Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, Przybyszewskiego 49 St, 60-355 Poznan, Poland.
Mol Biol Rep. 2011 Jun;38(5):3339-49. doi: 10.1007/s11033-010-0439-x. Epub 2010 Nov 18.
Telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells. Thus, it has become a very promising target for anticancer therapy. The cell proliferative potential can be limited by replication end problem, due to telomeres shortening, which is overcome in cancer cells by telomerase activity or by alternative telomeres lengthening (ALT) mechanism. However, this multisubunit enzymatic complex can be regulated at various levels, including expression control but also other factors contributing to the enzyme phosphorylation status, assembling or complex subunits transport. Thus, we show that the telomerase expression targeting cannot be the only possibility to shorten telomeres and induce cell apoptosis. It is important especially since the transcription expression is not always correlated with the enzyme activity which might result in transcription modulation failure or a possibility for the gene therapy to be overcome. This review summarizes the current state of knowledge of numerous telomerase regulation mechanisms that take place after telomerase subunits coding genes transcription. Thus we show the possible mechanisms of telomerase activity regulation which might become attractive anticancer therapy targets.
端粒酶已被认为是区分癌细胞和正常细胞的相关因素。因此，它已成为癌症治疗的一个非常有前途的靶点。由于端粒缩短，细胞的增殖潜力可能会受到复制末端问题的限制，而癌细胞则通过端粒酶活性或通过替代端粒延长（ALT）机制来克服这个问题。然而，这种多亚基酶复合物可以在多个水平上进行调节，包括表达控制，以及其他因素对酶磷酸化状态、组装或复合物亚基运输的影响。因此，我们表明，端粒酶表达靶向可能不是缩短端粒和诱导细胞凋亡的唯一可能性。这一点很重要，特别是因为转录表达并不总是与酶活性相关，这可能导致转录调节失败，或者基因治疗可能被克服。这篇综述总结了目前对端粒酶编码基因转录后发生的许多端粒酶调节机制的认识。因此，我们展示了端粒酶活性调节的可能机制，这些机制可能成为有吸引力的抗癌治疗靶点。
