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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >CLONING AND CHARACTERIZATION OF A CELLULAR APOPTOSIS SUSCEPTIBILITY GENE, THE HUMAN HOMOLOGUE TO THE YEAST CHROMOSOME SEGREGATION GENE CSE1
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CLONING AND CHARACTERIZATION OF A CELLULAR APOPTOSIS SUSCEPTIBILITY GENE, THE HUMAN HOMOLOGUE TO THE YEAST CHROMOSOME SEGREGATION GENE CSE1

机译:细胞凋亡易感基因的克隆与鉴定,酵母染色体分离基因CSE1的人类同源性

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We recently isolated human cDNA fragments that render MCF-7 breast cancer cells resistant to cell death caused by Pseudomonas exotoxin, Pseudomonas exotoxin-derived immunotoxins, diphtheria toxin, and tumor necrosis factor. We report here that one of these fragments is an antisense fragment of a gene homologous to the essential yeast chromosome segregation gene CSE1. Cloning and analysis of the full-length cDNA of the human CSE1 homologue, which we name CAS for cellular apoptosis susceptibility gene, reveals a protein coding region with similar length (971 amino acids for CAS, 960 amino acids for CSE1) and 59% overall protein homology to the yeast CSE1 protein. The conservation of this gene indicates it has an important function in human cells consistent with the essential role of CSE1 in yeast. CAS is highly expressed in human tumor cell fines and in human testis and fetal liver, tissues that contain actively dividing cells. Furthermore, CAS expression increases when resting human fibroblasts are induced to proliferate and decreases when they are growth-arrested. Thus, CAS appears to play an important role in both toxin and tumor necrosis factor-mediated cell death, as well as in cell proliferation. [References: 16]
机译:我们最近分离了人类cDNA片段,这些片段使MCF-7乳腺癌细胞对由假单胞菌外毒素,假单胞菌外毒素衍生的免疫毒素,白喉毒素和肿瘤坏死因子引起的细胞死亡具有抗性。我们在这里报告这些片段之一是与必需酵母染色体分离基因CSE1同源的基因的反义片段。人CSE1同源基因的全长cDNA的克隆和分析(我们将CAS称为细胞凋亡易感性基因)揭示了一个具有相似长度的蛋白质编码区(CAS的971个氨基酸,CSE1的960个氨基酸),总体占59%蛋白与酵母CSE1蛋白同源。该基因的保守性表明它在人细胞中具有重要作用,与酵母中CSE1的基本作用相一致。 CAS在人类肿瘤细胞细粉以及人类睾丸和胎儿肝脏(含有活跃分裂细胞的组织)中高度表达。此外,当诱导静息的人类成纤维细胞增殖时,CAS表达增加,而当其被抑制生长时,CAS表达降低。因此,CAS似乎在毒素和肿瘤坏死因子介导的细胞死亡以及细胞增殖中均起重要作用。 [参考:16]

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