FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W99499757> ?p ?o ?g. }

• W99499757 abstract "Author(s): Gazzaniga, Francesca Smylie | Advisor(s): Blackburn, Elizabeth H; Verdin, Eric | Abstract: Telomerase is a ribonucleoprotein that adds telomeric DNA to the ends of linear chromosomes. It is composed of two core components, the reverse transcriptase component, hTERT, and the RNA template, hTR. In the absence of sufficient telomerase, most differentiated cells experience telomere shortening with each cell division and eventually undergo replicative senescence. Conversely, stem cells and the majority of cancer cells have high telomerase activity, which maintains telomere length allowing them to divide indefinitely. While the role of telomerase in telomere maintenance is clear, recent studies have suggested non-canonical roles for telomerase. The purpose of this thesis is to investigate any non-canonical roles for telomerase in both normal and cancer cells. The first part of this thesis focuses on the role of telomerase in primary human T cells. T cells are one of the few types of differentiated cells that upregulate telomerase activity upon stimulation. While telomerase activity and T cell proliferation correlate, it is unknown if this upregulation is necessary or even quantitatively coupled to T cell survival. Suprisingly, I find that the telomerase RNA, hTR, actually protects CD4+ T cells from apoptosis independent of telomere maintenance or telomerase activity. This is the first report showing a non-telomere role for the telomerase RNA. The second part of this thesis investigates a controversial mechanism for a non-canonical role for hTERT in Wnt signaling. One study published that telomerase activity promotes Wnt/β-catenin signaling in mice and HeLa cells. However, another study was unable to reproduce these findings in mice, but did not investigate these findings in cancer cells. Since Wnt signaling is often dysregulated in breast cancer, we sought to determine if we could independently replicate any hTERT -Wnt/β-catenin interactions in breast cancer cells. Using genetic, biochemical, and bioinformatic analyses we do not find any data supporting the hypothesis that hTERT promotes Wnt/β-catenin signaling in breast cancer cells and instead suggest that any published interactions detected are cell line and cell context specific. We and others have shown hTERT can promote proliferation, protect from apoptosis, and promote mitochondrial function independent of telomere maintenance and/or telomerase activity in a wide variety of cell types. This thesis shows that hTERT does not promote these functions through Wnt/β-catenin signaling. Furthermore, I show for the first time that hTR also has a non-telomere and non-telomerase role protecting from apoptosis in CD4+ T cells. While the importance of telomerase for maintaining telomeres is clear, this thesis shows that both of the telomerase core components have non-canonical roles in cell survival in normal and cancer cells." @default.
• W99499757 created "2016-06-24" @default.
• W99499757 creator A5080944631 @default.
• W99499757 date "2013-01-01" @default.
• W99499757 modified "2023-09-27" @default.
• W99499757 title "Non-canonical roles for telomerase in T cells and breast cancer cells" @default.
• W99499757 hasPublicationYear "2013" @default.
• W99499757 type Work @default.
• W99499757 sameAs 99499757 @default.
• W99499757 citedByCount "0" @default.
• W99499757 crossrefType "journal-article" @default.
• W99499757 hasAuthorship W99499757A5080944631 @default.
• W99499757 hasConcept C104317684 @default.
• W99499757 hasConcept C121608353 @default.
• W99499757 hasConcept C125593758 @default.
• W99499757 hasConcept C137620995 @default.
• W99499757 hasConcept C1491633281 @default.
• W99499757 hasConcept C153911025 @default.
• W99499757 hasConcept C177336024 @default.
• W99499757 hasConcept C2777366897 @default.
• W99499757 hasConcept C34558173 @default.
• W99499757 hasConcept C502942594 @default.
• W99499757 hasConcept C54355233 @default.
• W99499757 hasConcept C552990157 @default.
• W99499757 hasConcept C62478195 @default.
• W99499757 hasConcept C67705224 @default.
• W99499757 hasConcept C75934600 @default.
• W99499757 hasConcept C86803240 @default.
• W99499757 hasConcept C94581717 @default.
• W99499757 hasConcept C95444343 @default.
• W99499757 hasConcept C96232424 @default.
• W99499757 hasConceptScore W99499757C104317684 @default.
• W99499757 hasConceptScore W99499757C121608353 @default.
• W99499757 hasConceptScore W99499757C125593758 @default.
• W99499757 hasConceptScore W99499757C137620995 @default.
• W99499757 hasConceptScore W99499757C1491633281 @default.
• W99499757 hasConceptScore W99499757C153911025 @default.
• W99499757 hasConceptScore W99499757C177336024 @default.
• W99499757 hasConceptScore W99499757C2777366897 @default.
• W99499757 hasConceptScore W99499757C34558173 @default.
• W99499757 hasConceptScore W99499757C502942594 @default.
• W99499757 hasConceptScore W99499757C54355233 @default.
• W99499757 hasConceptScore W99499757C552990157 @default.
• W99499757 hasConceptScore W99499757C62478195 @default.
• W99499757 hasConceptScore W99499757C67705224 @default.
• W99499757 hasConceptScore W99499757C75934600 @default.
• W99499757 hasConceptScore W99499757C86803240 @default.
• W99499757 hasConceptScore W99499757C94581717 @default.
• W99499757 hasConceptScore W99499757C95444343 @default.
• W99499757 hasConceptScore W99499757C96232424 @default.
• W99499757 hasLocation W994997571 @default.
• W99499757 hasOpenAccess W99499757 @default.
• W99499757 hasPrimaryLocation W994997571 @default.
• W99499757 hasRelatedWork W1496772673 @default.
• W99499757 hasRelatedWork W1552706275 @default.
• W99499757 hasRelatedWork W170980041 @default.
• W99499757 hasRelatedWork W176813292 @default.
• W99499757 hasRelatedWork W1966087162 @default.
• W99499757 hasRelatedWork W2004629447 @default.
• W99499757 hasRelatedWork W2014977656 @default.
• W99499757 hasRelatedWork W2078280108 @default.
• W99499757 hasRelatedWork W2139677387 @default.
• W99499757 hasRelatedWork W2167102349 @default.
• W99499757 hasRelatedWork W2317941288 @default.
• W99499757 hasRelatedWork W2325190661 @default.
• W99499757 hasRelatedWork W2410112655 @default.
• W99499757 hasRelatedWork W2440582319 @default.
• W99499757 hasRelatedWork W2495880529 @default.
• W99499757 hasRelatedWork W2550330885 @default.
• W99499757 hasRelatedWork W2594118695 @default.
• W99499757 hasRelatedWork W2791861534 @default.
• W99499757 hasRelatedWork W2802494509 @default.
• W99499757 hasRelatedWork W3122261276 @default.
• W99499757 isParatext "false" @default.
• W99499757 isRetracted "false" @default.
• W99499757 magId "99499757" @default.
• W99499757 workType "article" @default.