THE GLI GENE IS A MEMBER OF THE KRUPPEL FAMILY OF ZINC FINGER PROTEINS
THE GLI GENE IS A MEMBER OF THE KRUPPEL FAMILY OF ZINC FINGER PROTEINS
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DOI：
10.1038/332371a0
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发表时间：
1988-03-24
期刊：
影响因子：
64.8
通讯作者：
VOGELSTEIN, B
中科院分区：
文献类型：
--
作者：
KINZLER, KW;RUPPERT, JM;VOGELSTEIN, B
许多研究已经证实，在癌症中，正常细胞中的一部分基因会因点突变、转位或基因扩增而发生改变。然而，绝大多数发生在肿瘤细胞中的遗传变化尚未被确定。为了确定这些其他的基因变化，我们最近通过在人类胶质母细胞瘤2中扩增，分离出了一个基因，GLI。随后，glis在其他人类胶质母细胞瘤中被发现扩增（参考文献3和未发表的数据）。为了更好地了解glii在人类肿瘤中的作用，我们克隆了glii互补DNA （cDNA）并确定了其核苷酸序列。对预测翻译产物的分析表明，它含有最初在xenopu转录因子III a (TFIIIA)4中描述的DNA结合一致序列（锌指）的5个重复。此外，这些锌指含有序列元素，表明gligene产物是最近描述的锌指蛋白kruppel家族的成员5,6。进一步的实验表明，gliis是一种进化保守基因，在胚胎癌细胞中表达，但在大多数成人组织中不表达。考虑到发育中的胚胎组织和肿瘤组织之间的相似性，发育中重要的Kruppel基因家族和glis之间的联系是有趣的。
Many studies have established that a select subset of normal cellular genes are altered in cancer by point mutations, translo-cations or gene amplification1. However, the vast majority of genetic changes that occur in neoplastic cells have not yet been identified. In an attempt to identify some of these other genetic changes, we have recently isolated a gene,GLI, by virtue of its amplification in a human glioblastoma2. Subsequently,GLIwas found to be amplified in other human glioblastomas (ref. 3 and unpublished data). To understand better the role ofGLIin human neoplasia, we have now cloned theGLIcomplementary DNA (cDNA) and determined its nucleotide sequence. Analysis of the predicted translation product reveals that it contains five repeats of a DNA binding consensus sequence (zinc finger) originally described inXenopusTranscription Factor III A (TFIIIA)4. Furthermore, these zinc fingers contain sequence elements that suggest theGLIgene product is a member of the recently describedKruppelfamily of zinc finger proteins5,6. Additional experiments demonstrate thatGLIis an evolutionary conserved gene that is expressed in embryonal carcinoma cells but not in most adult tissues. The link between the developmentally important Kruppel family of genes andGLIis interesting considering the similarities between developing embryonic and neoplastic tissue.