The promoter for intestinal cell kinase is head-to-head with F-Box 9 and contains functional sites for TCF7L2 and FOXA factors.
The promoter for intestinal cell kinase is head-to-head with F-Box 9 and contains functional sites for TCF7L2 and FOXA factors.
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DOI：
10.1186/1476-4598-9-104
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发表时间：
2010-05-11
期刊：
影响因子：
37.3
通讯作者：
Mayo MW
中科院分区：
文献类型：
--
作者：
Sturgill TW;Stoddard PB;Cohn SM;Mayo MW
肠细胞激酶（ICK; GeneID 22858）是在人类组织中广泛表达的保守的MAPK和CDK样激酶。来自癌症基因组解剖学项目的数据表明，ICK mRNA在癌症中增加，并且其表达与未表征的F-box蛋白FBX 9（GeneID：26268）的mRNA表达相关。ICK和FBX 9基因头对头排列在相反的链上，转录起始位点相隔约3.3 kb。我们假设ICK和FBX 9是由双向启动子控制的癌症中潜在的重要基因。我们评估了来自乳腺癌（AU 565、SKBR 3）、结肠癌（HCT-15、KM 12）和胃癌（AGS）的癌细胞系以及人胚胎肾（HEK 293 T）细胞中基因间区域在两个方向上的启动子活性。在所有这些品系中，基因间片段在两个方向上都有活性，并且ICK启动子活性大于FBX 9启动子活性。从删除和截短的结果定义了一个最小的启动子ICK，并显示，阻遏物和增强子差异调节ICK与FBX 9启动子活性。ICK启动子包含几个FOX家族转录因子的共有基序，当使用BRONSS比较小鼠和人时，这些基序对齐。FOXA 1和FOXA 2使HEK 293 T细胞中最小启动子的荧光素酶活性增加10-20倍。TCF 7 L2（TCF 4）（基因Id：6934）的共有位点也存在于小鼠和人两者中。β-连环蛋白的表达使最小启动子的活性增加约10倍。ICK参考mRNA（NM_014920.3，NM_016513）以低拷贝数表达，并且在一些乳腺癌中增加，使用对两种ICK转录物特异性的10个碱基标签5 '-TCAACCTTAT-3'。ICK和FBX 9从富含GC并含有CpG岛的双向启动子发散转录。ICK的最小启动子含有β-cateinin/TCF 7 L2和FOXA的功能位点。这些数据与已经提出的ICK在某些乳腺癌和结肠癌的发展和增殖或存活中的功能一致。
Intestinal cell kinase (ICK; GeneID 22858) is a conserved MAPK and CDK-like kinase that is widely expressed in human tissues. Data from the Cancer Genome Anatomy Project indicated ICK mRNA is increased in cancer, and that its expression correlated with expression of mRNA for an uncharacterized F-box protein, FBX9 (GeneID: 26268). ICK and FBX9 genes are arranged head-to-head on opposite strands, with start sites for transcription separated by ~3.3 kb. We hypothesized ICK and FBX9 are potentially important genes in cancer controlled by a bidirectional promoter. We assessed promoter activity of the intergenic region in both orientations in cancer cell lines derived from breast (AU565, SKBR3), colon (HCT-15, KM12), and stomach (AGS) cancers, as well as in embryonic human kidney (HEK293T) cells. The intergenic segment was active in both orientations in all of these lines, and ICK promoter activity was greater than FBX9 promoter activity. Results from deletions and truncations defined a minimal promoter for ICK, and revealed that repressors and enhancers differentially regulate ICK versus FBX9 promoter activity. The ICK promoter contains consensus motifs for several FOX-family transcription factors that align when mouse and human are compared using EMBOSS. FOXA1 and FOXA2 increase luciferase activity of a minimal promoter 10-20 fold in HEK293T cells. Consensus sites for TCF7L2 (TCF4) (Gene Id: 6934) are also present in both mouse and human. The expression of β-catenin increased activity of the minimal promoter ~10 fold. ICK reference mRNAs (NM_014920.3, NM_016513) are expressed in low copy number and increased in some breast cancers, using a ten base tag 5'-TCAACCTTAT-3' specific for both ICK transcripts. ICK and FBX9 are divergently transcribed from a bidirectional promoter that is GC-rich and contains a CpG island. A minimal promoter for ICK contains functional sites for β-cateinin/TCF7L2 and FOXA. These data are consistent with functions that have been proposed for ICK in development and in proliferation or survival of some breast and colon cancers.
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DOI：
10.1073/pnas.060025397
发表时间：
2000-04-11
影响因子：
11.1
作者：
Lin, SY;Xia, WY;Hung, MC
通讯作者：
Hung, MC
影响因子：
2.6
作者：
Granadino, B;Arias-de-la-Fuente, C;Rey-Campos, J
通讯作者：
Rey-Campos, J
影响因子：
4.6
作者：
BACUS, SS;KIGUCHI, K;HUBERMAN, E
通讯作者：
HUBERMAN, E
影响因子：
3.8
作者：
GRAHAM, FL;SMILEY, J;NAIRN, R
通讯作者：
NAIRN, R
影响因子：
9.8
作者：
Lahiry, Piya;Wang, Jian;Hegele, Robert A.
通讯作者：
Hegele, Robert A.