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Telomerase reverse transcriptase promotes stem cell competition through MYC

ABSTRACT: Telomerase reverse transcriptase promotes stem cell competition through MYC

PROVIDER: PRJNA607813 | ENA |

REPOSITORIES: ENA

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Mass spectrum for identifying the interacting proteins of telomerase reverse transcriptase

Project description:The 293T cells overexpressing human telomerase reverse transcriptase (hTERT) were lysed and co-immunoprecipitation was performed using hTERT antibody. Then protein mass spectrum was conducted in order to identify the hTERT-interacting proteins.

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Evolutionarily conserved role of Telomerase reverse transcriptase (TERT) in programming the microenvironment via regulation of cGAS/STING pathway

Project description:Telomerase holoenzyme plays a critical role in maintaining telomere length, and thus in regulating inflammation caused by telomeric DNA damage. However, beyond its role in telomere maintenance, the molecular function of telomerase in directly regulating inflammation remains unclear. Here, we show that the reverse transcriptase component of telomerase, TERT, has a cell-type-specific role in directly regulating inflammation via the cytoplasmic cGAS-STING nucleic acid-sensing pathway. Analyses of murine and zebrafish models of gut inflammation and human colitis/Crohn’s patients document that this function of TERT is evolutionarily conserved. Using our novel knock-in TERTVAA mouse model where reverse-transcriptase-inactive TERT is driven by its endogenous loci, and molecular, pharmacological and single-cell approaches we identify the myeloid subpopulation, termed T-MAC, wherein TERT enhances STING activation and initiates type-1 interferon responses independent of reverse transcriptase activity or telomere length. We highlight a hitherto unappreciated role of TERT in directly regulating inflammation and provide a therapeutic rationale for targeting TERT beyond cancers.

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Telomerase reverse transcriptase promotes stem cell competition through MYC

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-07-11 | GSE145659 | GEO

MST-312: a telomerase inhibitor effectively blocking MYC oncogenic functions [array]

Project description:Reactivation of the telomerase reverse transcriptase subunit, TERT, is linked to tumourigenesis due to well-documented telomere-dependent and independent functions. The aim of this study was to investigate the effect of the telomerase inhibitor, MST-312, on TERT functions, focusing in particular, on its effects on MYC stabilty and MYC-regulated pathways, in order to assess its potential as a therapeutic agent. We demonstrate that MST-312 reduces MYC levels in cancer cells, leading to reduced MYC levels on chromatin, and subsequently affecting the MYC-regulated transcriptional program. As a result, MST-312 treatment increases the survival of lymphoma-bearing mice. Mechanistically, MST-312 affects the conformation of TERT, leading to TERT/Terc dissociation, and the subsequent loss of both its telomere-dependent and independent functions. Based on the presented data, we conclude that MST-312 treatment is a promising therapeutic strategy, in particular, in MYC-driven tumorus.

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MST-312: a telomerase inhibitor effectively blocking MYC oncogenic functions [ChIP-Seq]

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Non-canonical Telomerase Reverse Transcriptase Controls Osteogenic Reprogramming of Aortic Valve Cells Through STAT5

Project description:Non-canonical Telomerase Reverse Transcriptase Controls Osteogenic Reprogramming of Aortic Valve Cells Through STAT5

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