Human endogenous retrovirus protein cORF supports cell transformation and associates with the promyelocytic leukemia zinc finger protein
Human endogenous retrovirus protein cORF supports cell transformation and associates with the promyelocytic leukemia zinc finger protein
复制标题
DOI：
10.1038/sj.onc.1203794
复制
发表时间：
2000-09-07
期刊：
影响因子：
8
通讯作者：
Mueller-Lantzsch, N
中科院分区：
文献类型：
--
作者：
Boese, A;Sauter, M;Mueller-Lantzsch, N
人类内源性逆转录病毒序列（HERV）存在于灵长类动物和人类的基因组中数百万年，大多数HERV是非编码的，但有限的一组是完整的并且可以表达蛋白质。我们最近在7号染色体上鉴定了几乎完整的HERV-K（HML-2）前病毒，并且已经证明大多数生殖细胞肿瘤（GCT）患者显示针对HERV-K（HML-2）蛋白的抗体，为了解决这些蛋白质是否仅仅代表肿瘤标志物或有助于肿瘤转化，我们检查了各种HERV序列的转化潜力，并通过酵母双杂交和生物化学测定研究了HERV和细胞蛋白之间的物理相互作用。cORF是由cenv基因C端开放阅读框编码的蛋白质，支持裸鼠肿瘤生长，并与早幼粒细胞白血病锌指蛋白（PLZF）相关。cORF的氨基酸残基21和87之间以及PLZF的氨基酸残基245和543之间的相互作用结构域，PLZF对小鼠精子发生至关重要。精子发生异常或生殖母细胞成熟被认为是人类发生生殖细胞肿瘤的易感因素。因此，人内源性逆转录病毒的cORF可能通过干扰涉及PLZF的精子发生过程而促进肿瘤的发展。
Human endogenous retrovirus sequences (HERVs) reside in the genomes of primates and humans for several million years, The majority of HERVs is non-coding but a limited set is intact and can express proteins, We have recently identified an almost intact HERV-K(HML-2) provirus on chromosome 7 and have documented that most patients with germ cell tumors (GCTs) display antibodies directed against proteins of HERV-K(HML-2), To address whether these proteins merely represent tumor markers or contribute to neoplastic transformation, we examined the transforming potential of various HERV sequences and studied physical interactions between HERV and cellular proteins by yeast two-hybrid and biochemical assays. cORF, a protein encoded by the C-terminal open reading frame within the cnv gene, supports tumor growth in nude mice and associates with the promyelocytic leukemia zinc finger protein (PLZF), The interaction domains map between amino acid residues 21 and 87 of cORF, and between residues 245 and 543 of PLZF, PLZF is critical for spermatogenesis in mice. Abnormal spermatogenesis or maturation of gonocytes is thought to predispose humans to the development of germ cell tumors. Thus, cORF of human endogenous retroviruses may contribute to tumor development by interfering,vith processes during spermatogenesis that involve PLZF.