Satyanarayana Ande, Manns Michael P, Rudolph K Lenhard
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Cell Cycle. 2004 Sep;3(9):1138-50. Epub 2004 Sep 10.
Maintenance of functional telomeres, the highly complex nucleo-protein structures, at the end of linear eukaryotic chromosomes appears to be essential for growth and survival of the cells. The compelling correlation between telomerase reactivation and cellular immortalization led to the idea that inhibition of telomerase may provide a way for effective hindrance of cancer cell growth by interfering with telomere maintenance. In addition to targeting the components of telomerase enzyme directly to prevent telomere synthesis, several approaches including disruption of telomeres, interference with telomerase component assembly, translocation of the catalytic component of telomerase have also been under extensive investigation due to the advances in understanding the biology of telomeres and telomerase in recent years. This review will focus on the so far identified approaches to prevent cancer cell growth by targeting telomerase and telomeres with a brief introduction about structure and function of telomeres and telomerase.
功能性端粒是线性真核染色体末端高度复杂的核蛋白结构,维持端粒对于细胞的生长和存活似乎至关重要。端粒酶重新激活与细胞永生化之间令人信服的关联引发了这样一种观点,即抑制端粒酶可能为通过干扰端粒维持来有效阻碍癌细胞生长提供一种方法。除了直接靶向端粒酶的成分以阻止端粒合成外,近年来随着对端粒和端粒酶生物学认识的进展,包括破坏端粒、干扰端粒酶成分组装、端粒酶催化成分易位等几种方法也在广泛研究中。本综述将重点介绍迄今为止已确定的通过靶向端粒酶和端粒来阻止癌细胞生长的方法,并简要介绍端粒和端粒酶的结构与功能。