Wu J, He J, Mountz J D
University of Alabama at Birmingham, Birmingham Veterans Administration Medical Center, 35294-0007, USA.
Mech Ageing Dev. 1998 Jun 1;103(1):27-44. doi: 10.1016/s0047-6374(98)00008-6.
Werner's syndrome (WS) is an inherited disease with clinical symptoms which resemble premature aging. The Werner's syndrome gene (WRN), which is located on human chromosome 8p12, encodes a predicted protein of 1432 amino acids and shows significant similarity to DNA helicases. We have cloned the full-length mouse cDNA homologue of the human WRN gene encoding a predicted protein of 1320 amino acids and have obtained a full-length 70 kb genomic clone containing the moWRN gene. This gene has been mapped to chromosome 8A3 in mice. The expression of the moWRN gene was increased during apoptosis after IL-2 deprivation, and decreased in the spleen of aged mice. Lymphoid cells isolated from a patient with WS exhibited increased apoptosis after incubation with anti-Fas but not after incubation with the topoisomerase inhibitor VP16. RNase protection reviled dysregulation of the ICE family of apoptosis molecules in the WS cell line. These results indicate that the WS helicase is involved in certain pathways of apoptosis, and defective WS gene expression leads to accumulation of cells that are highly susceptibility to Fas-induced apoptosis.
沃纳综合征（WS）是一种遗传性疾病，其临床症状类似于早衰。位于人类染色体8p12上的沃纳综合征基因（WRN）编码一种预测有1432个氨基酸的蛋白质，与DNA解旋酶具有显著相似性。我们克隆了人类WRN基因的全长小鼠cDNA同源物，其编码一种预测有1320个氨基酸的蛋白质，并获得了一个包含moWRN基因的全长70 kb基因组克隆。该基因已定位到小鼠的8A3染色体上。moWRN基因的表达在IL-2剥夺后的细胞凋亡过程中增加，而在老年小鼠的脾脏中减少。从一名WS患者分离的淋巴细胞在与抗Fas孵育后凋亡增加，但与拓扑异构酶抑制剂VP16孵育后则无此现象。核糖核酸酶保护分析揭示了WS细胞系中凋亡分子ICE家族的失调。这些结果表明，WS解旋酶参与了某些凋亡途径，而有缺陷的WS基因表达导致对Fas诱导凋亡高度敏感的细胞积累。
