CATALYTIC SUBUNIT OF THE TELOMERASE GENE HEST2

端粒酶被认为是使非永生化细胞永生化的关键因素。 根据流行的模型，在没有端粒酶的情况下，正常细胞仅具有有限的复制潜力，这表现为它们在延长传代后进入衰老和危机。 端粒酶通常在大多数正常细胞谱系中被抑制，并且其在危机期间的突然表达似乎允许细胞无限增殖能力-永生化的表型。这种特性使恶性细胞克隆能够扩展到临床上可检测到并最终危及生命的大小。 端粒酶催化亚单位基因hTERT最近被克隆。 许多拟议的实验将检查hTERT基因在细胞通过危机并成为永生化时被抑制的机制。 这些实验将集中于与hTERT启动子相互作用的转录因子，包括由myc和E6癌蛋白指定的转录因子，以及影响hTERT表达的机制。 还有其他工作将评估hTERT的异位表达是否能够使正常的人类细胞避免衰老和危机，使它们永生化，并与已知的癌基因合作，导致它们的恶性转化。

The telomerase enzyme has been proposed to represent the key element that allows non-immortalized cells to become immortalized. According to a prevailing model, in the absence of telomerase, normal cells have only a limited replicative potential as manifested by their entrance into senescence and crisis upon extended passage. Telomerase is usually repressed in most normal cell lineages and its sudden expression during crisis appears to allow cells unlimited proliferative ability - the phenotype of immortalization. This trait enables malignant cell clones to expand to a size where they become clinically detectable and ultimately life threatening. hTERT, the gene specifying the catalytic subunit of telomerase, has recently been cloned. Many of the proposed experiments will examine the mechanisms by which the hTERT gene becomes depressed when cells pass through crisis and become immortalized. These experiments will focus on the transcription factors that interact with the hTERT promoter, including those specified by the myc and E6 oncoproteins, and the mechanisms that affect hTERT expression. Yet other work will assess whether whether ectopic expression of hTERT enables normal human cells to avoid senescence and crisis, immortalizes them and, in cooperation with known oncogenes, leads to their malignant transformation.