Cairney C J, Keith W N
Centre for Oncology and Applied Pharmacology, University of Glasgow, Cancer Research UK Beatson Laboratories, Bearsden, Glasgow G61 1BD, UK.
Biochimie. 2008 Jan;90(1):13-23. doi: 10.1016/j.biochi.2007.07.025. Epub 2007 Aug 6.
Telomerase activity is dependent on the expression of 2 main core component genes, hTERT, which encodes the catalytic component and hTR (also called TERC), which encodes the RNA component. The correlation between telomerase activity and carcinogenesis has made this molecule of great interest in cancer research, however in order to fully understand the regulation of telomerase the mechanisms controlling both telomerase genes need to be studied. Some of these mechanisms of regulation have begun to emerge, however many more remain to be deciphered. For many years hTERT has been regarded as the limiting component of telomerase and much of the research in this field has focussed on its regulation, however it was clear from an early stage that hTR expression was also tightly regulated in normal cells and disease. More recently evidence from biochemistry, promoter studies and mouse models has been steadily increasing for a role for hTR as a limiting and essential component for telomerase activity and telomere maintenance. Perhaps the time has come to redefine our view of telomerase regulation. Knowledge of the mechanisms controlling both telomerase genes in normal systems and cancer may aid our understanding of the role of telomerase in carcinogenesis or highlight potential areas for therapeutic intervention. Here we review the essential requirement of hTR for telomere maintenance and telomerase activity in normal tissues and disease and focus on recent advances in our understanding of hTR regulation in relation to hTERT.
端粒酶活性依赖于两个主要核心组成基因的表达，即编码催化成分的hTERT和编码RNA成分的hTR（也称为TERC）。端粒酶活性与致癌作用之间的相关性使得该分子在癌症研究中备受关注，然而，为了全面了解端粒酶的调控机制，需要研究控制这两个端粒酶基因的机制。其中一些调控机制已经开始显现，但仍有许多有待破译。多年来，hTERT一直被视为端粒酶的限制成分，该领域的许多研究都集中在其调控上，然而，从早期就很清楚，hTR的表达在正常细胞和疾病中也受到严格调控。最近，来自生物化学、启动子研究和小鼠模型的证据不断增加，表明hTR作为端粒酶活性和端粒维持的限制和必需成分发挥作用。也许是时候重新定义我们对端粒酶调控的看法了。了解正常系统和癌症中控制这两个端粒酶基因的机制，可能有助于我们理解端粒酶在致癌作用中的作用，或突出潜在的治疗干预领域。在这里，我们综述了hTR在正常组织和疾病中端粒维持和端粒酶活性方面的基本需求，并重点关注我们对hTR与hTERT相关调控的最新认识进展。
