Human telomerase reverse transcriptase promoter (hTERT promoter) (hTERT promoter)

The human telomerase reverse transcriptase (hTERT) promoter is the primary regulatory region controlling the expression of the catalytic subunit of telomerase, an enzyme essential for maintaining telomere length. In most adult somatic cells, this promoter is transcriptionally repressed, leading to progressive telomere shortening and eventual replicative senescence (Heidenreich & Kumar, 2017, PMID: 28651081). However, the hTERT promoter is reactivated in approximately 90% of human cancers, often through specific somatic mutations (notably C228T and C250T) that create new binding sites for Ets transcription factors, thereby conferring cellular immortality (Bell et al., 2015, PMID: 25977370). This cancer-specific activity makes the hTERT promoter a highly attractive target for oncology. Therapeutic strategies include using the promoter to drive the selective expression of oncolytic viruses, such as OBP-301 (Telomelysin), or suicide genes specifically within malignant cells (Huang et al., 2020, PMID: 32451431). Additionally, the promoter contains G-rich sequences that can form G-quadruplex structures; small molecules like CX-5461 are being investigated for their ability to stabilize these structures, thereby physically blocking transcription and inducing apoptosis in telomerase-dependent tumors (Song et al., 2019, PMID: 31110140).

Other names

TERT promoterhTERT regulatory regionTelomerase reverse transcriptase promoterhTERT 5-prime regulatory region

Transcriptional inhibition via G-quadruplex stabilization; Cancer-specific promoter-driven viral replication (oncolytic virotherapy); Selective expression of therapeutic suicide genes; Interference with transcription factor binding (e.g., GABP).