Structure and expression pattern of human ALR, a novel gene with strong homology to ALL-1 involved in acute leukemia and to Drosophila trithorax
Structure and expression pattern of human ALR, a novel gene with strong homology to ALL-1 involved in acute leukemia and to Drosophila trithorax
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DOI：
10.1038/sj.onc.1201211
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发表时间：
1997-07-31
期刊：
影响因子：
8
通讯作者：
Canaani, E
中科院分区：
文献类型：
--
作者：
Prasad, R;Zhadanov, AB;Canaani, E
ALL-1基因通过染色体易位或内部重排参与人类急性白血病。 ALL-1 是三胸果蝇的人类同源物。后者是三胸组（trx-G）基因的成员，与多梳组（Pc-G）基因一起分别充当正调节因子和负调节因子，以确定果蝇的身体结构。我们克隆了一个新的人类基因 ALR，它编码一个巨大的 5262 个氨基酸长的蛋白质，其中包含 SET 结构域、五个 PHD 指、潜在的锌指和一长串被疏水残基（主要是亮氨酸）中断的谷氨酰胺。 SET基序、PDH指、锌指和其他两个区域与ALL-1和TRX的结构域最相似。前两个基序也存在于其他 trx-G 和 Pc-G 蛋白中。 ALR 基因定位于染色体带 12q12-13，与 VDR 基因相邻。该区域涉及与癌症相关的重复和易位。 ALR表达分析表明，其与18 kb长的mRNA类似，与ALL-1一样，在大多数成人组织中表达，包括多种造血细胞，但肝脏除外。早期小鼠胚胎的整体原位杂交表明在多个组织中表达。基于结构和表达模式的相似性，ALR 很可能与 ALL-1 和 trx 发挥相似的作用，尽管其靶基因尚未确定。
The ALL-1 gene is involved in human acute leukemia through chromosome translocations or internal rearrangements. ALL-1 is the human homologue of Drosophila trithorax. The latter is a member of the trithorax group (trx-G) genes which together with the Polycomb group (Pc-G) genes act as positive and negative regulators, respectively, to determine the body structure of Drosophila. We have cloned a novel human gene, ALR, which encodes a gigantic 5262 amino acid long protein containing a SET domain, five PHD fingers, potential zinc fingers, and a very long run of glutamines interrupted by hydrophobic residues, mostly leucine. The SET motif, PDH fingers, zinc fingers and two other regions are most similar to domains of ALL-1 and TRX. The first two motifs are also found in other trx-G and Pc-G proteins. The ALR gene was mapped to chromosome band 12q12-13, adjacent to the VDR gene. This region is involved in duplications and translocations associated with cancer. The analysis of ALR expression showed that its similar to 18 kb long mRNA is expressed, like ALL-1, in most adult tissues, including a variety of hematopoietic cells, with the exception of the liver. Whole mount in situ hybridization to early mouse embryos indicates expression in multiple tissues. Based on similarities in structure and expression pattern, ALR is likely to play a similar role to ALL-1 and trx, although its target genes have yet to be identified.