Affinage

TERT

Telomerase reverse transcriptase · UniProt O14746

Length
1132 aa
Mass
127.0 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TERT is the catalytic reverse transcriptase subunit of telomerase, the ribonucleoprotein enzyme that synthesizes telomeric DNA repeats at chromosome ends, and its expression level is the rate-limiting determinant of telomerase activity during immortalization and tumorigenesis (PMID:9288757, PMID:9528864). TERT directly assembles with the telomerase RNA component to form active enzyme, an interaction that depends on a structured region of the RNA rather than a specific sequence, as established by in vitro reconstitution and RNA-mutagenesis in vertebrate and yeast systems (PMID:11602347, PMID:15314178). Because TERT is normally silenced in somatic cells, its cancer-specific re-expression is achieved chiefly through transcriptional deregulation: recurrent -124C>T and -146C>T promoter mutations create de novo ETS binding motifs and drive monoallelic reactivation, raising TERT mRNA, protein, telomerase activity, and telomere length (PMID:23348506, PMID:23348503, PMID:25722414, PMID:26657580). These mutant promoters are read out by the GABPB1L-isoform GABP complex and by ETS1, coupling oncogenic BRAF and EGFR-AMPK signaling to selective TERT induction and creating a dependence on GABPB1L for tumor growth that is reversible by base-editing the mutation back to wild-type (PMID:31391125, PMID:33758097, PMID:32066906, PMID:36130485). A parallel layer of regulation operates through an activating network and repressive controls: KLF4, the NCOA3-SP1 axis, and MEK/ERK/AP-1 signaling activate TERT, while EBF1 acts as a direct repressor and THOR-region DNA methylation neutralizes repression to upregulate TERT independently of promoter mutation (PMID:30358567, PMID:33239622, PMID:35508454, PMID:38908367, PMID:32364535). Cooperation with the shelterin component TPP1, whose promoter variants co-occur with TERT promoter mutations, is required for productive telomere lengthening (PMID:36356143). Post-transcriptional control further tunes TERT through intron retention that confines transcripts to the nucleus until mitotic splicing and through RBM10-driven exon skipping that switches output toward a nonfunctional isoform (PMID:34083519, PMID:33520366). Beyond telomere synthesis, TERT carries out telomerase-independent functions: it forms an RNA-dependent RNA polymerase complex with RMRP RNA generating Dicer-processed siRNAs (PMID:19701182), transcriptionally activates endogenous retroviruses to trigger RIG-1/MDA5-MAVS interferon and CXCL10 signaling that shapes the tumor immune microenvironment (PMID:35107856), sustains pentose phosphate pathway flux and an Nrf2 regulatory loop (PMID:27148686, PMID:35460557), and acts upstream of DNMT1 and DNMT3B to control DNA methylation and senescence programs (PMID:38908367, PMID:32882013). Rare missense TERT variants in myelodysplastic syndrome impair catalysis, protein-RNA interaction, and telomere recruitment (PMID:34019641).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1998 High

    Established that TERT is itself the rate-limiting catalytic subunit of telomerase rather than a correlated marker, by showing its expression alone reconstitutes enzyme activity.

    Evidence Cloning and expression profiling, then ectopic expression of tagged hTERT with TRAP assays and co-purification in telomerase-negative cells

    PMID:9288757 PMID:9528864

    Open questions at the time
    • Did not define the structural basis of TERT-RNA assembly
    • Did not address how TERT is silenced in somatic cells
  2. 2004 High

    Defined how TERT engages telomerase RNA, showing assembly depends on a structured RNA region rather than specific sequence.

    Evidence In vitro reconstitution of vertebrate TERT with telomerase RNA in reticulocyte lysate, and stem-loop mutagenesis of yeast TLC1 with genetic complementation

    PMID:11602347 PMID:15314178

    Open questions at the time
    • Human TERT-TERC contact map not resolved at atomic level
    • Did not address regulation of human TERT expression
  3. 2015 High

    Identified the dominant mechanism of cancer-specific TERT reactivation, showing hotspot promoter mutations create ETS motifs that monoallelically upregulate telomerase and lengthen telomeres.

