Telomerase reverse transcriptase promoter (TERT promoter) (TERT promoter)

The Telomerase reverse transcriptase (TERT) promoter is a critical regulatory DNA sequence that controls the expression of the TERT gene, the catalytic component of the telomerase enzyme (Heidenreich & Kumar, 2017). In most healthy somatic cells, this promoter is epigenetically silenced, leading to telomere shortening and eventual cellular senescence. However, in approximately 90% of human cancers, the TERT promoter is reactivated, most commonly through highly specific somatic mutations (C228T and C250T) that create new binding sites for Ets transcription factors like GABP (Bell et al., 2015). This reactivation provides cancer cells with replicative immortality by maintaining telomere length, a hallmark of oncogenesis. Because these mutations are prevalent in aggressive tumors such as glioblastoma, melanoma, and bladder cancer, but absent in normal tissues, the TERT promoter is a highly specific therapeutic target (Vinagre et al., 2013). Current pharmacological strategies include small molecules designed to stabilize G-quadruplex structures in the promoter to block transcription, as well as experimental genetic interventions like CRISPR-mediated silencing and antisense oligonucleotides (Song et al., 2019).

Other names

hTERT promoterTERTpTelomerase reverse transcriptase gene promoter

Inhibition of TERT transcription through G-quadruplex stabilization or disruption of transcription factor binding sites (e.g., GABP).