human Telomerase Reverse Transcriptase promoter DNA (hTERT promoter)

The human Telomerase Reverse Transcriptase (hTERT) promoter DNA is a critical regulatory region of the TERT gene, which encodes the catalytic subunit of the telomerase enzyme [11, 21]. In normal somatic cells, this promoter is typically silenced, leading to progressive telomere shortening and eventual replicative senescence [13, 14]. However, in approximately 90% of human cancers, the hTERT promoter is reactivated through mechanisms such as highly recurrent hotspot mutations (C228T and C250T) or epigenetic modifications, enabling limitless cellular proliferation and immortality [5, 17]. These mutations create de novo binding sites for transcription factors like ETS, which drive aberrant hTERT expression and telomerase activity [5, 19]. Therapeutically, the hTERT promoter is targeted using small molecules designed to stabilize its unique G-quadruplex (G4) structures, which physically impede the transcriptional machinery and downregulate telomerase expression [1, 4, 7]. Additionally, the cancer-specific activity of the promoter is exploited in gene therapy and oncolytic virotherapy, where it serves as a selective switch to drive the expression of cytotoxic genes or viral replication exclusively within malignant cells [8, 10, 22]. Despite its potential as a universal cancer target, therapeutic challenges include achieving high selectivity over other genomic G-quadruplexes and avoiding toxicity in healthy telomerase-positive populations, such as hematopoietic stem cells [1, 8, 11].

Other names

TERT promoterhTERT core promoterTERTphTERT 5-regulatory regionTelomerase reverse transcriptase promoter

Stabilization of G-quadruplex structures to inhibit transcription; utilization as a tumor-specific promoter for gene therapy and oncolytic viral replication.