    Evidence Cancer genome sequencing, luciferase reporter assays, and a urothelial cell-line panel measuring mRNA, protein, TRAP activity, telomere length, plus allele-specific RNA-seq

    PMID:23348503 PMID:23348506 PMID:25722414 PMID:26657580

    Open questions at the time
    • Monoallelic specificity mechanism not fully explained
    • Which trans-factors read the mutant motif left for later work
  4. 2009 High

    Revealed a telomerase-independent activity by showing TERT forms an RdRP complex with RMRP RNA producing Dicer-processed siRNAs.

    Evidence Co-IP of TERT with RMRP RNA, in vitro RdRP assay, and Dicer-dependent siRNA processing

    PMID:19701182

    Open questions at the time
    • Physiological targets of the siRNAs not defined
    • Relationship to telomerase complex assembly unclear
  5. 2020 High

    Showed which transcription factor complex executes promoter-mutant reactivation and that it is a therapeutic dependency, by linking the GABPB1L-GABP complex and ETS1 to oncogenic signaling and reverting the mutation by base editing.

    Evidence GABPB1L-specific binding and inducible knockdown, ChIP for ETS1, BRAF inhibition, and AAV-delivered adenine base editor in glioma models in vivo

    PMID:31391125 PMID:32066906 PMID:33758097

    Open questions at the time
    • Generality across non-glioma promoter-mutant tumors not fully mapped
    • Long-term safety of base-editing approach untested
  6. 2020 High

    Expanded the transcriptional control network beyond promoter mutations, identifying activators (KLF4, NCOA3-SP1), a direct repressor (EBF1), and THOR methylation as a mutation-independent epigenetic route.

    Evidence ChIP, reporter assays, knockdown/rescue epistasis, large-scale tumor methylation analysis, and in vivo models across HCC, gastric, and lung tissue

    PMID:30358567 PMID:32364535 PMID:33239622 PMID:35508454

    Open questions at the time
    • Hierarchy and combinatorial logic among these factors unresolved
    • Tissue specificity of each control mechanism incompletely defined
  7. 2022 High

    Showed that promoter-mutant TERT upregulation is insufficient alone, requiring cooperative TPP1 upregulation for telomere lengthening.

    Evidence Melanoma genomic sequencing, ACD/TPP1 promoter reporter assays, and telomere length measurement

    PMID:36356143

    Open questions at the time
    • Whether other shelterin components similarly cooperate is unaddressed
    • Mechanism of TERT-TPP1 functional synergy at telomeres not detailed
  8. 2022 Medium

    Defined post-transcriptional control of TERT through nuclear intron retention with mitotic splicing and RBM10-driven exon skipping toward a nonfunctional isoform.

    Evidence Single-molecule RNA FISH, antisense oligonucleotide blocking of intron excision, RNA-IP and pull-down, and telomerase activity assays

    PMID:33520366 PMID:34083519

    Open questions at the time
    • Signals coupling splicing to cell cycle not identified
    • Single-lab findings not independently replicated
  9. 2024 Medium

    Characterized telomerase-independent and downstream metabolic/epigenetic roles of TERT, linking it to PPP flux, an Nrf2 loop, ERV-driven interferon signaling, DNMT control, and senescence suppression.

    Evidence Loss/gain-of-function with telomerase-dead mutants, MRS metabolic imaging, pathway inhibitor epistasis, transcriptomics, and in vivo tumor and aging models

    PMID:27148686 PMID:32882013 PMID:35107856 PMID:35460557 PMID:38908367

    Open questions at the time
    • Direct molecular targets of TERT in these non-canonical roles not defined
    • Mostly single-lab studies with limited cross-validation
  10. 2021 Medium

    Connected TERT to human disease by showing rare missense variants impair catalysis, RNA binding, and telomere recruitment in MDS patients.

    Evidence Cell-based telomere elongation assays across all rare variants and homology modeling of TERT-TPP1

    PMID:34019641

    Open questions at the time
    • Genotype-phenotype correlation in patients not fully established
    • Structural inferences based on homology model rather than experimental structure

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse telomerase-independent functions of TERT (RdRP, ERV/interferon signaling, metabolic and DNMT regulation) are mechanistically integrated with its canonical reverse transcriptase activity and partitioned across subcellular compartments remains unresolved.
  • No unified model linking canonical and non-canonical activities
  • Compartment-specific TERT pools and their distinct partners not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 3 GO:0003723 RNA binding 2 GO:0016740 transferase activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005694 chromosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1430728 Metabolism 2 R-HSA-168256 Immune System 1
Partners
AGO2GABPB1LNCOA3RBM10RMRPSP1TERCTPP1
Complex memberships
TERT-RMRP RdRP complextelomerase holoenzyme

