The Other Activities of Telomerase

Telomerase extends telomeres, the protective ends of chromosomes. A portion is lost with each cell division, and this mechanism forms part of a clock regulating the replicative life span of ordinary cells. Stem cells maintain long telomeres and when active work to introduce into tissues a continual supply of new daughter cells with long telomeres. Average telomere length declines with illness or age most likely largely because of disturbances to this process of tissue maintenance: as the creation rate of new cells with long telomeres falls, the average telomere length in tissue will also fall.

Telomerase is vital to most cancers, in which individual cells maintain long lives and act more like unlimited stem cells than the ordinary cells they are descended from. A fair amount of modern research into telomeres and telomerase is conducted by the cancer research community. Ways to selectively block the activity of telomerase would be a potent cancer therapy.

One of the possible reasons why artificially increased levels of telomerase extends life in mice is that it improves stem cell function in this way. Extending telomeres is not the only function of telomerase, however. Evolution tends to produce systems in which components are promiscuously reused in many processes. For example, telomerase has been shown to improve mitochondrial function, and mitochondria are important in the aging process:

Telomerase activity is essential for human cancer cells in order to maintain telomeres and provide unlimited proliferation potential and cellular immortality. However, additional non-telomeric roles emerge for the telomerase protein TERT that can impact tumourigenesis and cancer cell properties. This review summarises our current knowledge of non-telomeric functions of telomerase in human cells, with a special emphasis on cancer cells.

Non-canonical functions of telomerase can be performed within the nucleus as well as in other cellular compartments. These telomere-independent activities of TERT influence various essential cellular processes, such as gene expression, signalling pathways, mitochondrial function as well as cell survival and stress resistance. Emerging data show the interaction of telomerase with intracellular signalling pathways such as NF-κB and WNT/β-catenin; thereby contributing to inflammation, epithelial to mesenchymal transition (EMT) and cancer invasiveness. All these different functions might contribute to tumourigenesis, and have serious consequences for cancer therapies due to increased resistance against damaging agents and prevention of cell death.

In addition, TERT has been detected in non-nuclear locations such as the cytoplasm and mitochondria. Within mitochondria TERT has been shown to decrease ROS generation, improve respiration, bind to mitochondrial DNA, increase mitochondrial membrane potential and interact with mitochondrial tRNAs. All these different non-telomere-related mechanisms might contribute towards the higher resistance of cancer cells against DNA damaging treatments and promote cellular survival. Understanding these different mechanisms and their complexity in cancer cells might help to design more effective cancer therapies in the future.

Link: http://dx.doi.org/10.2174/1381612820666140630095606

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