Homologs of the yeast longevity gene LAG1 in Caenorhabditis elegans and human
Homologs of the yeast longevity gene LAG1 in Caenorhabditis elegans and human
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DOI：
10.1101/gr.8.12.1259
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发表时间：
1998-12-01
期刊：
影响因子：
7
通讯作者：
Jazwinski, SM
中科院分区：
文献类型：
--
作者：
Jiang, JC;Kirchman, PA;Jazwinski, SM
LAG 1是一个长寿基因，是第一个从酿酒酵母中鉴定和克隆的基因。我们称之为LAC 1的这个基因的一个密切同源物已经在酵母基因组中发现。我们克隆了LAG 1的人类同源物，最终目的是研究其在人类衰老中的可能功能。在这个过程中，我们还克隆了线虫秀丽隐杆线虫的同源物。这两个同源物，LAG 1H和LAG 1Ce-1功能上补充了lag 1 Δ lac 1 Δ双缺失的致死性，尽管与酵母蛋白的整体序列相似性低。蛋白质共享一个短序列，Lag 1基序，和一个类似的跨膜结构域配置文件。另一个更远的人类同源物TRAM缺乏这种基序，没有互补。LAG 1H还恢复了双缺失的寿命，表明它在酵母中建立长寿表型中起作用。LAG 1H定位于19 p12，仅在三种组织中表达：脑、骨骼肌和睾丸。该基因在外显子1内具有三核苷酸（CTG）重复。这一点及其表达谱提高了它可能参与神经退行性疾病的可能性。这种可能性表明LAG 1H可能参与人类衰老的至少一种方式。
LAG1 is a longevity gene, the first such gene to be identified and cloned from the yeast Saccharomyces cerevisiae. A close homolog of this gene, which we call LAC1, has been found in the yeast genome. We have cloned the human homolog of LAG1 with the ultimate,ooal of examining its possible function in human aging. In the process, we have also cloned a homolog from the nematode worm Caenorhabditis elegans. Both of these homologs, LAG1Hs and LAG1Ce-1 functionally complemented the lethality of a lag1 Delta lac1 Delta double deletion, despite low overall sequence similarity to the yeast proteins. The proteins shared a short sequence, the Lag1 motif, and a similar transmembrane domain profile. Another, more distant human homolog, TRAM, which lacks this motif, did not complement. LAG1Hs also restored the life span of the double deletion, demonstrating that it functions in establishing the longevity phenotype in yeast. LAG1Hs mapped to 19p12, and it was expressed in only three tissues: brain, skeletal muscle, and testis. This gene possesses a trinucleotide (CTG) repeat within exon 1. This and its expression profile raise the possibility that it may be involved in neurodegenerative disease. This possibility suggests at least one way in which LAG1Hs might be involved in human aging.