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 hEST2/hTERT (TERT) was identified as the human telomerase catalytic subunit gene based on sequence similarity with lower eukaryote telomerase catalytic subunit genes; its mRNA expression parallels telomerase activity in tumor cells and during immortalization, suggesting it is a rate-limiting determinant of telomerase activity. Molecular cloning, sequence analysis, expression profiling in telomerase-positive vs. negative cell lines and tissues Cell High 9288757
1998 Ectopic expression of epitope-tagged hTERT in telomerase-negative human cells reconstituted telomerase activity to levels comparable to immortal cells, and the expressed hTERT protein co-purified with cellular telomerase activity, establishing hTERT as the rate-limiting catalytic subunit of the telomerase holoenzyme. Ectopic expression of tagged hTERT, telomerase activity assay (TRAP), co-purification of hTERT with telomerase activity Oncogene High 9528864
2001 Xenopus TERT (xTERT) reconstituted active telomerase in vitro when co-expressed with the Xenopus telomerase RNA (xTR) in a cell-free system, confirming that TERT is the catalytic reverse transcriptase subunit that directly assembles with the RNA component to form active telomerase. xTERT expression levels were shown to be the primary mechanism regulating telomerase activity during Xenopus development. In vitro reconstitution of telomerase activity using recombinant xTERT and xTR in rabbit reticulocyte lysate; telomerase activity assays across developmental stages Gene High 11602347
2004 In budding yeast (S. cerevisiae), a specific stem-loop hairpin within the telomerase RNA TLC1 is required for interaction with the Est2 (TERT ortholog) reverse transcriptase protein. Replacement of a 95-nucleotide region required for Est2 interaction with a 39-nucleotide pseudoknot from a distantly related telomerase RNA produced functional telomerase, indicating that Est2 associates with the RNA via a structured region rather than specific sequences. Mutagenesis of TLC1 RNA stem-loop structures; genetic complementation assays for telomere maintenance; RNA-protein interaction studies Molecular and cellular biology High 15314178
2009 Human TERT interacts with RMRP RNA (the RNA component of mitochondrial RNA processing endoribonuclease) to form a distinct ribonucleoprotein complex with RNA-dependent RNA polymerase (RdRP) activity, producing double-stranded RNAs that can be processed into siRNA in a Dicer-dependent manner. This identifies a mammalian RdRP activity for TERT independent of telomere synthesis. Co-immunoprecipitation of TERT with RMRP RNA; in vitro RdRP activity assay; Dicer-dependent siRNA processing assay Nature High 19701182
2013 Recurrent somatic point mutations in the TERT core promoter (-124C>T and -146C>T) in melanoma generate de novo consensus binding motifs for ETS transcription factors and increase transcriptional activity from the TERT promoter by two- to fourfold in reporter assays, providing a mechanism for cancer-specific TERT re-expression. Systematic cancer genome sequencing; luciferase reporter assays of mutant vs. wild-type TERT promoter; ETS motif analysis Science High 23348503 23348506
2015 TERT promoter mutations in urothelial cancer correlate with higher TERT mRNA levels, TERT protein levels, telomerase enzymatic activity, and telomere length compared to wild-type promoter cells, directly linking promoter mutation to functional telomerase upregulation. Analysis of 23 human UC cell lines: TERT mRNA quantification, TERT protein detection, telomerase TRAP assay, telomere length measurement Science High 25722414
2015 TERT promoter mutations lead to monoallelic expression of TERT in human cancer cells; hotspot TERT promoter mutations, without exception, re-activate only one allele as shown by deep RNA sequencing with allele-specific analysis. Deep RNA sequencing with allele-specific variant analysis in human cancer cell lines Oncogenesis Medium 26657580
2016 Nrf2 and TERT form a regulatory loop in glioblastoma: TERT knockdown abrogates Nrf2 levels, while ectopic Nrf2 expression increases TERT expression. TERT inhibition (by drug, siRNA, or dominant-negative TERT) suppresses expression and activity of pentose phosphate pathway enzymes G6PD and Transketolase, and leads to glycogen accumulation, placing TERT as a regulator of metabolic flux. siRNA knockdown, dominant-negative TERT overexpression, pharmacological inhibition (Costunolide), ectopic Nrf2 expression, enzyme activity assays, xenograft mouse model Cell death & disease Medium 27148686
