Zhao J Q, Glasspool R M, Hoare S F, Bilsland A, Szatmari I, Keith W N
CRC Department of Medical Oncology, University of Glasgow, CRC Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
Neoplasia. 2000 Nov-Dec;2(6):531-9. doi: 10.1038/sj.neo.7900114.
Expression of the human telomerase RNA component gene, hTERC is essential for telomerase activity. The hTERC gene is expressed during embryogenesis and then downregulated during normal development, leaving most adult somatic cells devoid of hTERC expression. During oncogenesis, however, hTERC is re-expressed consequently contributing to the unrestricted proliferative capacity of many human cancers. Thus the identification of the molecular basis for the regulation of the telomerase RNA component gene in normal cells and its deregulation in cancer cells is of immediate interest. We have previously cloned the hTERC promoter and in this study have identified several transcription factors that modulate the expression of hTERC. We demonstrate that NF-Y binding to the CCAAT region of the hTERC promoter is essential for promoter activity. Sp1 and the retinoblastoma protein (pRb) are activators of the hTERC promoter and Sp3 is a potent repressor. These factors appear to act in a species-specific manner. Whereas Sp1 and Sp3 act on the human, bovine, and mouse TERC promoters, pRb activates only the human and bovine promoter, and NF-Y is only essential for the human TERC gene.
人端粒酶RNA组分基因（hTERC）的表达对端粒酶活性至关重要。hTERC基因在胚胎发育过程中表达，随后在正常发育过程中下调，导致大多数成人体细胞缺乏hTERC表达。然而，在肿瘤发生过程中，hTERC会重新表达，从而导致许多人类癌症具有不受限制的增殖能力。因此，确定正常细胞中端粒酶RNA组分基因调控的分子基础及其在癌细胞中的失调情况备受关注。我们之前克隆了hTERC启动子，在本研究中鉴定了几种调节hTERC表达的转录因子。我们证明，NF-Y与hTERC启动子的CCAAT区域结合对启动子活性至关重要。Sp1和视网膜母细胞瘤蛋白（pRb）是hTERC启动子的激活剂，而Sp3是一种有效的抑制剂。这些因子似乎以物种特异性的方式发挥作用。Sp1和Sp3作用于人、牛和小鼠的TERC启动子，而pRb仅激活人和牛的启动子，NF-Y仅对人TERC基因至关重要。
