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• W2949095601 abstract "Telomerase is a ribonucleoprotein complex responsible for immortalizing 85% of all human malignant tumors, making telomerase regulation a very attractive target for the development of anti-cancer therapeutics. Thus far, many proteins have been identified that regulate human telomerase biogenesis, activity, trafficking, recruitment and degradation. By comparison, there have been very few proteins identified to associate with mouse telomerase. Due to the importance of mouse models in the development of anti-cancer therapeutics, investigation of mouse telomerase-associated proteins is required to establish a detailed understanding of the species-specific differences between mouse and human telomerases and telomeres. Moreover, understanding telomerase and telomere regulation in mouse and human cells may inform us regarding the differential response to telomerase inhibition and telomere dysfunction that has been observed between human and mouse cells. In search for novel proteins associated with mouse telomerase reverse transcriptase (mTERT), the catalytic subunit of telomerase, we introduced an expression vector encoding a dually-tagged Protein G and streptavidin binding peptide (SBP)-mTERT in NIH3T3 cells and we performed SBP-mediated telomerase purification followed by mass spectrometry. We identified the Ewing's sarcoma protein (EWS) as a putative telomerase-associated candidate. We validated the interaction between EWS and human TERT (hTERT) and report that EWS indirectly binds to the active telomerase under physiological levels of hTERT and EWS, and this interaction is not dependent on human telomerase RNA (hTR), DNA, or RNA. Moreover, we present preliminary evidence suggesting that EWS may also directly bind hTR. Finally, we show that knockdown of EWS in HeLa cells does not affect cell growth, but it remains possible that EWS may be a negative regulator of telomerase and telomere length.%%%%La telomerase est un complexe ribonucleoproteique responsable de l'immortalisation de 85% des tumeurs malignes humaines, faisant de sa regulation une excellente cible pour le developpement de traitements contre le cancer. A ce jour ont ete identifiees de nombreuses proteines regulant la biogenese, le transport, l'activite, le recrutement et la degradation de la telomerase humaine. A titre de comparaison, peu de proteines ont ete identifiees comme associees a la telomerase murine. Mais en raison de l'importance des modeles murins dans le developpement de traitements du cancer, la recherche de telles proteines murines est requise pour une comprehension detaillee des differences inter-especes des telomerases et des telomeres humains et murins. De plus, le decryptage de la telomerase et de la regulation des telomeres chez l'homme et la souris nous permettra de mieux apprecier les differences de reponse a l'inhibition et a la dysfonction telomerique observees entre les cellules des deux especes. Afin de trouver de nouvelles proteines associees a la sous-unite catalytique de la telomerase murine, la transcriptase-inverse…" @default.
• W2949095601 created "2019-06-27" @default.
• W2949095601 creator A5030708624 @default.
• W2949095601 date "2014-01-01" @default.
• W2949095601 modified "2023-09-27" @default.
• W2949095601 title "The identification and characterization of EWS as a telomerase-associated protein" @default.
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