Gli genes in development and cancer
Gli genes in development and cancer
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DOI：
10.1038/sj.onc.1203243
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发表时间：
1999-12-20
期刊：
影响因子：
8
通讯作者：
Joyner, AL
中科院分区：
文献类型：
--
作者：
Matise, MP;Joyner, AL
随着认识到许多原癌基因和肿瘤抑制基因在哺乳动物发育期间表达并具有重要功能，很明显癌症通常涉及正常发育期间使用的遗传途径的不适当激活。已经引起发育和癌症生物学家相当大的兴趣的信号级联涉及分泌蛋白质的Hedgehog（Hh）家族。到目前为止，唯一的转录因子被证明是直接下游的Hh是锌指蛋白Cubitus interruptus（Ci）和Gli，分别在苍蝇和脊椎动物，许多基因和蛋白质参与Hh信号的鉴定主要来自果蝇的遗传和生化研究。Ci通过一组Hh依赖的蛋白质修饰介导Hh信号传导，所述蛋白质修饰改变Ci对Hh靶基因的活性。最近的证据表明脊椎动物Gli蛋白可能受到类似的调节。随着Hh途径基因（包括Gli基因）突变的鉴定，在几种人类发育障碍和癌症中对该途径的兴趣变得更加重要。我们讨论了Gli蛋白如何在脊椎动物发育和癌症中介导Hh信号传导的模型。
With the realization that many proto-oncogenes and tumor suppressor genes are expressed and have important functions during mammalian development, it is clear that cancer often involves the inappropriate activation of genetic pathways used during normal development. A signaling cascade that has been of considerable interest to both developmental and cancer biologists involves the Hedgehog (Hh) family of secreted proteins. To date, the only transcription factors shown to be directly downstream of Hh are the zinc-finger containing proteins Cubitus interruptus (Ci) and Gli, in flies and vertebrates, respectively, The identification of many of the genes and proteins involved in Hh signaling has come largely from genetic and biochemical studies in Drosophila. Ci mediates Hh signaling through a Hh-dependent set of protein modifications that alter the activity of Ci on Hh target genes, Recent evidence suggests vertebrate Gli proteins may be similarly regulated. The interest in this pathway has taken on added importance with the identification of mutations in Hh pathway genes, including Gli genes, in several human developmental disorders and cancers. We discuss models for how Gli proteins mediate Hh signaling in both vertebrate development and cancers.