Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain containing protein
Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain containing protein
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DOI：
10.1038/sj.onc.1201110
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发表时间：
1997-06-05
期刊：
影响因子：
8
通讯作者：
Gress, TM
中科院分区：
文献类型：
--
作者：
MuellerPillasch, F;Lacher, U;Gress, TM
在先前的胰腺癌差异表达基因的大规模筛选中，我们发现了一个在胰腺癌中高表达的基因，编码一个具有四个K-同源(KH)结构域的新蛋白，KH-结构域存在于一组RNA结合蛋白中，包括前mRNA结合蛋白(HnRNP)K蛋白和脆性X智力低下基因产物(FMR1)。经荧光原位杂交(FISH)鉴定基因Koc位于7p11.5染色体上，在第6和11染色体上定位了两个假基因，克隆的Koc基因5‘-UTR250个，ORF 1740个，3’-UTR 2168个。Koc富含AU的3‘-非翻译区包含8个AUUA和4个AUUUA重复序列，推导的Koc蛋白含580个氨基酸，其相对分子质量(M-r)约为65000(65K)。Koc转录本在胰腺癌细胞系和胰腺癌组织中高表达，与正常胰腺和慢性胰腺炎组织相比，在其他人类肿瘤组织中也有高水平的表达，由于KH结构域已被证明参与RNA合成和代谢的调节，我们推测Koc可能通过干扰转录和/或转录后过程而参与调节肿瘤细胞的增殖，然而，Koc在人类肿瘤细胞中的确切作用尚不清楚，还有待于阐明。
In a previous large scale screen for differentially expressed genes in pancreatic cancer, we identified a gene highly overexpressed in cancer encoding a novel protein with four K-homologous (KH) domains, KH-domains are found in a subset of RNA-binding proteins, including pre-mRNA-binding (hnRNP)K protein and the fragile X mental retardation gene product (FMR1). By fluorescence in situ hybridization (FISH) the identified gene named koc (KH domain containing protein overexpressed in cancer) was assigned to chromosome 7p11.5, Two pseudogenes were localised on chromosome 6 and 11, The cloned koc cDNA has a 250 bp 5'-UTR, a 1740 bp ORF and a 2168 bp 3'-UTR, The AU-rich 3'-untranslated region of koc contains eight AUUUA and four AUUUUUA reiterated motifs, The deduced koc protein with 580 amino-acids has a relative molecular mass (M-r) of approximately 65 000 (65 K), The koc transcript is highly overexpressed in pancreatic cancer cell lines and in pancreatic cancer tissue as compared to both, normal pancreas and chronic pancreatitis tissue, High levels of expression were as well found in tissue samples of other human tumours, As the KH domain has been shown to be involved in the regulation of RNA synthesis and metabolism, we speculate that koc may assume a role in the regulation of tumour cell proliferation by interfering with transcriptional and or posttranscriptional processes, However, the precise role of koc in human tumour cells is unknown and remains to be elucidated.