2018 DNA hypermethylation of THOR (a 433-bp region immediately upstream of the TERT core promoter, containing 52 CpG sites) counteracts its repressive function on TERT promoter activity and constitutes a prevalent cancer-associated epigenetic mechanism of TERT upregulation independent of TERT promoter mutations. Reporter assays with methylated/unmethylated THOR constructs; bisulfite sequencing/methylation analysis in 1,352 human tumors; functional promoter activity assays The Journal of clinical investigation High 30358567
2018 AGO2 promotes telomerase activity and stimulates physical association between TERT and TERC; AGO2 depletion results in shorter telomeres and lower proliferation. AGO2 interacts with TERC and a small RNA (terc-sRNA) derived from the H/ACA box of TERC, and overexpression of terc-sRNA alone is sufficient to enhance telomerase activity. Gain- and loss-of-function approaches (AGO2 knockdown/overexpression); Co-IP of AGO2 with TERC; telomerase activity assay; telomere length measurement; in vitro and in vivo proliferation assays EMBO reports Medium 30591524
2019 ETS1 links BRAFV600E oncogenic signaling to TERT promoter activity in double-mutant (BRAFV600E + TERT promoter mutation) glioma: BRAF inhibition reduces ETS1 expression and phosphorylation, decreases TERT promoter activity and TERT expression exclusively in double-mutant cells. ChIP confirmed ETS1 binding to the mutant TERT promoter. qRT-PCR, chromatin immunoprecipitation (ChIP), Western blot, luciferase reporter assays, siRNA knockdown, BRAF inhibitor treatment in glioma cell lines Acta neuropathologica communications Medium 31391125
2020 TERT promoter mutations create binding sites for the GABPB1L-isoform-containing GABP complex; increased binding of this specific complex to the mutant TERT promoter drives TERT reactivation and telomere maintenance. TERT promoter mutant GBM cells exhibit critical dependence on GABPB1L for proliferation, and GABPB1L knockdown combined with temozolomide impairs DNA damage response and reduces GBM tumor growth in vivo. GABPB1L-specific binding assays, GABPB1L knockdown (genetic/inducible), in vivo intracranial GBM tumor growth, combination with temozolomide chemotherapy Proceedings of the National Academy of Sciences of the United States of America High 33758097
2020 CRISPR/Cas9-mediated base editing of the -124C>T TERT promoter mutation back to wild-type -124C blocked ETS family transcription factor binding to the TERT promoter, reduced TERT transcription and protein expression, and induced cancer cell senescence and proliferative arrest; local AAV delivery of the base editor inhibited growth of TERT promoter-mutant gliomas in vivo. Programmable adenine base editing (CjABE), sgRNA-guided CRISPR interference, qRT-PCR for TERT expression, Western blot for TERT protein, senescence assays, in vivo glioma xenograft model with AAV delivery Nature cell biology High 32066906
2020 NCOA3 binds to the TERT promoter at the -234 to -144 region, recruits SP1, and transcriptionally activates TERT expression in hepatocellular carcinoma. NCOA3 knockdown suppresses HCC cell growth and is rescued by TERT overexpression, placing TERT downstream of the NCOA3-SP1 axis. NCOA3 knockdown/overexpression, TERT overexpression rescue, TERT promoter binding assays (ChIP-like), in vitro and in vivo tumor growth assays Cell death & disease Medium 33239622
2020 TERT can transcriptionally activate a subclass of endogenous retroviruses (ERVs) independent of its telomerase activity, generating double-stranded RNAs sensed by the RIG-1/MDA5-MAVS pathway to trigger interferon signaling; TERT-induced ERV/interferon signaling stimulates CXCL10 chemokine expression, promoting infiltration of suppressive T-cell populations (CD4+ and FOXP3+) in tumors. ssGSEA across 9,264 tumor samples; TERT overexpression/knockdown; telomerase-dead TERT mutant; dsRNA detection; RIG-1/MDA5-MAVS pathway analysis; T-cell infiltration analysis EMBO reports Medium 35107856
2021 Nuclear retention of TERT mRNA is driven by intron retention; specific introns are robustly retained in nuclear TERT transcripts (shown by single-molecule RNA FISH), and splicing of these retained introns occurs during mitosis. Blocking intron excision using RNA-targeting thiomorpholino antisense oligonucleotides forces nuclear retention and significantly affects cell viability. Single-molecule RNA FISH, RNA-targeting thiomorpholino antisense oligonucleotides (blocking intron excision), cell viability assays, splicing analysis Nature communications Medium 34083519
