【摘要】 人端粒酶由RNA亚基、hTERT催化亚基和hTEP1调节蛋白等组成。端粒酶对端粒结构的稳定起着重要的作用 ,而端粒结构和端粒结合蛋白也影响端粒酶活性。某些化疗药物通过破坏端粒结构下调端粒酶活性。端粒酶的激活需要hTERT基因的从头转录和各个蛋白亚基正确装配为端粒酶全酶。端粒酶活性调节的分子机制包括 :(1)TERT基因的表达和转录是决定端粒酶活性的重要环节 ,受多种因素调控 ;(2 )蛋白激酶Cα和蛋白激酶B磷酸化端粒酶蛋白而激活端粒酶 ,蛋白磷酸酯酶 2A(PP2A)可逆转这一过程 ,下调端粒酶活性 ;(3)多种癌基因和抑癌基因及其编码的蛋白质也直接或间接与端粒蛋白、端粒酶蛋白反应 ,参与端粒酶活性的调控。更多还原

【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.更多还原