The human Y-encoded testis-specific protein interacts functionally with eukaryotic translation elongation factor eEF1A, a putative oncoprotein
The human Y-encoded testis-specific protein interacts functionally with eukaryotic translation elongation factor eEF1A, a putative oncoprotein
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DOI：
10.1002/ijc.23697
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发表时间：
2008-10-01
影响因子：
6.4
通讯作者：
Lau, Yun-Fai Chris
中科院分区：
文献类型：
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作者：
Kido, Tatsuo;Lau, Yun-Fai Chris
睾丸特异性蛋白Y编码（TSPY）是Y染色体上性腺母细胞瘤基因座的推定基因。TSPY在胎儿和成人睾丸的正常生殖细胞中表达，并在肿瘤生殖细胞中异位表达，包括双性人的性腺母细胞瘤、睾丸生殖细胞肿瘤、前列腺癌和其他体细胞癌症。它是TSPY/SET/NAP 1超家族的成员，具有高度保守的结构域，称为SET/NAP结构域。为了探索其在肿瘤发生中的可能作用，我们对胎儿性腺cDNA文库进行了酵母双杂交筛选，并鉴定了翻译延伸因子eEF 1A作为TSPY在SET/NAP结构域的结合伴侣。TSPY和eEF 1A在人乳腺癌生殖细胞中高表达并共定位，提示它们在生殖细胞肿瘤中可能存在相互作用。它们共定位于细胞质中，并且可以从转染的COS 7细胞中共免疫沉淀。值得注意的是，eEF 1A 1和eEF 1A 2都被假定参与各种类型的人类癌症，包括乳腺癌和前列腺癌。TSPY增强了报告基因的蛋白质合成，这是由eEF 1A的过表达增强。TSPY还增加了eEF 1A的核再分布，导致报告基因转录物的平行增加。我们的结果表明，TSPY可以通过与eEF 1As相互作用并通过增强蛋白质合成和基因转录来刺激基因表达来发挥其致癌功能。
Testis-specific protein Y-encoded (TSPY) is the putative gene for the gonacloblastoma locus on the Y chromosome. TSPY is expressed in normal germ cells of fetal and adult testis and ectopically in tumor germ cells, including gonadoblastoma in intersex patients, testicular germ cell tumors, prostate cancer and other somatic cancers. It is a member of the TSPY/SET/NAP1 superfamily and harbors a highly conserved domain, termed SET/NAP domain. To explore its possible role(s) in tumorigenesis, we had performed a yeast two-hybrid screen of a fetal gonadal cDNA library and identified the translation elongation factor eEF1A as a binding partner for TSPY at the SET/NAP domain. TSPY and eEF1A were highly expressed and colocalized in tumor germ cells of human seminoma specimens, suggesting their possible interaction in germ cell tumors. They were colocalized in the cytoplasm and could be co-immunoprecipitated from transfected COS7 cells. Significantly, both eEF1A1 and eEF1A2 have postulated to be involved in various types of human cancer, including breast and prostate cancers. TSPY enhanced protein synthesis of a reporter gene, which was augmented by an overexpression of eEF1A. TSPY also increased the nuclear redistribution of eEF1A, resulting in a parallel increase in reporter gene transcripts. Our results suggest that TSPY could exert its oncogenic function(s) by interacting with eEF1As and stimulating gene expression via its enhancements in protein synthesis and gene transcription.