)(2)、CK2 alpha alpha'beta(2) 或 CK2(alpha'beta)(2)。此外，有充分的证据表明除了全酶之外还存在单个亚基。虽然 CK2 亚基在蛋白质水平上得到了很好的分析，但对其转录的调控却知之甚少。多种形式的 CK2 亚基的存在引发了关于它们表达的相互调节的问题。在这里，我们分别定义了CK2α和CK2β基因的两个5'上游区域，作为具有启动子活性的序列。我们发现 CK2 α 和 CK2 α' 刺激报告基因构建体的表达，而 CK2 β 则无活性。使用染色质免疫沉淀测定，我们无法检测内源 CK2 亚基与这些启动子序列在体内的结合。然而，事实证明，抑制 CK2 的激酶活性会减弱启动子活性，表明 CK2α 和 CK2α' 可能通过磷酸化反应间接调节其基因表达。因此，我们在此表明(i)在正常生理条件下CK2不与CK2启动子区域结合，并且(ii)CK2激酶活性涉及其自身表达的调节。
Protein kinase CK2, a ubiquitous serine/threonine kinase in control of a variety of crucial cellular functions, is composed of catalytic alpha- and alpha'-subunits and non-catalytic beta-subunits which form holoenzymes such as CK2(alpha beta)(2), CK2 alpha alpha'beta(2), or CK2(alpha'beta)(2). In addition, there is ample evidence for the occurrence of the individual subunits beside the holoenzyme. While the CK2 subunits are well analyzed on the protein level, only little is known about the regulation of their transcription. The existence of multiple forms of CK2 subunits raised the question about a mutual regulation of their expression. Here we defined two 5'-upstream regions of the CK2 alpha and the CK2 beta genes, respectively, as sequences with promoter activities. We found that CK2 alpha and CK2 alpha' stimulated the expression of the reporter constructs whereas, CK2 beta was inactive. Using chromatin immunoprecipitation assays, we were unable to detect binding of endogenous CK2 subunits to these promoter sequences in vivo. However, it turned out that inhibition of the kinase activity of CK2 attenuated the promoter activity indicating that CK2 alpha and CK2 alpha' might regulate their gene expression indirectly by phosphorylation reactions. Thus, we have shown here (i) that under normal physiological conditions CK2 does not bind to CK2 promoter regions and (ii) that the CK2 kinase activity is implicated in the regulation of its own expression.