Telomerase enzyme activation and human cell immortalization
Telomerase enzyme activation and human cell immortalization
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DOI：
10.1016/s0378-4274(98)00278-1
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发表时间：
1998-12-28
影响因子：
3.5
通讯作者：
Meyerson, M
中科院分区：
文献类型：
--
作者：
Meyerson, M
端粒酶（一种合成线性真核染色体端粒末端的酶）的活性在大多数正常人类体细胞中受到抑制，但在大多数人类癌症中被诱导。缺乏端粒酶活性的正常人类细胞会逐渐丢失端粒序列。相比之下，大多数永生化细胞系和人类恶性肿瘤似乎通过端粒酶活性维持恒定的端粒长度。端粒酶由至少两个亚基组成，一个是端粒合成模板的RNA亚基，另一个是催化蛋白亚基。最近首先在酵母和纤毛虫中，然后在人类中，鉴定了编码端粒酶催化蛋白亚基的基因。该催化亚基属于逆转录酶家族。端粒酶亚基的研究进一步明确了端粒酶在控制哺乳动物细胞寿命中的作用。人类端粒酶催化亚基基因 hTERT 在永生化细胞和原发性肿瘤中被诱导表达。当hTERT在迄今为止端粒酶阴性的细胞中异位表达时，端粒酶活性出现，并且在一些细胞中观察到寿命延长。相比之下，小鼠端粒酶RNA亚基基因mTERC的破坏会导致细胞增殖延迟失败。因此，端粒酶活性似乎对于哺乳动物细胞的延长存活是必要的。 (C) 1998 Elsevier Science Ireland Ltd. 保留所有权利。
Activity of telomerase, the enzyme that synthesizes the telomere ends of linear eukaryotic chromosomes, is repressed in most normal human somatic cells but induced in most human cancers. Normal human cells that lack telomerase activity progressively lose telomere sequences. In contrast, most immortalized cell lines and malignant human tumors appear to maintain constant telomere length via telomerase activity. Telomerase is composed of at least two subunits, an RNA subunit that templates telomere synthesis, and a catalytic protein subunit. The gene encoding the catalytic protein subunit of telomerase has recently been identified, first in yeast and ciliates and then in humans. This catalytic subunit belongs to the reverse transcriptase family. Studies of telomerase subunits further define a role for telomerase in the control of mammalian cell lifespan. The expression of the human telomerase catalytic subunit gene, hTERT, is induced in immortalized cells and primary tumors. When hTERT is ectopically expressed in hitherto telomerase-negative cells, telomerase enzyme activity appears, and an extended lifespan has been observed in some cells. In contrast, disruption of the mouse telomerase RNA subunit gene, mTERC, results in a delayed failure of cell proliferation. Telomerase activity therefore appears to be necessary for the prolonged survival of mammalian cells. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.