Identification and characterization of a novel gene, c1orf109, encoding a CK2 substrate that is involved in cancer cell proliferation.
Identification and characterization of a novel gene, c1orf109, encoding a CK2 substrate that is involved in cancer cell proliferation.
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编码参与癌细胞增殖的 CK2 底物的新基因 c1orf109 的鉴定和表征
DOI：
10.1186/1423-0127-19-49
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发表时间：
2012-05-01
影响因子：
11
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Liu SS;Zheng HX;Jiang HD;He J;Yu Y;Qu YP;Yue L;Zhang Y;Li Y
背景：在本研究中，我们发现了一个新的基因，智人1号染色体ORF 109（c1orf109，GenBank ID：NM_017850.1），它编码CK2的底物。方法：采用双荧光素酶报告基因分析法、染色质免疫沉淀法和EMSA分析法，对预测的启动子区域进行基础转录调控分析，并对预测的蛋白在细胞中的表达模式、亚细胞定位及其在细胞增殖和细胞周期调控中的作用进行分析。通过蛋白质印迹分析评估C10RF109表达。免疫荧光和免疫胶体金技术检测C1ORF109的亚细胞定位。结果：c1orf109基因启动子关键区域内存在两个顺式作用元件，一个TATA盒和一个CAAT盒，这两个元件是c1orf109基因最大转录所必需的。c1orf109基因的5'侧翼区可与特异性转录因子结合，Sp1可能是其中之一。采用蛋白质印迹分析，我们检测到c1orf109在多种癌细胞系中的表达上调。C1ORF109蛋白主要定位于细胞核和细胞质中。此外，我们还发现C1ORF109在体内是一个磷蛋白，在体外可以被蛋白激酶CK2磷酸化。C1ORF109在乳腺癌Hs578T细胞中的外源性表达诱导集落数目和细胞增殖的增加。同时观察到PCNA（增殖细胞核抗原）和cyclinD1表达水平的升高。结论：C1orf109可能是蛋白激酶CK2的下游靶点，参与了乳腺癌细胞增殖的调控。
Background:In the present study we identified a novel gene, Homo Sapiens Chromosome 1 ORF109 (c1orf109, GenBank ID: NM_017850.1), which encodes a substrate of CK2. We analyzed the regulation mode of the gene, the expression pattern and subcellular localization of the predicted protein in the cell, and its role involving in cell proliferation and cell cycle control.Methods:Dual-luciferase reporter assay, chromatin immunoprecipitation and EMSA were used to analysis the basal transcriptional requirements of the predicted promoter regions. C1ORF109 expression was assessed by western blot analysis. The subcellular localization of C1ORF109 was detected by immunofluorescence and immune colloidal gold technique. Cell proliferation was evaluated using MTT assay and colony-forming assay.Results:We found that two cis-acting elements within the crucial region of the c1orf109 promoter, one TATA box and one CAAT box, are required for maximal transcription of the c1orf109 gene. The 5' flanking region of the c1orf109 gene could bind specific transcription factors and Sp1 may be one of them. Employing western blot analysis, we detected upregulated expression of c1orf109 in multiple cancer cell lines. The protein C1ORF109 was mainly located in the nucleus and cytoplasm. Moreover, we also found that C1ORF109 was a phosphoprotein in vivo and could be phosphorylated by the protein kinase CK2 in vitro. Exogenous expression of C1ORF109 in breast cancer Hs578T cells induced an increase in colony number and cell proliferation. A concomitant rise in levels of PCNA (proliferating cell nuclear antigen) and cyclinD1 expression was observed. Meanwhile, knockdown of c1orf109 by siRNA in breast cancer MDA-MB-231 cells confirmed the role of c1orf109 in proliferation.Conclusions:Taken together, our findings suggest that C1ORF109 may be the downstream target of protein kinase CK2 and involved in the regulation of cancer cell proliferation.
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影响因子：
4
作者：
Pinna, LA
通讯作者：
Pinna, LA
影响因子：
64.5
作者：
Loizou, JI;El-Khamisy, SF;Caldecott, KW
通讯作者：
Caldecott, KW
影响因子：
8
作者：
Lebrin, F;Chambaz, EM;Bianchini, L
通讯作者：
Bianchini, L
影响因子：
8
作者：
Trembley, J. H.;Wang, G.;Unger, G.;Slaton, J.;Ahmed, K.
通讯作者：
Ahmed, K.
在自发永生的非整倍性人角质形成细胞系中的正常角质化。
DOI：
10.1083/jcb.106.3.761
发表时间：
1988-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Boukamp P;Petrussevska RT;Breitkreutz D;Hornung J;Markham A;Fusenig NE
通讯作者：
Fusenig NE