2021 RBM10 promotes exclusion of exons 7 and 8 from hTERT pre-mRNA, switching production from full-length active hTERT (hTERT-FL) to a functionless isoform (hTERT-s), thereby suppressing telomerase activity and subsequent telomere shortening. RNA immunoprecipitation and RNA pull-down confirmed direct RBM10-hTERT RNA interaction. RNA immunoprecipitation (RNA-IP), RNA pull-down assay, gain/loss-of-function experiments, telomerase activity assay, xenograft tumor growth assay American journal of cancer research Medium 33520366
2021 Missense TERT rare variants in MDS patients impair domain-specific functions including catalysis, protein-RNA interactions, and recruitment to telomeres, as assessed by a cell-based telomere elongation assay. A homology model of human TERT bound to shelterin protein TPP1 was used to infer structural impact of variants. Cloning of all rare missense variants; cell-based telomere elongation assay; homology structural modeling of TERT-TPP1 interaction Blood Medium 34019641
2022 GABP (specifically the GABPB1L isoform complex) couples EGFR-AMPK oncogenic signaling to TERT expression selectively from the mutant TERT promoter in glioblastoma; proliferation arrest decreases TERT expression in a GABP-dependent manner, and EGFR-AMPK signaling promotes telomerase activity and maintains telomere length. Copy number/mRNA/protein correlation analysis, pharmacologic EGFR inhibition, genetic GABP perturbation, AMPK pathway analysis, telomerase activity assay, telomere length measurement Cell reports Medium 36130485
2022 TPP1 (ACD) promoter variants co-occurring with TERT promoter mutations in melanoma create or modify ETS transcription factor binding sites, increase TPP1 expression, and function together with TERT to synergistically lengthen telomeres, demonstrating that TERT promoter mutation alone is insufficient for telomere maintenance and requires cooperation with TPP1 upregulation. Genomic sequencing of melanoma samples, reporter assays for ACD promoter variants, TPP1/TERT expression analysis, telomere length measurement Science High 36356143
2022 KLF4 directly binds to the TERT promoter region (shown by ChIP) in alveolar epithelial cells and regulates TERT transcription; KLF4 siRNA knockdown reduces TERT expression and telomerase activity, while KLF4 overexpression increases them. In vivo, AAV-mediated KLF4 overexpression in alveolar epithelial cells protects TERT expression and suppresses pulmonary fibrosis. ChIP assay, siRNA knockdown, KLF4 overexpression, telomerase activity assay, AAV-mediated in vivo overexpression in mouse model Cell death & disease Medium 35508454
2024 A TERT activator compound (TAC) upregulates TERT transcription via the MEK/ERK/AP-1 signaling cascade. TAC-induced TERT elevation promotes telomere synthesis and silences p16INK4a expression via upregulation of DNMT3B-mediated promoter hypermethylation, reducing senescence markers, inflammatory cytokines, and neuroinflammation in aged mice while preserving cognitive function. TERT activator compound treatment; MEK/ERK/AP-1 pathway inhibitor epistasis; DNMT3B analysis; telomere synthesis assay; cellular senescence and p16INK4a measurements; in vivo aged mouse model Cell High 38908367
2020 TERT overexpression increases DNMT1 levels and DAC (decitabine) sensitivity via a telomerase-independent mechanism in glioma cells; p21 knockdown leads to TERT upregulation, and DNMT1 RNA inhibition abrogates DAC response in TERT-proficient cells, placing TERT upstream of DNMT1 in a p21-TERT-DNMT1 axis. TERT overexpression, p21 knockdown (siRNA), DNMT1 RNAi, DAC treatment, RNA sequencing, KEGG enrichment analysis Neuro-oncology Medium 32882013
2020 Genomic and epigenomic inactivation of EBF1 (via DNA methylation, dominant-negative mutations, or genomic deletion of EBF1 binding sites near the TERT promoter) de-represses TERT transcription in gastric cancer, identifying EBF1 as a direct TERT transcriptional repressor. Comprehensive genomic and epigenomic analysis of primary GCs; ChIP for EBF1 binding at TERT promoter; reporter assays; EBF1 knockdown/overexpression functional assays in vitro and in vivo The Journal of clinical investigation High 32364535
2021 TERT silencing (directly or via GABPB1 knockdown) in TERT promoter mutant glioblastoma reduces pentose phosphate pathway flux, glucose-6-phosphate dehydrogenase activity, NADPH, lactate production, glycolytic flux, and glutathione levels, defining metabolic consequences of TERT suppression detectable by MRS. TERT and GABPB1 siRNA knockdown, 1H and hyperpolarized 13C MRS metabolic imaging, enzyme activity assays (G6PD), NADPH/NADH measurement, in vivo tumor imaging Neuro-oncology Medium 35460557

