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Possible new function of telomerase

端粒酶可能的新功能

基本信息

批准号：
14370745
负责人：
IDE Toshinori
金额：
$ 8.9万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

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.

端粒酶是一种延长真核细胞每条染色体末端端粒DNA的酶，为细胞提供无限期的增殖寿命。然而，我们的研究结果表明，端粒酶在表达端粒酶的人体细胞中发挥了更多的作用。一些体细胞在体外继续增殖到端粒缩短的极限，并因细胞衰老而停止增殖，而另一些体细胞在端粒缩短之前就因培养冲击或过早衰老而停止增殖。在引入t抗原基因后，这些人体细胞可以增殖到端粒侵蚀的最后一端，其基因产物灭活肿瘤抑制基因产物p53和RB。意想不到的是，将端粒酶基因（hTERT）引入人体体细胞，也延长了细胞的增殖寿命，有时甚至使细胞永生（无限增殖寿命）。通过蛋白质组分析，我们寻找能够促进端粒酶引入的人类体细胞中细胞持续增殖的细胞蛋白。通过MAS分析，我们从引入hTERT后增加或减少的2d凝胶点中鉴定出许多蛋白质。这些蛋白质在延长寿命中的作用将被研究。端粒酶的另一个可能的作用是保持基因组的完整性。端粒酶引入的人体细胞表现出对染色体畸变和外源遗传物质整合的抗性。这些特点有利于具有端粒酶活性的体细胞干细胞在人的一生中持续增殖和保持低致瘤性。