Expression and genetic analysis of XIAP-associated factor 1 (XAF1) in cancer cell lines
Expression and genetic analysis of XIAP-associated factor 1 (XAF1) in cancer cell lines
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DOI：
10.1006/geno.2000.6364
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发表时间：
2000-11-15
期刊：
影响因子：
4.4
通讯作者：
Korneluk, RG
中科院分区：
文献类型：
--
作者：
Fong, WG;Liston, P;Korneluk, RG
X连锁凋亡抑制蛋白（XIAP）是一种有效的程序性细胞死亡调节剂。XIAP特异性结合并抑制凋亡的关键效应蛋白酶caspase-3、-7和-9的功能。我们最近分离，酵母双杂交筛选，一种新的34 kDa的锌指蛋白，XIAP相关因子1（XAF 1）。XIAP抑制caspase和抗凋亡的能力被过表达的XAF 1阻断。在这里，我们报告的人XAF 1基因的分离和表征。xaf 1基因由7个外显子组成，长度为18 kb。荧光原位杂交分析将xaf 1位点定位在17p13.2，端粒的p53基因。xaf 1基因座进一步细化为YAC 746 C10，距离TP 53约3 cM。使用NCI 60细胞系面板的xaf 1基因座的微卫星分析显示，在所有三个多态性标记测试的杂合性显着降低，表明等位基因缺失的xaf 1基因是普遍存在于癌细胞系。对相同的NCI细胞系组的xaf 1 RNA表达的检查表明，癌细胞系相对于正常人肝脏表现出非常低的mRNA水平。相比之下，XIAP mRNA水平在大多数测试的癌细胞系中相对较高。我们提出，癌细胞中XIAP到XAF 1的高水平表达可能通过XIAP抗凋亡功能的相对增加而提供存活优势。(C)北京大学出版社.
X-linked inhibitor of apoptosis protein (XIAP) is a potent modulator of programmed cell death. XIAP specifically binds and inhibits the function of caspase-3, -7, and -9, key effector proteases of apoptosis. We recently isolated, by yeast two-hybrid screening, a novel 34-kDa zinc finger protein, XIAP-associated factor 1 (XAF1). Both the caspase inhibiting and the anti-apoptotic abilities of XIAP were found to be blocked by overexpressed XAF1. Here, we report the isolation and characterization of the human XAF1 gene. The xaf1 gene consists of seven exons spanning 18 kb. Fluorescence in situ hybridization analysis localized the xaf1 locus at 17p13.2, telomeric to the p53 gene. The xaf1 locus was further refined to YAC 746C10, approximately 3 cM distal to TP53. Microsatellite analysis of the xaf1 locus using the NCI60 cell line panel revealed significantly decreased heterozygosity at all three polymorphic markers tested, suggesting that allelic loss of the xaf1 gene is prevalent in cancer cell lines. Examination of the same NCI cell line panel for xaf1 RNA expression demonstrated that cancer cell lines exhibited very low levels of mRNA relative to normal human liver. In contrast, XIAP mRNA levels were relatively high in the majority of cancer cell lines tested. We propose that a high level of XIAP to XAF1 expression in cancer cells may provide a survival advantage through the relative increase of XIAP anti-apoptotic function. (C) 2000 Academic Press.