Transcriptional Regulation of Telomerase Activity: Roles of the the Ets Transcription Factor Family

Telomerase maintains telomeres to preclude cell senescence. It remains elusive how telomerase activity is repressed in differentiated cells, but retained at high levels in stem cells and cancer. Recent studies suggest that the Ets transcription factor family, downstream of the mitogen signaling pathways of MAP kinase, regulates telomerase activity at the gene transcription level of human telomerase reverse transcriptase (hTERT). Several Ets transcription factors are involved in regulating hTERT gene expression, both directly and indirectly through the proto-oncogene c-myc. ER81 may mediate telomerase activation in telomerase-negative fibroblasts stimulated by oncogenes Her2/Neu, Ras, and Raf. Ets2 may also play an important role in regulating the hTERT gene; but further studies are required to decipher the mechanisms in the regulation of telomerase activity.