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端粒酶活性调控所涉及的分子机制

[Molecular mechanisms involved in the regulation of telomerase activity].

作者信息

Liu W J, Ding J

机构信息

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031.

出版信息

Sheng Li Ke Xue Jin Zhan. 2001 Jul;32(3):220-4.

Abstract

The main components of telomerase include RNA subunit, hTERT catalytic subunit and hTEP1 regulatory protein. While telomerase plays an important role in maintenance of telomere structural stability, telomere is also involved in the regulation of telomerase activity. Some anticancer drugs inhibit the telomerase activity by breaking the structure of telomere. Activation of human telomerase requires de novo transcription of hTERT gene and correct incorporation of all subunits into holoenzyme. The expression of telomerase activity is likely to be regulated at multiple levels. Firstly, the expression and transcription of the hTERT gene is regulated by various factors; Secondly, various oncogenes and tumor suppressor genes are involved in regulation of telomerase activity by protein-protein interaction with telomere and telomerase proteins directly or indirectly. Thirdly, phosphorylation of hTERT and hTEP1 by protein kinase leads to significant up-regulation of telomerase activity, and conversely, the dephosphorylation result in down-regulation of telomerase activity.

摘要

端粒酶的主要成分包括RNA亚基、hTERT催化亚基和hTEP1调节蛋白。虽然端粒酶在维持端粒结构稳定性方面发挥着重要作用,但端粒也参与了端粒酶活性的调节。一些抗癌药物通过破坏端粒结构来抑制端粒酶活性。人端粒酶的激活需要hTERT基因的从头转录以及所有亚基正确组装成全酶。端粒酶活性的表达可能在多个水平受到调控。首先,hTERT基因的表达和转录受多种因素调控;其次,各种癌基因和抑癌基因通过与端粒和端粒酶蛋白直接或间接的蛋白质-蛋白质相互作用参与端粒酶活性的调控。第三,蛋白激酶对hTERT和hTEP1的磷酸化导致端粒酶活性显著上调,相反,去磷酸化则导致端粒酶活性下调。

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