Telomerase is controlled by protein kinase Cα in human breast cancer cells
Telomerase is controlled by protein kinase Cα in human breast cancer cells
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DOI：
10.1074/jbc.273.50.33436
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发表时间：
1998-12-11
影响因子：
4.8
通讯作者：
Liu, JP
中科院分区：
文献类型：
--
作者：
Li, H;Zhao, LL;Liu, JP
端粒酶是一种特异性的RNA指导的DNA聚合酶，其延伸真核细胞染色体的端粒，在人体组织中被抑制，并且在大多数人类癌症的肿瘤进展期间被激活。迄今为止，对端粒酶在癌症中如何被激活和控制知之甚少，尽管激活被认为与癌细胞永生化有关。在这里，我们报告说，人端粒酶相关蛋白1（hTEP1）和端粒酶催化亚基（人端粒酶逆转录酶（hTERT））是磷蛋白，它们的磷酸化是在完整的人乳腺癌细胞端粒酶激活的先决条件。通过hTEP1肽亲和层析鉴定，蛋白激酶C α介导hTEP1和hTERT的磷酸化，并诱导端粒酶活性显著增加。因此，蛋白激酶C α对hTEP1和hTERT的磷酸化代表了在人类癌症中启动和维持端粒酶活性的功能性端粒酶复合物的产生中的重要步骤。
Telomerase, a specialized RNA-directed DNA polymerase that extends telomeres of eukaryotic chromosomes, is repressed in human somatic tissues and becomes activated during tumor progression in most human cancers. To date, little is known about how telomerase is activated and controlled in cancer, although activation is thought to be involved in cancer cell immortalization. Here, we report that human telomerase-associated protein 1 (hTEP1) and the telomerase catalytic subunit (human telomerase reverse transcriptase (hTERT)) are phosphoproteins and that their phosphorylation is a prerequisite for the activation of telomerase in intact human breast cancer cells. Identified by hTEP1 peptide affinity chromatography, protein kinase C alpha mediates the phosphorylation of hTEP1 and hTERT and induces a marked increase in telomerase activity. Thus, phosphorylation of hTEP1 and hTERT by protein kinase C alpha represents an essential step in the generation of a functional telomerase complex in the initiation and maintenance of telomerase activity in human cancer.