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell 1596 9288757
2013 Highly recurrent TERT promoter mutations in human melanoma. Science (New York, N.Y.) 1481 23348506
2013 TERT promoter mutations in familial and sporadic melanoma. Science (New York, N.Y.) 1470 23348503
1998 Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase. Oncogene 356 9528864
2016 TERT promoter mutations in thyroid cancer. Endocrine-related cancer 346 26733501
2009 An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA. Nature 309 19701182
2015 Cancer. TERT promoter mutations and telomerase reactivation in urothelial cancer. Science (New York, N.Y.) 265 25722414
2016 Understanding TERT Promoter Mutations: A Common Path to Immortality. Molecular cancer research : MCR 240 26941407
2020 TERT-Regulation and Roles in Cancer Formation. Frontiers in immunology 232 33329574
2013 TERT promoter mutations in cancer development. Current opinion in genetics & development 191 24657534
2016 TERT promoter mutations in telomere biology. Mutation research. Reviews in mutation research 157 28342451
2018 DNA hypermethylation within TERT promoter upregulates TERT expression in cancer. The Journal of clinical investigation 145 30358567
2018 The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma. Nature communications 136 29802247
2020 Programmable base editing of mutated TERT promoter inhibits brain tumour growth. Nature cell biology 127 32066906
2016 Cancer-Specific Telomerase Reverse Transcriptase (TERT) Promoter Mutations: Biological and Clinical Implications. Genes 111 27438857
2007 Chemoprotective and carcinogenic effects of tert-butylhydroquinone and its metabolites. Current drug metabolism 108 17266519
2016 Nrf2-driven TERT regulates pentose phosphate pathway in glioblastoma. Cell death & disease 98 27148686
2014 Concurrent alterations in TERT, KDM6A, and the BRCA pathway in bladder cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 97 25225064
2010 Variation at the TERT locus and predisposition for cancer. Expert reviews in molecular medicine 93 20478107
2021 TERT Promoter Alterations in Glioblastoma: A Systematic Review. Cancers 83 33800183
2024 The regulations of telomerase reverse transcriptase (TERT) in cancer. Cell death & disease 82 38278800
2015 Mutations in TERT promoter and FGFR3 and telomere length in bladder cancer. International journal of cancer 82 25809917
2017 New Molecular Considerations for Glioma: IDH, ATRX, BRAF, TERT, H3 K27M. Current neurology and neuroscience reports 81 28271343
2015 TERT promoter mutations and monoallelic activation of TERT in cancer. Oncogenesis 80 26657580
1986 Toxicology of tert-butylhydroquinone (TBHQ). Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 78 3542758
2019 TERT gene: its function and dysregulation in cancer. Journal of clinical pathology 77 30696697
2004 Microbial degradation of methyl tert-butyl ether and tert-butyl alcohol in the subsurface. Journal of contaminant hydrology 77 15134874
2015 TERT promoter mutations in primary liver tumors. Clinics and research in hepatology and gastroenterology 76 26336998
2024 TERT activation targets DNA methylation and multiple aging hallmarks. Cell 71 38908367
2017 TERT biology and function in cancer: beyond immortalisation. Journal of molecular endocrinology 68 28057768
2013 Overexpression and promoter mutation of the TERT gene in malignant pleural mesothelioma. Oncogene 66 23975423
2017 Transcriptional Regulation of Telomerase Reverse Transcriptase (TERT) by MYC. Frontiers in cell and developmental biology 65 28184371
2015 Association of TERT Promoter Mutation, But Not BRAF Mutation, With Increased Mortality in PTC. The Journal of clinical endocrinology and metabolism 61 26461266
2018 Implications of TERT promoter mutations and telomerase activity in urothelial carcinogenesis. Nature reviews. Urology 60 29599449
2016 TERT Promoter Mutations in Thyroid Cancer. Hormones & cancer 59 26902827
2020 TERT promoter mutations and telomeres during tumorigenesis. Current opinion in genetics & development 57 32163830
