CLONING AND CHARACTERIZATION OF A CELLULAR APOPTOSIS SUSCEPTIBILITY GENE, THE HUMAN HOMOLOG TO THE YEAST CHROMOSOME SEGREGATION GENE CSE1
CLONING AND CHARACTERIZATION OF A CELLULAR APOPTOSIS SUSCEPTIBILITY GENE, THE HUMAN HOMOLOG TO THE YEAST CHROMOSOME SEGREGATION GENE CSE1
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DOI：
10.1073/pnas.92.22.10427
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发表时间：
1995-10-24
影响因子：
11.1
通讯作者：
PASTAN, I
中科院分区：
文献类型：
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作者：
BRINKMANN, U;BRINKMANN, E;PASTAN, I
我们最近分离了人类 cDNA 片段，使 MCF-7 乳腺癌细胞能够抵抗假单胞菌外毒素、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。我们在此报道，这些片段之一是与酵母必需染色体分离基因 CSE1 同源的基因的反义片段。对人类 CSE1 同源物（我们将其命名为 CAS，即细胞凋亡易感基因）的全长 cDNA 进行克隆和分析，揭示了与酵母 CSE1 蛋白具有相似长度（CAS 971 个氨基酸，CSE1 960 个氨基酸）和 59% 总体蛋白同源性的蛋白质编码区。该基因的保守性表明它在人类细胞中具有重要的功能，这与 CSE1 在酵母中的重要作用一致。 CAS 在人类肿瘤细胞细粒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，当静息的人成纤维细胞被诱导增殖时，CAS 表达增加；当它们生长停滞时，CAS 表达减少。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发挥着重要作用。
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.