[Molecular mechanisms involved in the regulation of telomerase activity]

The main components of telomerase include RNA subunit, hTERT catalytic subunit and hTEP1 regulatory protein. While telomerase plays an important role in maintenance of telomere structural stability, telomere is also involved in the regulation of telomerase activity. Some anticancer drugs inhibit the telomerase activity by breaking the structure of telomere. Activation of human telomerase requires de novo transcription of hTERT gene and correct incorporation of all subunits into holoenzyme. The expression of telomerase activity is likely to be regulated at multiple levels. Firstly, the expression and transcription of the hTERT gene is regulated by various factors; Secondly, various oncogenes and tumor suppressor genes are involved in regulation of telomerase activity by protein-protein interaction with telomere and telomerase proteins directly or indirectly. Thirdly, phosphorylation of hTERT and hTEP1 by protein kinase leads to significant up-regulation of telomerase activity, and conversely, the dephosphorylation result in down-regulation of telomerase activity.