Cloning and transcriptional regulation of genes responsible for synthesis of Gangliosides

被引:21
作者
Zeng, Guichao [1 ]
Yu, Robert K. [1 ]
机构
[1] Med Coll Georgia, Inst Mol Med & Genet, Dev Neurobiol Program, Augusta, GA 30912 USA
关键词
glycosyltransferase; ganglioside; ganglioside synthase; gene cloning; transcription regulation; transcription factors;
D O I
10.2174/138945008783954925
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Ganglioside synthases are glycosyltransferases involved in the biosynthesis of glycoconjugates. A number of ganglioside synthase genes have been cloned and characterized. They are classified into different families of glycosyltransferases based on similarities of their amino acid sequences. Tissue-specific expression of these genes has been analyzed by hybridization using cDNA fragments. Enzymatic characterization with the expressed recombinant enzymes showed these enzymes differ in their donor and acceptor substrate specificities and other biochemical parameters. In vitro enzymatic analysis also showed that one linkage can be synthesized by multiple enzymes and one enzyme may be responsible for synthesis of multiple gangliosides. Following the cloning of the ganglioside synthase genes, the promoters of the key synthase genes in the ganglioside biosynthetic pathway have been cloned and analyzed. All of the promoters are TATA-less, lacking a CCAAT box but containing GC-rich boxes, characteristic of the house-keeping genes, although transcription of ganglioside synthase genes is subject to complex developmental and tissue-specific regulation. A set of cis-acting elements and transcription factors, including Sp1, AP2, and CREB, function in the proximal promoters. Negative-regulatory regions have also been defined in most of the promoters. We present here an overview of these genes and their transcriptional regulation.
引用
收藏
页码:317 / 324
页数:8
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