Possible new function of telomerase

端粒酶是一种能延长真核细胞染色体末端端粒DNA的酶，为细胞提供无限的增殖寿命。然而，我们的研究结果表明，端粒酶参与更多的端粒酶表达的人类体细胞。一些人的体细胞在体外继续增殖到端粒缩短的极限，并通过细胞衰老停止增殖，但另一些体细胞在端粒缩短之前通过培养休克或过早衰老停止增殖。这些人体细胞在导入T抗原基因后可以增殖到端粒侵蚀的最终末端，T抗原基因的基因产物使肿瘤抑制基因产物如p53和RB失活。出乎意料的是，将端粒酶基因（hTERT）导入人体细胞也延长了增殖寿命，有时使细胞永生（无限增殖寿命）。我们通过蛋白质组学分析，在引入端粒酶的人体细胞中寻找促进细胞持续增殖的细胞蛋白。我们确定了许多蛋白质，通过MAS分析，从2D-凝胶斑点，增加或减少引入hTERT后。这些蛋白质对寿命延长的作用将被研究。端粒酶的另一个可能的作用是基因组的完整性。端粒酶介导的人体细胞对染色体畸变和外源遗传物质的整合具有抗性。这些特征有利于具有端粒酶活性的体干细胞在整个人类寿命期间持续增殖并保持低致瘤性的功能。

Telomerase is known as an enzyme that elongates telomere DNA at each chromosome end of eukaryotic cells providing cells indefinite proliferative lifespan. However, our results suggested that telomerase participated more than that in telomerase-expressing human somatic cells. Some human somatic cells in vitro continue proliferation to the limit of telomere shortening and ceased proliferation by cellular senescence but other somatic cells cease proliferation by culture shock or premature senescence far before telomere shortening. These human somatic cells can proliferate to the final end of telomere erosion after the introduction of T-antigen gene whose gene product inactivates tumor suppressor gene products as p53 and RB. Unexpectedly, introduction of telomerase gene (hTERT) into human somatic cells also extended proliferative lifespan and sometimes made cells immortal (infinite proliferative lifespan). We searched for cellular proteins, by proteome analysis, that facilitated cells for continued proliferation in telomerase introduced human somatic cells. We identified many proteins, by MAS analysis, from 2D-gel spots that were increased or decreased after introduction of hTERT. Role of these proteins on lifespan extension will be examined. Other possible role of telomerase is on genome integrity. Telomerase-introduced human somatic cells showed resistance against chromosome aberration and integration of exogenous genetic materials. These characteristics are favorable for the function of somatic stem cells, which harbor telomerase activity, to continue proliferation during whole human lifespan and to maintain low tumorigenicity.