2019 Telomerase Reverse Transcriptase (TERT) in Action: Cross-Talking with Epigenetics. International journal of molecular sciences 55 31284662
2018 TERT promoter mutations in solitary fibrous tumour. Histopathology 54 29985536
2017 TERT structural rearrangements in metastatic pheochromocytomas. Endocrine-related cancer 52 28974544
2020 Correlation between IDH, ATRX, and TERT promoter mutations in glioma. Brain tumor pathology 51 32227259
2020 Telomerase Reverse Transcriptase (TERT) Regulation in Thyroid Cancer: A Review. Frontiers in endocrinology 50 32849278
2020 The Solo Play of TERT Promoter Mutations. Cells 47 32204305
2015 Molecular background of oligodendroglioma: 1p/19q, IDH, TERT, CIC and FUBP1. CNS oncology 47 26545048
2021 Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA is driven by intron retention. Nature communications 45 34083519
2021 Cancer-specific loss of TERT activation sensitizes glioblastoma to DNA damage. Proceedings of the National Academy of Sciences of the United States of America 44 33758097
2018 Exploiting TERT dependency as a therapeutic strategy for NRAS-mutant melanoma. Oncogene 44 29695835
2014 TERT promoter mutations and gene amplification: promoting TERT expression in Merkel cell carcinoma. Oncotarget 43 25301727
2022 TERT activates endogenous retroviruses to promote an immunosuppressive tumour microenvironment. EMBO reports 42 35107856
2021 The clinical and functional effects of TERT variants in myelodysplastic syndrome. Blood 42 34019641
2004 Structural elements required for association of the Saccharomyces cerevisiae telomerase RNA with the Est2 reverse transcriptase. Molecular and cellular biology 41 15314178
2022 TERT Promoter Mutations and Telomerase in Melanoma. Journal of oncology 40 35903534
2020 TERT promoter mutations and GABP transcription factors in carcinogenesis: More foes than friends. Cancer letters 39 32768523
2022 KLF4 regulates TERT expression in alveolar epithelial cells in pulmonary fibrosis. Cell death & disease 38 35508454
2020 BRAF and TERT promoter mutations: clinical application in thyroid cancer. Endocrine journal 38 32321884
2007 Expansion and Harvesting of hMSC-TERT. The open biomedical engineering journal 37 19662126
2020 TERT, a promoter of CNS malignancies. Neuro-oncology advances 35 32226942
2014 TERT promoter mutation is uncommon in acral lentiginous melanoma. Journal of cutaneous pathology 35 24588324
2017 TERT promoter hotspot mutations in breast cancer. Breast cancer (Tokyo, Japan) 34 29222734
2020 Fisetin Promotes Hair Growth by Augmenting TERT Expression. Frontiers in cell and developmental biology 33 33178686
2021 TERT and DNMT1 expression predict sensitivity to decitabine in gliomas. Neuro-oncology 31 32882013
2021 Significance of TERT Genetic Alterations and Telomere Length in Hepatocellular Carcinoma. Cancers 31 33946181
2019 TERT expression is susceptible to BRAF and ETS-factor inhibition in BRAFV600E/TERT promoter double-mutated glioma. Acta neuropathologica communications 31 31391125
2020 CRISPR/Cas9-Mediated TERT Disruption in Cancer Cells. International journal of molecular sciences 30 31963842
2019 MED12, TERT and RARA in fibroepithelial tumours of the breast. Journal of clinical pathology 30 31662438
2017 Thoracic radiotherapy (TRT) improved survival in both oligo- and polymetastatic extensive stage small cell lung cancer. Scientific reports 30 28835666
2023 TERT Extra-Telomeric Roles: Antioxidant Activity and Mitochondrial Protection. International journal of molecular sciences 29 36901881
2023 TERT promoter mutations in thyroid cancer. Endocrine journal 29 37532521
2022 TPP1 promoter mutations cooperate with TERT promoter mutations to lengthen telomeres in melanoma. Science (New York, N.Y.) 29 36356143
2021 Autophagy, TERT, and mitochondrial dysfunction in hyperoxia. American journal of physiology. Heart and circulatory physiology 29 34559580
2001 Identification and analyses of the Xenopus TERT gene that encodes the catalytic subunit of telomerase. Gene 29 11602347
