端粒酶激活机制研究进展

随着对端粒和端粒酶在衰老和肿瘤中重要性认识的不断深入，端粒酶的激活途径已日益成为这一研究领域的热点.已发现，MYC原癌蛋白(myelocytomatosis virus oncoprotein, MYC)在端粒酶的激活中起关键作用.它可以与TERT基因启动子区域内的E盒结合反式直接激活端粒酶，还可能介导了细胞内其他分子如人乳头瘤病毒E6癌蛋白(human papillomavirus E6 oncoprotein, HPV-E6)和雌激素等对端粒酶的激活.雌激素也可与雌激素受体形成复合物,直接与TERT基因启动子区域内的退化雌激素反应元件结合反式激活端粒酶.此外，腺瘤样结肠息肉癌蛋白(adenomatous polyposis coli protein,APC)、p53及调节蛋白质磷酸化和去磷酸化过程的酶类等亦可能参与了端粒酶活性的激活.

Progress on Mechanism of Telomerase Activation

Following the importances of telomere and telomerase in senescence and tumor were recognized, the pathway of telomerase activation is becoming the focus of this area. By now, MYC was found to play key role in telomerase activation. It could activate telomerase directly by binding to E-box in promoter region of TERT gene. At the same time, MYC might mediate other molecules to activate telomerase, such as HPV-E6 and estrogen. Estrogen could activate telomerase directly by forming estrogen/estrogen receptor complex binding to imperfect palindromic degenerate estrogen-responding element in promoter region of TERT gene. APC, p53 and protein phosphorylation might also involve in telomerase activation.