2018 TERT promoter methylation is significantly associated with TERT upregulation and disease progression in pituitary adenomas. Journal of neuro-oncology 27 30392088
2016 High incidence of TERT mutation in brain tumor cell lines. Brain tumor pathology 27 26960334
2016 TRT, a Vertebrate and Protozoan Tc1-Like Transposon: Current Activity and Horizontal Transfer. Genome biology and evolution 27 27667131
2016 Acquired TERT promoter mutations stimulate TERT transcription in mantle cell lymphoma. American journal of hematology 26 26852175
2021 Occurrence, functionality and abundance of the TERT promoter mutations. International journal of cancer 24 34313327
2012 TERT's role in colorectal carcinogenesis. Molecular carcinogenesis 24 22351525
2022 Expression of Cellular and Extracellular TERRA, TERC and TERT in Hepatocellular Carcinoma. International journal of molecular sciences 23 35682861
2020 Expression of tert Prevents ALT in Zebrafish Brain Tumors. Frontiers in cell and developmental biology 23 32117990
2021 Tert-butylhydroquinone attenuates osteoarthritis by protecting chondrocytes and inhibiting macrophage polarization. Bone & joint research 22 34724799
2017 Altered TERT promoter and other genomic regulatory elements: occurrence and impact. International journal of cancer 22 28407294
2020 Genomic and epigenomic EBF1 alterations modulate TERT expression in gastric cancer. The Journal of clinical investigation 21 32364535
2020 Targeting the NCOA3-SP1-TERT axis for tumor growth in hepatocellular carcinoma. Cell death & disease 21 33239622
2019 Classifying Melanoma by TERT Promoter Mutational Status. The Journal of investigative dermatology 21 31425705
2016 Association mapping of caffeine content with TCS1 in tea plant and its related species. Plant physiology and biochemistry : PPB 21 27116373
2018 AGO2 promotes telomerase activity and interaction between the telomerase components TERT and TERC. EMBO reports 20 30591524
2022 GABP couples oncogene signaling to telomere regulation in TERT promoter mutant cancer. Cell reports 19 36130485
2021 Clinical Application of TERT Promoter Mutations in Urothelial Carcinoma. Frontiers in oncology 18 34395278
2020 Interplay between TERT promoter mutations and methylation culminates in chromatin accessibility and TERT expression. PloS one 18 32267900
2018 Elevated TERT Expression in TERT-Wildtype Adult Diffuse Gliomas: Histological Evaluation with a Novel TERT-Specific Antibody. BioMed research international 18 29693015
2015 HMGA2 expression pattern and TERT mutations in tumors of the vulva. Oncology reports 18 25823555
2024 TERT Promoter Mutations Frequency Across Race, Sex, and Cancer Type. The oncologist 17 37462445
2022 Imaging biomarkers of TERT or GABPB1 silencing in TERT-positive glioblastoma. Neuro-oncology 17 35460557
2022 Understanding and managing the suppression of spermatogenesis caused by testosterone replacement therapy (TRT) and anabolic-androgenic steroids (AAS). Therapeutic advances in urology 17 35783920
2022 Melatonin alleviates alcoholic liver disease via EGFR-BRG1-TERT axis regulation. Acta pharmaceutica Sinica. B 17 36815038
2006 Alicyclobacillus acidocaldarius thermophilic esterase EST2's activity in milk and cheese models. Applied and environmental microbiology 17 16672457
2024 Whole tumor analysis reveals early origin of the TERT promoter mutation and intercellular heterogeneity in TERT expression. Neuro-oncology 16 38141254
2021 RBM10 regulates human TERT gene splicing and inhibits pancreatic cancer progression. American journal of cancer research 16 33520366
2021 TERT Gene Fusions Characterize a Subset of Metastatic Leydig Cell Tumors. Clinical genitourinary cancer 16 33741265
2020 Mechanisms of TERT Reactivation and Its Interaction with BRAFV600E. Endocrinology and metabolism (Seoul, Korea) 16 32981294
2017 TERT Promoter Hypermethylation in Gastrointestinal Cancer: A Potential Stool Biomarker. The oncologist 16 28754720

Missed literature

Know a paper Affinage missed for TERT? Flag it for the maintainers and the community.

No submissions yet.